Nivolumab With or Without Ipilimumab in Advanced Metastatic Cancer

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ClinicalTrials.gov Identifier: NCT03651271

Recruitment Status : Completed

First Posted : August 29, 2018

Results First Posted : January 17, 2024

Last Update Posted : February 7, 2024

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Sponsor:

Collaborators:

Bristol-Myers Squibb

Cancer Research Institute, New York City

Information provided by (Responsible Party):

Parker Institute for Cancer Immunotherapy

Study Type	Interventional
Study Design	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Advanced Metastatic Cancer Advanced Prostate Cancer
Interventions	Biological: Nivolumab Monotherapy Biological: Nivolumab and Ipilimumab and Combination for Metastatic Cancer Biological: Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer Biological: Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer
Enrollment	100

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At the occurrence of disease progression (PD), participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV every 3 weeks (Q3W). Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV every 4 weeks (Q4W) until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
Period Title: Overall Study
Started	7	72	1	5	15
Completed	1	13	1	1	8
Not Completed	6	59	0	4	7
Reason Not Completed
Death	4	37	0	2	6
Lost to Follow-up	1	5	0	1	0
Physician Decision	0	2	0	0	0
Withdrawal by Subject	1	15	0	0	1
Patient medically unable to continue	0	0	0	1	0

Baseline Characteristics

Arm/Group Title		"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B	Total
Arm/Group Description		Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Total of all reporting groups
Arm/Group Description		Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.	Total of all reporting groups
Overall Number of Baseline Participants		7	72	1	5	15	100
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	72 participants	1 participants	5 participants	15 participants	100 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	6 85.7%	46 63.9%	0 0.0%	1 20.0%	4 26.7%	57 57.0%
	>=65 years	1 14.3%	26 36.1%	1 100.0%	4 80.0%	11 73.3%	43 43.0%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	72 participants	1 participants	5 participants	15 participants	100 participants
	Female	1 14.3%	35 48.6%	0 0.0%	0 0.0%	0 0.0%	36 36.0%
	Male	6 85.7%	37 51.4%	1 100.0%	5 100.0%	15 100.0%	64 64.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	72 participants	1 participants	5 participants	15 participants	100 participants
	Hispanic or Latino	0 0.0%	9 12.5%	0 0.0%	0 0.0%	0 0.0%	9 9.0%
	Not Hispanic or Latino	7 100.0%	63 87.5%	1 100.0%	5 100.0%	15 100.0%	91 91.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	72 participants	1 participants	5 participants	15 participants	100 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	5 6.9%	0 0.0%	0 0.0%	0 0.0%	5 5.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	7 9.7%	0 0.0%	1 20.0%	1 6.7%	9 9.0%
	White	6 85.7%	45 62.5%	1 100.0%	3 60.0%	14 93.3%	69 69.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	1 14.3%	15 20.8%	0 0.0%	1 20.0%	0 0.0%	17 17.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	7 participants	72 participants	1 participants	5 participants	15 participants	100 participants
United States		7	72	1	5	15	100
Eastern Cooperative Oncology Group (ECOG) Performance Score ^[1] [2] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	70 participants	1 participants	5 participants	15 participants	98 participants
	0	4 57.1%	23 32.9%	0 0.0%	0 0.0%	4 26.7%	31 31.6%
	1	3 42.9%	47 67.1%	1 100.0%	5 100.0%	11 73.3%	67 68.4%
		[1] Measure Description: The Eastern Cooperative Oncology Group (ECOG) performance status is a widely-used scale to assess how a patient's disease is progressing, assess how the disease affects the daily living abilities of the patient, and determine the appropriate treatment and prognosis. Here is a brief description of the ECOG performance status: 0: Fully active, able to carry on all pre-disease performance without restriction. 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework or office work. [2] Measure Analysis Population Description: Two participants did not have an ECOG performance score recorded at Screening and are excluded from analysis.
Primary Tumor Type ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	72 participants	1 participants	5 participants	15 participants	100 participants
	Prostate	0 0.0%	12 16.7%	1 100.0%	5 100.0%	15 100.0%	33 33.0%
	Head and Neck	3 42.9%	6 8.3%	0 0.0%	0 0.0%	0 0.0%	9 9.0%
	Colorectal	0 0.0%	7 9.7%	0 0.0%	0 0.0%	0 0.0%	7 7.0%
	Sarcoma	0 0.0%	7 9.7%	0 0.0%	0 0.0%	0 0.0%	7 7.0%
	Ovarian	1 14.3%	5 6.9%	0 0.0%	0 0.0%	0 0.0%	6 6.0%
	Uterine	0 0.0%	4 5.6%	0 0.0%	0 0.0%	0 0.0%	4 4.0%
	Breast	0 0.0%	3 4.2%	0 0.0%	0 0.0%	0 0.0%	3 3.0%
	Hepatocellular cholangiocarcinoma	0 0.0%	3 4.2%	0 0.0%	0 0.0%	0 0.0%	3 3.0%
	Neuroendocrine	0 0.0%	3 4.2%	0 0.0%	0 0.0%	0 0.0%	3 3.0%
	Renal	1 14.3%	2 2.8%	0 0.0%	0 0.0%	0 0.0%	3 3.0%
	Thyroid	0 0.0%	3 4.2%	0 0.0%	0 0.0%	0 0.0%	3 3.0%
	Urethral	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
	Gastroesophageal	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
	Cervix	0 0.0%	2 2.8%	0 0.0%	0 0.0%	0 0.0%	2 2.0%
	Gastric	0 0.0%	2 2.8%	0 0.0%	0 0.0%	0 0.0%	2 2.0%
	Non-small cell lung	0 0.0%	2 2.8%	0 0.0%	0 0.0%	0 0.0%	2 2.0%
	Pancreatic	0 0.0%	2 2.8%	0 0.0%	0 0.0%	0 0.0%	2 2.0%
	Pelvic	0 0.0%	2 2.8%	0 0.0%	0 0.0%	0 0.0%	2 2.0%
	Peritoneal	0 0.0%	2 2.8%	0 0.0%	0 0.0%	0 0.0%	2 2.0%
	Hepatocellular carcinoma	0 0.0%	1 1.4%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
	Merkel cell	0 0.0%	1 1.4%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
	Penile	0 0.0%	1 1.4%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
	Retroperitoneal teratoma	0 0.0%	1 1.4%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
	Papilla of vater	0 0.0%	1 1.4%	0 0.0%	0 0.0%	0 0.0%	1 1.0%
		[1] Measure Description: The type of primary tumor diagnosed in the patient, as identified and reported by the investigator. This measure is derived from clinical assessments, imaging studies, histopathological evaluations, and/or medical records.

Outcome Measures

1.Primary Outcome


Title	Clinical Benefit Rate (CBR) of Nivolumab With or Without Ipilimumab
Description	CBR is defined as the percentage of participants who show clinical ben...
Description	CBR is defined as the percentage of participants who show clinical benefit, defined as obtaining a complete response (CR; disappearance of all target and non-target lesions), partial response (PR; ≥ 30% decrease in the sum of the longest diameter of target lesions), or stable disease (SD) for ≥ 6 months, as determined by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.
Time Frame	Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description:	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description:	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
Overall Number of Participants Analyzed	7	72	1	5	15
Measure Type: Count of Participants Unit of Measure: Participants
	1 14.3%	18 25.0%	1 100.0%	1 20.0%	3 20.0%

2.Primary Outcome


Title	Percentage of Participants Whose Tumors Convert From CD8 Low (<15% Tumoral CD8) to CD8 High (>=15%).
Description	Percentage of participants in the nivolumab plus ipilimumab ("CD8...
Description	Percentage of participants in the nivolumab plus ipilimumab ("CD8 low") arm whose tumors convert from CD8 low (<15%) to CD8 high (>=15%) as measured by the percentage of tumoral CD8 cells. Participants in the CD8 high arms are not evaluated for this outcome. On-treatment biopsies for the advanced metastatic cancer cohort were scheduled for as early as possible after the 2nd and 4th doses of ipilimumab (Day 2 - 10 of Cycle 2 and Cycle 6, respectively). On-treatment biopsies for the advanced prostate cancer cohort were scheduled for within 3 days (+/-) of the 2nd and 4th doses of nivolumab (Day 22 of Cycle 1 and Cycle 2, respectively).
Time Frame	From initiation of study intervention through the 2nd on-treatment tumor biopsy, up to 8 months

Outcome Measure Data

Analysis Population Description

Only CD8 low participants with an on-treatment biopsy are included in the analysis population for this outcome. Participants in the CD8 high arms and participants without an on-treatment biopsy are not evaluated for this outcome.


Arm/Group Title	"Cold" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description:	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description:	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
Overall Number of Participants Analyzed	39	3	8
Measure Type: Count of Participants Unit of Measure: Participants
	14 35.9%	1 33.3%	1 12.5%

3.Secondary Outcome


Title	Number of Participants With Treatment-related Adverse Events (TRAE)
Description	Investigators recorded adverse events (AEs) during each participant en...
Description	Investigators recorded adverse events (AEs) during each participant encounter. AE severity was assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, which grades AEs on a 1 to 5 scale: Grades 1 and 2 indicate mild to moderate events; Grade 3 denotes severe events; Grades 4 and 5 signify life-threatening or fatal outcomes. A TRAE is defined as any event that either occurs after the initiation of study intervention, having been absent at baseline, or, if present at baseline, appears to have worsened in severity or frequency, that is deemed 'Possibly', 'Probably', or 'Definitely' related to the intervention by the Investigator. All TRAEs were collected from the time the participant signed informed consent until 100 days after the last dose of study intervention. Prior to initiation of study intervention, only TRAEs that were related to a protocol mandated intervention, including those that occurred prior to being assigned to a study arm, were reported.
Time Frame	From signing informed consent (prior to Screening) through 100 days after last dose, up to 43 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description:	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description:	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
Overall Number of Participants Analyzed	7	72	1	5	15
Measure Type: Count of Participants Unit of Measure: Participants
Any Treatment-related adverse event (TRAE)	4 57.1%	58 80.6%	1 100.0%	4 80.0%	12 80.0%
Grade 3 or Grade 4 TRAE	0 0.0%	20 27.8%	0 0.0%	2 40.0%	6 40.0%
Grade 5 TRAE	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Serious TRAE	0 0.0%	10 13.9%	0 0.0%	1 20.0%	6 40.0%
TRAE leading to treatment discontinuation	0 0.0%	4 5.6%	0 0.0%	0 0.0%	5 33.3%

4.Secondary Outcome


Title	Objective Response Rate (ORR)
Description	Objective Response Rate (ORR) is defined as the percentage of particip...
Description	Objective Response Rate (ORR) is defined as the percentage of participants who attain a best overall response of complete response (CR; disappearance of all target and non-target lesions) or partial response (PR; >= 30% decrease in the sum of the longest diameter of target lesions), as determined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.
Time Frame	Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description:	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description:	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
Overall Number of Participants Analyzed	7	72	1	5	15
Measure Type: Count of Participants Unit of Measure: Participants
	1 14.3%	14 19.4%	0 0.0%	0 0.0%	1 6.7%

5.Secondary Outcome


Title	Progression-free Survival (PFS)
Description	PFS is defined as the time from initiation of study intervention to th...
Description	PFS is defined as the time from initiation of study intervention to the date of first documented radiographic progression of disease or date of death due to any cause, whichever occurred first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Initiation of study drug through death, radiographic progression or initiation of new anti-cancer therapy, whichever occurred first, up to 43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description:	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description:	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
Overall Number of Participants Analyzed	7	72	1	5	15
Median (95% Confidence Interval) Unit of Measure: months
	2.0 ^[1] (1.1 to NA)	2.3 (2.0 to 4.3)	NA ^[2] (NA to NA)	3.7 ^[1] (1.1 to NA)	5.7 (2.0 to 7.9)

[1]

Upper confidence limit is not estimable due to insufficient number of participants with events.

[2]

Median and confidence limits are not estimable due to insufficient number of participants with events.

6.Secondary Outcome


Title	Overall Survival (OS)
Description	OS is defined as the time from initiation of study intervention until ...
Description	OS is defined as the time from initiation of study intervention until death due to any cause. Participants not reported as having died at the time of analysis were censored at the most recent contact date they were known to be alive.
Time Frame	From initiation of study drug until death due to any cause, up to 43 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description:	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description:	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
Overall Number of Participants Analyzed	7	72	1	5	15
Median (95% Confidence Interval) Unit of Measure: months
	15.8 ^[1] (12.1 to NA)	13.9 (8.9 to 21.1)	NA ^[2] (NA to NA)	NA ^[2] (1.1 to NA)	NA ^[2] (4.9 to NA)

[1]

Upper confidence limit is not estimable due to insufficient number of participants with events.

[2]

Median and confidence limits are not estimable due to insufficient number of participants with events.

Adverse Events

Time Frame	From initiation of study drug until death due to any cause, up to 43 months. All adverse events (AEs), regardless of relationship to study drug, were collected from the time the participant signed informed consent until 100 days after the last dose of study intervention. Serious Adverse Events (SAEs) that occurred after the end of the AE reporting period (100-days post last dose) and that were considered to be reasonably related to the study drug by the investigator, were also collected.
Adverse Event Reporting Description	Investigators recorded AEs during each participant encounter. All AEs, regardless of relationship to study drug, were collected from the time the participant signed informed consent until 100 days after the last dose of study intervention. Prior to initiation of study intervention, only AEs that were related to a protocol mandated intervention (e.g. biopsy), including those that occurred prior to being assigned to a study arm, were collected.

Arm/Group Title	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
Arm/Group Description	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with ≥ 15% CD8 cells i...	Participants with < 15% CD8 cells i...	Participants with < 15% CD8 cells i...
Arm/Group Description	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab and Combination for Metastatic Cancer: For nivolumab and ipilimumab combination therapy, nivolumab will be administered at 360 mg IV Q3W, and ipilimumab will be administered at 1 mg/kg IV Q3W for the first 2 doses and then Q6W for the 3rd and 4th doses, followed by single-agent nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with ≥ 15% CD8 cells in their tumor biopsies (ie, CD8 high tumors) will be treated with single-agent nivolumab. At PD, participants will be allowed to add ipilimumab. Nivolumab Monotherapy: Single-agent nivolumab will be administered at 360 mg IV Q3W. Participants who continue to show clinical benefit after the first disease assessment will receive nivolumab 480 mg IV Q4W until PD or intolerable toxicity.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (3 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort A will receive nivolumab 1 mg/kg Q3W and ipilimumab 3 mg/kg every 6 weeks (Q6W) for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If the safety profile of Prostate Cohort B is deemed unacceptable, an additional 10 participants will be enrolled in Prostate Cohort A.	Participants with < 15% CD8 cells in their tumor biopsies (ie, CD8 low tumors) will be treated with nivolumab in combination with ipilimumab. Nivolumab and Ipilimumab (5 mg/kg) Combination for Prostate Cancer: For nivolumab and ipilimumab combination therapy, CD8 low arm, approximately 10 participants will be randomly allocated into 1 of 2 cohorts, using different doses of ipilimumab administered in 6-week cycles. Participants assigned to Prostate Cohort B will receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity. If Prostate Cohort B is determined to have a tolerable safety profile, an additional 10 participants will be enrolled to receive nivolumab 1 mg/kg Q3W and ipilimumab 5 mg/kg Q6W for 2 cycles, then nivolumab maintenance 480 mg Q4W until PD or intolerable toxicity.
All-Cause Mortality
	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/7 (57.14%)	39/72 (54.17%)	0/1 (0.00%)	2/5 (40.00%)	6/15 (40.00%)
Serious Adverse Events Serious Adverse Events
	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	2/7 (28.57%)	30/72 (41.67%)	0/1 (0.00%)	2/5 (40.00%)	8/15 (53.33%)
Cardiac disorders
Cardio-respiratory arrest ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Myocardial infarction ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Acute Myocardial Infarction ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Endocrine disorders
Hypophysitis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Thyroiditis ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Adrenocortical Insufficiency Acute ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Immune-Mediated Adrenal Insufficiency ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Eye disorders
Retinal vascular disorder ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Vision blurred ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Gastrointestinal disorders
Anal incontinence ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Colitis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Constipation ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Gastritis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Oesophagitis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Vomiting ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Diarrhoea ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Immune-Mediated Enterocolitis ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	3/15 (20.00%)
General disorders
Fatigue ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Influenza like illness ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Pyrexia ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Hepatobiliary disorders
Cholecystitis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Hypertransaminasaemia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Immune-Mediated Hepatitis ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Immune system disorders
Hypersensitivity ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Infections and infestations
Peritonitis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Pneumonia ^† 1	0/7 (0.00%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Pneumonia aspiration ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Sepsis ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Urinary tract infection ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Covid-19 Pneumonia ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Injury, poisoning and procedural complications
Joint injury ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Amylase increased ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Lipase increased ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Aspartate Aminotransferase Increased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Blood Bilirubin Increased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Hypoglycaemia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Hypokalaemia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Hyponatraemia ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Muscular weakness ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Myositis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Osteoarthritis ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Rhabdomyolysis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Nervous system disorders
Ataxia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Syncope ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Transient ischaemic attack ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Guillain-Barre Syndrome ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Psychiatric disorders
Confusional state ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Renal and urinary disorders
Urinary incontinence ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Urinary Retention ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Haemoptysis ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Hypoxia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Skin and subcutaneous tissue disorders
Medical Device Site Cellulitis ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Vascular disorders
Hypotension ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
1 Term from vocabulary, MedDRA 25.0 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	"Hot" Tumors for Advanced Metastatic Cancer	"Cold" Tumors for Advanced Metastatic Cancer	"Hot" Tumors for Advanced Prostate Cancer	"Cold" Tumors for Advanced Prostate Cancer Cohort A	"Cold" Tumors for Advanced Prostate Cancer Cohort B
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	7/7 (100.00%)	71/72 (98.61%)	1/1 (100.00%)	5/5 (100.00%)	15/15 (100.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	1/7 (14.29%)	14/72 (19.44%)	0/1 (0.00%)	2/5 (40.00%)	2/15 (13.33%)
Thrombocytopenia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Cardiac disorders
Sinus Node Dysfunction ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Tachycardia ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Endocrine disorders
Adrenal Insufficiency ^† 1	0/7 (0.00%)	3/72 (4.17%)	0/1 (0.00%)	1/5 (20.00%)	2/15 (13.33%)
Hyperthyroidism ^† 1	1/7 (14.29%)	3/72 (4.17%)	0/1 (0.00%)	1/5 (20.00%)	2/15 (13.33%)
Hypophysitis ^† 1	1/7 (14.29%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Hypothyroidism ^† 1	2/7 (28.57%)	8/72 (11.11%)	0/1 (0.00%)	0/5 (0.00%)	3/15 (20.00%)
Thyroiditis ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Eye disorders
Eye pain ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Photophobia ^† 1	1/7 (14.29%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Vision Blurred ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Gastrointestinal disorders
Abdominal Pain ^† 1	1/7 (14.29%)	12/72 (16.67%)	0/1 (0.00%)	1/5 (20.00%)	2/15 (13.33%)
Abdominal pain upper ^† 1	1/7 (14.29%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Constipation ^† 1	1/7 (14.29%)	13/72 (18.06%)	0/1 (0.00%)	1/5 (20.00%)	4/15 (26.67%)
Diarrhoea ^† 1	0/7 (0.00%)	21/72 (29.17%)	0/1 (0.00%)	1/5 (20.00%)	3/15 (20.00%)
Dry Mouth ^† 1	0/7 (0.00%)	3/72 (4.17%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Dysphagia ^† 1	1/7 (14.29%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	2/15 (13.33%)
Gastrooesophageal Reflux Disease ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Nausea ^† 1	0/7 (0.00%)	18/72 (25.00%)	0/1 (0.00%)	1/5 (20.00%)	5/15 (33.33%)
Retching ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Stomatitis ^† 1	1/7 (14.29%)	6/72 (8.33%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Toothache ^† 1	0/7 (0.00%)	2/72 (2.78%)	1/1 (100.00%)	0/5 (0.00%)	1/15 (6.67%)
Vomiting ^† 1	2/7 (28.57%)	13/72 (18.06%)	0/1 (0.00%)	1/5 (20.00%)	4/15 (26.67%)
General disorders
Asthenia ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Chills ^† 1	0/7 (0.00%)	6/72 (8.33%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Facial pain ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Fatigue ^† 1	1/7 (14.29%)	36/72 (50.00%)	1/1 (100.00%)	3/5 (60.00%)	4/15 (26.67%)
Influenza like illness ^† 1	0/7 (0.00%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Oedema peripheral ^† 1	0/7 (0.00%)	4/72 (5.56%)	1/1 (100.00%)	1/5 (20.00%)	0/15 (0.00%)
Pyrexia ^† 1	1/7 (14.29%)	7/72 (9.72%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Hepatobiliary disorders
Hyperbilirubinaemia ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Infections and infestations
Bacteraemia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Body tinea ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Campylobacter Colitis ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Coronavirus infection ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Covid-19 ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Hordeolum ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Oral Candidiasis ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Otitis Externa ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Penile Infection ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Pneumonia ^† 1	0/7 (0.00%)	3/72 (4.17%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Skin Infection ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Upper respiratory tract infection ^† 1	0/7 (0.00%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Urinary Tract Infection ^† 1	0/7 (0.00%)	3/72 (4.17%)	0/1 (0.00%)	1/5 (20.00%)	1/15 (6.67%)
Injury, poisoning and procedural complications
Skin Laceration ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Investigations
Alanine Aminotransferase Increased ^† 1	0/7 (0.00%)	6/72 (8.33%)	0/1 (0.00%)	1/5 (20.00%)	3/15 (20.00%)
Amylase Increased ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Aspartate Aminotransferase Increased ^† 1	0/7 (0.00%)	9/72 (12.50%)	0/1 (0.00%)	1/5 (20.00%)	3/15 (20.00%)
Blood Creatinine Increased ^† 1	1/7 (14.29%)	10/72 (13.89%)	0/1 (0.00%)	1/5 (20.00%)	1/15 (6.67%)
Blood bilirubin increased ^† 1	0/7 (0.00%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Blood Lactate Dehydrogenase Increased ^† 1	1/7 (14.29%)	1/72 (1.39%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Blood Thyroid Stimulating Hormone Increased ^† 1	0/7 (0.00%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Lipase increased ^† 1	0/7 (0.00%)	11/72 (15.28%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Low Density Lipoprotein Increased ^† 1	0/7 (0.00%)	0/72 (0.00%)	1/1 (100.00%)	0/5 (0.00%)	0/15 (0.00%)
Lymphocyte count decreased ^† 1	0/7 (0.00%)	5/72 (6.94%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Pancreatic Enzymes Increased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	2/15 (13.33%)
Sars-Cov-2 Test Positive ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Thyroid Function Test Abnormal ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Thyroxine Decreased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Transaminases increased ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Tri-Iodothyronine Decreased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Troponin I Increased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Troponin Increased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Weight Decreased ^† 1	1/7 (14.29%)	5/72 (6.94%)	0/1 (0.00%)	0/5 (0.00%)	4/15 (26.67%)
Weight Increased ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
White Blood Cell Count Decreased ^† 1	1/7 (14.29%)	1/72 (1.39%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Metabolism and nutrition disorders
Decreased Appetite ^† 1	2/7 (28.57%)	13/72 (18.06%)	0/1 (0.00%)	2/5 (40.00%)	2/15 (13.33%)
Dehydration ^† 1	0/7 (0.00%)	7/72 (9.72%)	0/1 (0.00%)	1/5 (20.00%)	1/15 (6.67%)
Hyperglycaemia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	2/5 (40.00%)	0/15 (0.00%)
Hyperkalaemia ^† 1	1/7 (14.29%)	1/72 (1.39%)	0/1 (0.00%)	1/5 (20.00%)	2/15 (13.33%)
Hypernatraemia ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Hypoalbuminaemia ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Hypocalcaemia ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	1/5 (20.00%)	2/15 (13.33%)
Hypokalaemia ^† 1	1/7 (14.29%)	4/72 (5.56%)	0/1 (0.00%)	2/5 (40.00%)	3/15 (20.00%)
Hypomagnesaemia ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Hyponatraemia ^† 1	0/7 (0.00%)	8/72 (11.11%)	0/1 (0.00%)	2/5 (40.00%)	2/15 (13.33%)
Hypophosphataemia ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	2/15 (13.33%)
Malnutrition ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	2/15 (13.33%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	1/7 (14.29%)	10/72 (13.89%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Back pain ^† 1	0/7 (0.00%)	11/72 (15.28%)	0/1 (0.00%)	0/5 (0.00%)	3/15 (20.00%)
Flank Pain ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	1/5 (20.00%)	1/15 (6.67%)
Muscle spasms ^† 1	0/7 (0.00%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Muscular weakness ^† 1	0/7 (0.00%)	6/72 (8.33%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Musculoskeletal Chest Pain ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Myalgia ^† 1	0/7 (0.00%)	12/72 (16.67%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Neck pain ^† 1	2/7 (28.57%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Osteoarthritis ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Pain In Extremity ^† 1	1/7 (14.29%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	2/15 (13.33%)
Polymyalgia Rheumatica ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer Pain ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Extradural Neoplasm ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Tumour pain ^† 1	1/7 (14.29%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Nervous system disorders
Bell's Palsy ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Dizziness ^† 1	0/7 (0.00%)	6/72 (8.33%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Haemorrhage Intracranial ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Headache ^† 1	1/7 (14.29%)	11/72 (15.28%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Trigeminal neuralgia ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Spinal Cord Compression ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Psychiatric disorders
Anxiety ^† 1	0/7 (0.00%)	3/72 (4.17%)	0/1 (0.00%)	1/5 (20.00%)	2/15 (13.33%)
Insomnia ^† 1	0/7 (0.00%)	7/72 (9.72%)	0/1 (0.00%)	0/5 (0.00%)	2/15 (13.33%)
Renal and urinary disorders
Acute Kidney Injury ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Chronic Kidney Disease ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Cystitis Noninfective ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Hydronephrosis ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Nephrolithiasis ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Renal Failure ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Urinary Tract Obstruction ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Cough ^† 1	1/7 (14.29%)	13/72 (18.06%)	0/1 (0.00%)	0/5 (0.00%)	3/15 (20.00%)
Dysphonia ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Dyspnoea ^† 1	0/7 (0.00%)	18/72 (25.00%)	0/1 (0.00%)	1/5 (20.00%)	3/15 (20.00%)
Hypoxia ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Oropharyngeal pain ^† 1	0/7 (0.00%)	4/72 (5.56%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Pleural Effusion ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Productive cough ^† 1	1/7 (14.29%)	3/72 (4.17%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Respiratory Failure ^† 1	0/7 (0.00%)	1/72 (1.39%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Upper-Airway Cough Syndrome ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Wheezing ^† 1	0/7 (0.00%)	2/72 (2.78%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Skin and subcutaneous tissue disorders
Dermatitis Bullous ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Pain of skin ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Pruritus ^† 1	1/7 (14.29%)	12/72 (16.67%)	0/1 (0.00%)	0/5 (0.00%)	1/15 (6.67%)
Rash ^† 1	1/7 (14.29%)	15/72 (20.83%)	1/1 (100.00%)	2/5 (40.00%)	4/15 (26.67%)
Rash maculo-papular ^† 1	0/7 (0.00%)	6/72 (8.33%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Rash pruritic ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Surgical and medical procedures
Abscess drainage ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Vascular disorders
Embolism Venous ^† 1	0/7 (0.00%)	0/72 (0.00%)	0/1 (0.00%)	1/5 (20.00%)	0/15 (0.00%)
Hypertension ^† 1	1/7 (14.29%)	7/72 (9.72%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Hypotension ^† 1	0/7 (0.00%)	3/72 (4.17%)	0/1 (0.00%)	1/5 (20.00%)	1/15 (6.67%)
Jugular vein thrombosis ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
Lymphoedema ^† 1	1/7 (14.29%)	0/72 (0.00%)	0/1 (0.00%)	0/5 (0.00%)	0/15 (0.00%)
1 Term from vocabulary, MedDRA 25.0 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Trial Site and/or Co-Principal Investigators may publish or present Study Data and other results of the Study from the Trial Site individually upon the first to occur of: (i) twelve (12) months after conclusion, abandonment, or termination of the Study at all Affiliated Research Institutions, or (ii) after Parker Institute for Cancer Immunotherapy (PICI) confirms in writing there will not be a multi-site Study publication.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Ute Dugan
Organization:	Parker Institute for Cancer Immunotherapy
Phone:	203-379-6757
EMail:	udugan@parkerici.org

Publications:

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR, Albright A, Cheng JD, Kang SP, Shankaran V, Piha-Paul SA, Yearley J, Seiwert TY, Ribas A, McClanahan TK. IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017 Aug 1;127(8):2930-2940. doi: 10.1172/JCI91190. Epub 2017 Jun 26.

Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

Chen PL, Roh W, Reuben A, Cooper ZA, Spencer CN, Prieto PA, Miller JP, Bassett RL, Gopalakrishnan V, Wani K, De Macedo MP, Austin-Breneman JL, Jiang H, Chang Q, Reddy SM, Chen WS, Tetzlaff MT, Broaddus RJ, Davies MA, Gershenwald JE, Haydu L, Lazar AJ, Patel SP, Hwu P, Hwu WJ, Diab A, Glitza IC, Woodman SE, Vence LM, Wistuba II, Amaria RN, Kwong LN, Prieto V, Davis RE, Ma W, Overwijk WW, Sharpe AH, Hu J, Futreal PA, Blando J, Sharma P, Allison JP, Chin L, Wargo JA. Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade. Cancer Discov. 2016 Aug;6(8):827-37. doi: 10.1158/2159-8290.CD-15-1545. Epub 2016 Jun 14.

Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

Feldmeyer L, Hudgens CW, Ray-Lyons G, Nagarajan P, Aung PP, Curry JL, Torres-Cabala CA, Mino B, Rodriguez-Canales J, Reuben A, Chen PL, Ko JS, Billings SD, Bassett RL, Wistuba II, Cooper ZA, Prieto VG, Wargo JA, Tetzlaff MT. Density, Distribution, and Composition of Immune Infiltrates Correlate with Survival in Merkel Cell Carcinoma. Clin Cancer Res. 2016 Nov 15;22(22):5553-5563. doi: 10.1158/1078-0432.CCR-16-0392. Epub 2016 May 10.

Gao J, Ward JF, Pettaway CA, Shi LZ, Subudhi SK, Vence LM, Zhao H, Chen J, Chen H, Efstathiou E, Troncoso P, Allison JP, Logothetis CJ, Wistuba II, Sepulveda MA, Sun J, Wargo J, Blando J, Sharma P. VISTA is an inhibitory immune checkpoint that is increased after ipilimumab therapy in patients with prostate cancer. Nat Med. 2017 May;23(5):551-555. doi: 10.1038/nm.4308. Epub 2017 Mar 27.

Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.

Haanen JBAG. Converting Cold into Hot Tumors by Combining Immunotherapies. Cell. 2017 Sep 7;170(6):1055-1056. doi: 10.1016/j.cell.2017.08.031.

Hegde PS, Karanikas V, Evers S. The Where, the When, and the How of Immune Monitoring for Cancer Immunotherapies in the Era of Checkpoint Inhibition. Clin Cancer Res. 2016 Apr 15;22(8):1865-74. doi: 10.1158/1078-0432.CCR-15-1507.

Herbst RS, Baas P, Kim DW, Felip E, Perez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Castro G Jr, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016 Apr 9;387(10027):1540-1550. doi: 10.1016/S0140-6736(15)01281-7. Epub 2015 Dec 19.

Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5. Erratum In: N Engl J Med. 2010 Sep 23;363(13):1290.

Johnson DB, Estrada MV, Salgado R, Sanchez V, Doxie DB, Opalenik SR, Vilgelm AE, Feld E, Johnson AS, Greenplate AR, Sanders ME, Lovly CM, Frederick DT, Kelley MC, Richmond A, Irish JM, Shyr Y, Sullivan RJ, Puzanov I, Sosman JA, Balko JM. Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1/PD-L1 therapy. Nat Commun. 2016 Jan 29;7:10582. doi: 10.1038/ncomms10582.

Kvistborg P, Philips D, Kelderman S, Hageman L, Ottensmeier C, Joseph-Pietras D, Welters MJ, van der Burg S, Kapiteijn E, Michielin O, Romano E, Linnemann C, Speiser D, Blank C, Haanen JB, Schumacher TN. Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response. Sci Transl Med. 2014 Sep 17;6(254):254ra128. doi: 10.1126/scitranslmed.3008918.

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, Ferrucci PF, Hill A, Wagstaff J, Carlino MS, Haanen JB, Maio M, Marquez-Rodas I, McArthur GA, Ascierto PA, Long GV, Callahan MK, Postow MA, Grossmann K, Sznol M, Dreno B, Bastholt L, Yang A, Rollin LM, Horak C, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34. doi: 10.1056/NEJMoa1504030. Epub 2015 May 31. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185.

Maby P, Galon J, Latouche JB. Frameshift mutations, neoantigens and tumor-specific CD8(+) T cells in microsatellite unstable colorectal cancers. Oncoimmunology. 2015 Nov 24;5(5):e1115943. doi: 10.1080/2162402X.2015.1115943. eCollection 2016 May.

Maio M, Grob JJ, Aamdal S, Bondarenko I, Robert C, Thomas L, Garbe C, Chiarion-Sileni V, Testori A, Chen TT, Tschaika M, Wolchok JD. Five-year survival rates for treatment-naive patients with advanced melanoma who received ipilimumab plus dacarbazine in a phase III trial. J Clin Oncol. 2015 Apr 1;33(10):1191-6. doi: 10.1200/JCO.2014.56.6018. Epub 2015 Feb 23.

Momtaz P, Park V, Panageas KS, Postow MA, Callahan M, Wolchok JD, Chapman PB. Safety of Infusing Ipilimumab Over 30 Minutes. J Clin Oncol. 2015 Oct 20;33(30):3454-8. doi: 10.1200/JCO.2015.61.0030. Epub 2015 Jun 29.

Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu LA, Waxman IM, Sharma P; CheckMate 025 Investigators. Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma. N Engl J Med. 2015 Nov 5;373(19):1803-13. doi: 10.1056/NEJMoa1510665. Epub 2015 Sep 25.

Motzer RJ, Tannir NM, McDermott DF, Aren Frontera O, Melichar B, Choueiri TK, Plimack ER, Barthelemy P, Porta C, George S, Powles T, Donskov F, Neiman V, Kollmannsberger CK, Salman P, Gurney H, Hawkins R, Ravaud A, Grimm MO, Bracarda S, Barrios CH, Tomita Y, Castellano D, Rini BI, Chen AC, Mekan S, McHenry MB, Wind-Rotolo M, Doan J, Sharma P, Hammers HJ, Escudier B; CheckMate 214 Investigators. Nivolumab plus Ipilimumab versus Sunitinib in Advanced Renal-Cell Carcinoma. N Engl J Med. 2018 Apr 5;378(14):1277-1290. doi: 10.1056/NEJMoa1712126. Epub 2018 Mar 21.

Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015 Apr 3;348(6230):124-8. doi: 10.1126/science.aaa1348. Epub 2015 Mar 12.

Robert C, Schachter J, Long GV, Arance A, Grob JJ, Mortier L, Daud A, Carlino MS, McNeil C, Lotem M, Larkin J, Lorigan P, Neyns B, Blank CU, Hamid O, Mateus C, Shapira-Frommer R, Kosh M, Zhou H, Ibrahim N, Ebbinghaus S, Ribas A; KEYNOTE-006 investigators. Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015 Jun 25;372(26):2521-32. doi: 10.1056/NEJMoa1503093. Epub 2015 Apr 19.

Roy S, Trinchieri G. Microbiota: a key orchestrator of cancer therapy. Nat Rev Cancer. 2017 May;17(5):271-285. doi: 10.1038/nrc.2017.13. Epub 2017 Mar 17.

Schadendorf D, Hodi FS, Robert C, Weber JS, Margolin K, Hamid O, Patt D, Chen TT, Berman DM, Wolchok JD. Pooled Analysis of Long-Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2015 Jun 10;33(17):1889-94. doi: 10.1200/JCO.2014.56.2736. Epub 2015 Feb 9.

Thall PF, Simon RM, Estey EH. Bayesian sequential monitoring designs for single-arm clinical trials with multiple outcomes. Stat Med. 1995 Feb 28;14(4):357-79. doi: 10.1002/sim.4780140404.

Thompson ED, Zahurak M, Murphy A, Cornish T, Cuka N, Abdelfatah E, Yang S, Duncan M, Ahuja N, Taube JM, Anders RA, Kelly RJ. Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma. Gut. 2017 May;66(5):794-801. doi: 10.1136/gutjnl-2015-310839. Epub 2016 Jan 22.

Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, Chmielowski B, Spasic M, Henry G, Ciobanu V, West AN, Carmona M, Kivork C, Seja E, Cherry G, Gutierrez AJ, Grogan TR, Mateus C, Tomasic G, Glaspy JA, Emerson RO, Robins H, Pierce RH, Elashoff DA, Robert C, Ribas A. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014 Nov 27;515(7528):568-71. doi: 10.1038/nature13954.

Weber JS, D'Angelo SP, Minor D, Hodi FS, Gutzmer R, Neyns B, Hoeller C, Khushalani NI, Miller WH Jr, Lao CD, Linette GP, Thomas L, Lorigan P, Grossmann KF, Hassel JC, Maio M, Sznol M, Ascierto PA, Mohr P, Chmielowski B, Bryce A, Svane IM, Grob JJ, Krackhardt AM, Horak C, Lambert A, Yang AS, Larkin J. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2015 Apr;16(4):375-84. doi: 10.1016/S1470-2045(15)70076-8. Epub 2015 Mar 18.

Wolchok JD, Hoos A, O'Day S, Weber JS, Hamid O, Lebbe C, Maio M, Binder M, Bohnsack O, Nichol G, Humphrey R, Hodi FS. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009 Dec 1;15(23):7412-20. doi: 10.1158/1078-0432.CCR-09-1624. Epub 2009 Nov 24.

Wolchok JD, Chiarion-Sileni V, Gonzalez R, Rutkowski P, Grob JJ, Cowey CL, Lao CD, Wagstaff J, Schadendorf D, Ferrucci PF, Smylie M, Dummer R, Hill A, Hogg D, Haanen J, Carlino MS, Bechter O, Maio M, Marquez-Rodas I, Guidoboni M, McArthur G, Lebbe C, Ascierto PA, Long GV, Cebon J, Sosman J, Postow MA, Callahan MK, Walker D, Rollin L, Bhore R, Hodi FS, Larkin J. Overall Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma. N Engl J Med. 2017 Oct 5;377(14):1345-1356. doi: 10.1056/NEJMoa1709684. Epub 2017 Sep 11. Erratum In: N Engl J Med. 2018 Nov 29;379(22):2185.

Layout table for additonal information

Responsible Party:	Parker Institute for Cancer Immunotherapy
ClinicalTrials.gov Identifier:	NCT03651271
Other Study ID Numbers:	PICI0025
First Submitted:	August 27, 2018
First Posted:	August 29, 2018
Results First Submitted:	December 20, 2023
Results First Posted:	January 17, 2024
Last Update Posted:	February 7, 2024

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