Safety and Efficacy of APX005M With Gemcitabine and Nab-Paclitaxel With or Without Nivolumab in Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma

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ClinicalTrials.gov Identifier: NCT03214250

Recruitment Status : Completed

First Posted : July 11, 2017

Results First Posted : August 11, 2022

Last Update Posted : December 23, 2022

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Sponsor:

Collaborators:

Bristol-Myers Squibb

Apexigen America, Inc.

Cancer Research Institute, New York City

Information provided by (Responsible Party):

Parker Institute for Cancer Immunotherapy

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Metastatic Pancreatic Adenocarcinoma
Interventions	Drug: APX005M Drug: Nivolumab Drug: Nab-Paclitaxel Drug: Gemcitabine
Enrollment	129

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Phase 1b: Gem/NP/APX005M (0.1 mg/kg)	Phase 1b: Gem/NP/APX005M (0.3 mg/kg)	Phase 1b: Gem/NP/Nivolumab/APX005M (0.1 mg/kg)	Phase 1b: Gem/NP/Nivolumab/APX005M (0.3 mg/kg)	Phase 2: Gem/NP/Nivolumab	Phase 2: Gem/NP/APX005M (0.3 mg/kg)	Phase 2: Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description	Gemcitabine+Nab-Paclitaxel+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Period Title: Overall Study
Started	7	7	8	8	37	31	31
Completed ^[1]	0	0	0	0	0	0	0
Not Completed	7	7	8	8	37	31	31
Reason Not Completed
Death	5	5	7	4	23	23	24
Lost to Follow-up	0	0	0	1	1	2	0
Other	0	0	0	0	1	1	2
Remains on Study	2	2	0	1	7	5	3
Withdrawal by Subject	0	0	1	2	5	0	2
[1] Per the protocol, "completed" status is defined as completing 5 years of survival follow-up from the time a patient has discontinued treatment.

Baseline Characteristics

Arm/Group Title		Phase 1b: Gem/NP/APX005M (0.1 mg/kg)	Phase 1b: Gem/NP/APX005M (0.3 mg/kg)	Phase 1b: Gem/NP/Nivolumab/APX005M (0.1 mg/kg)	Phase 1b: Gem/NP/Nivolumab/APX005M (0.3 mg/kg)	Phase 2: Gem/NP/Nivolumab	Phase 2: Gem/NP/APX005M (0.3 mg/kg)	Phase 2: Gem/NP/Nivolumab/APX005M (0.3 mg/kg)	Total
Arm/Group Description		Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Total of all reporting groups
Arm/Group Description		Gemcitabine+Nab-Paclitaxel+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Total of all reporting groups
Overall Number of Baseline Participants		7	7	8	8	37	31	31	129
Baseline Analysis Population Description		...
Baseline Analysis Population Description		The Phase 1b Safety Population is defined as all patients who were enrolled in Phase 1b and who received at least 1 dose of any study drug. The Phase 2 Efficacy Population is defined as all patients who were randomized in Phase 2 and who received at least 1 dose of any study drug.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	2 28.6%	4 57.1%	1 12.5%	6 75.0%	21 56.8%	18 58.1%	18 58.1%	70 54.3%
	>=65 years	5 71.4%	3 42.9%	7 87.5%	2 25.0%	16 43.2%	13 41.9%	13 41.9%	59 45.7%
Age, Continuous Median (Full Range) Unit of measure: Years
	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
		66.0 (52 to 73)	64.0 (54 to 76)	70.0 (61 to 79)	61.0 (39 to 71)	64.0 (47 to 75)	60.0 (35 to 78)	62 (34 to 78)	63.0 (34 to 79)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
	Female	5 71.4%	2 28.6%	3 37.5%	4 50.0%	16 43.2%	11 35.5%	13 41.9%	54 41.9%
	Male	2 28.6%	5 71.4%	5 62.5%	4 50.0%	21 56.8%	20 64.5%	18 58.1%	75 58.1%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%	1 2.7%	1 3.2%	2 6.5%	4 3.1%
	Not Hispanic or Latino	7 100.0%	7 100.0%	8 100.0%	8 100.0%	36 97.3%	30 96.8%	29 93.5%	125 96.9%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized Measure Type: Count of Participants Unit of measure: Participants
Race	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
	Asian	0 0.0%	0 0.0%	1 12.5%	1 12.5%	3 8.1%	4 12.9%	1 3.2%	10 7.8%
	Black or African American	0 0.0%	1 14.3%	0 0.0%	1 12.5%	0 0.0%	2 6.5%	1 3.2%	5 3.9%
	White	7 100.0%	6 85.7%	7 87.5%	6 75.0%	32 86.5%	24 77.4%	26 83.9%	108 83.7%
	Other	0 0.0%	0 0.0%	0 0.0%	0 0.0%	2 5.4%	1 3.2%	3 9.7%	6 4.7%
ECOG Performance Score ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
	ECOG Score = 0	3 42.9%	1 14.3%	5 62.5%	4 50.0%	17 45.9%	19 61.3%	14 45.2%	63 48.8%
	ECOG Score = 1	4 57.1%	6 85.7%	3 37.5%	4 50.0%	20 54.1%	12 38.7%	17 54.8%	66 51.2%
		[1] Measure Description: The Eastern Cooperative Oncology Group (ECOG) Scale of Performance Status is one such measurement. It describes a patient's level of functioning in terms of their ability to care for themself, daily activity, and physical ability (walking, working, etc.). The ECOG Performance Status ranges from 0 (fully active, able to carry on all pre-disease performance without restriction) to 5 (dead).
Cancer Location Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
	Pancreas Body	2 28.6%	4 57.1%	4 50.0%	1 12.5%	13 35.1%	6 19.4%	9 29.0%	39 30.2%
	Pancreas Head	4 57.1%	3 42.9%	2 25.0%	6 75.0%	15 40.5%	15 48.4%	15 48.4%	60 46.5%
	Pancreas Tail	1 14.3%	0 0.0%	2 25.0%	1 12.5%	9 24.3%	10 32.3%	7 22.6%	30 23.3%
Prior Treatment Measure Type: Count of Participants Unit of measure: Participants	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
Prior Chemotherapy	Yes	3 42.9%	2 28.6%	1 12.5%	3 37.5%	9 24.3%	5 16.1%	4 12.9%	27 20.9%
Prior Chemotherapy	No	4 57.1%	5 71.4%	7 87.5%	5 62.5%	28 75.7%	26 83.9%	27 87.1%	102 79.1%
Prior Cancer Surgery	Yes	3 42.9%	3 42.9%	1 12.5%	4 50.0%	11 29.7%	8 25.8%	5 16.1%	35 27.1%
Prior Cancer Surgery	No	4 57.1%	4 57.1%	7 87.5%	4 50.0%	26 70.3%	23 74.2%	26 83.9%	94 72.9%
Prior Radiation	Yes	1 14.3%	0 0.0%	1 12.5%	3 37.5%	7 18.9%	1 3.2%	2 6.5%	15 11.6%
Prior Radiation	No	6 85.7%	7 100.0%	7 87.5%	5 62.5%	30 81.1%	30 96.8%	29 93.5%	114 88.4%
Cancer Stage at Initial Diagnosis Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	7 participants	7 participants	8 participants	8 participants	37 participants	31 participants	31 participants	129 participants
	Stage 1	0 0.0%	1 14.3%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	4 12.9%	5 3.9%
	Stage 2	2 28.6%	3 42.9%	2 25.0%	4 50.0%	4 10.8%	4 12.9%	2 6.5%	21 16.3%
	Stage 3	1 14.3%	0 0.0%	0 0.0%	0 0.0%	3 8.1%	1 3.2%	1 3.2%	6 4.7%
	Stage 4	4 57.1%	3 42.9%	6 75.0%	4 50.0%	30 81.1%	26 83.9%	24 77.4%	97 75.2%

Outcome Measures

1.Primary Outcome


Title	Phase 1b Primary Safety Outcome
Description	Number and percentage of subjects with adverse events (AEs), serious a...
Description	Number and percentage of subjects with adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs)
Time Frame	Initiation of study drug (or informed consent for SAEs) through 100 days after the last dose of study drug or initiation of a new systemic anti-cancer therapy with a maximum exposure of 34.3 months.

Outcome Measure Data

Analysis Population Description

The DLT-Evaluable Population is defined as all Phase 1b patients who received at least 2 doses of NP, at least 2 doses of Gem, and 1 dose of APX005M during Cycle 1.


Arm/Group Title	Phase 1b: Gem/NP/APX005M (0.1 mg/kg)	Phase 1b: Gem/NP/APX005M (0.3 mg/kg)	Phase 1b: Gem/NP/Nivolumab/APX005M (0.1 mg/kg)	Phase 1b: Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	6	6	6	6
Measure Type: Count of Participants Unit of Measure: Participants
Adverse Events (AEs)	6 100.0%	6 100.0%	6 100.0%	6 100.0%
Serious Adverse Events (SAEs)	4 66.7%	4 66.7%	6 100.0%	1 16.7%
Dose-Limiting Toxicities (DLTs)	0 0.0%	1 16.7%	1 16.7%	0 0.0%

2.Primary Outcome


Title	1-year Overall Survival Rate
Description	The primary endpoint was the 1-year OS rate of each treatment arm, com...
Description	The primary endpoint was the 1-year OS rate of each treatment arm, compared to the historical rate of 35% for gemcitabine and nab-Paclitaxel. OS was defined as the time from treatment initiation until death from any cause. Patients who were not reported as having died at the time of analysis were censored at the most recent contact date. OS and the 1-year OS rate were estimated by the Kaplan-Meier method for each treatment arm. The 1-year OS rate and corresponding one-sided, 95% CI were calculated to determine whether the lower bound of the CI excluded the assumed historical value of 35%. P values were calculated using a one-sided, one-sample z-test of the Kaplan-Meier estimate of the 1-year OS rate (and its standard error) against the historical rate of 35%. This study was not powered for statistical comparison between arms.
Time Frame	1 year from initiation of study therapy

Outcome Measure Data

Analysis Population Description

The Efficacy Population is defined as (1) all patients who were randomized in Phase 2 and who received at least 1 dose of any study drug and (2) the 12 DLT-evaluable patients enrolled in Phase 1b at the recommended Phase 2 dose.


Arm/Group Title	Gem/NP/Nivolumab	Gem/NP/APX005M (0.3 mg/kg)	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	34	36	35
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: probability
	0.577 (0.384 to 0.729)	0.481 (0.309 to 0.634)	0.413 (0.244 to 0.575)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Gem/NP/Nivolumab
	Comments	Each treatment arm was analyzed independently and compared to a historical 1-year OS reference rate of 35%.
	Type of Statistical Test	Superiority
	Comments	One-sided

Statistical Test of Hypothesis	P-Value	0.006
	Comments	one-sided p-value
	Method	z-test
	Comments	One-sided, one-sample z-test of the Kaplan-Meier estimate of the 1-year OS rate (and its standard error) against the historical rate of 35%

Method of Estimation	Estimation Parameter	probability
	Estimated Value	0.577
	Confidence Interval	(1-Sided) 95% 0.417
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Gem/NP/APX005M (0.3 mg/kg)
	Comments	Each treatment arm was analyzed independently and compared to a historical 1-year OS reference rate of 35%.
	Type of Statistical Test	Superiority
	Comments	One-sided

Statistical Test of Hypothesis	P-Value	0.062
	Comments	one-sided p-value
	Method	z-test
	Comments	One-sided, one-sample z-test of the Kaplan-Meier estimate of the 1-year OS rate (and its standard error) against the historical rate of 35%

Method of Estimation	Estimation Parameter	probability
	Estimated Value	0.481
	Confidence Interval	(1-Sided) 95% 0.337
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
	Comments	Each treatment arm was analyzed independently and compared to a historical 1-year OS reference rate of 35%.
	Type of Statistical Test	Superiority
	Comments	One-sided

Statistical Test of Hypothesis	P-Value	0.233
	Comments	one-sided p-value
	Method	z-test
	Comments	One-sided, one-sample z-test of the Kaplan-Meier estimate of the 1-year OS rate (and its standard error) against the historical rate of 35%

Method of Estimation	Estimation Parameter	probability
	Estimated Value	0.413
	Confidence Interval	(1-Sided) 95% 0.270
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Objective Response Rate (ORR): DLT-Evaluable Population
Description	Phase 1b DLT-Evaluable Population. Overall Response Rate is defined as...
Description	Phase 1b DLT-Evaluable Population. Overall Response Rate is defined as the proportion of participants who had a best overall response of Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1. Overall Response (OR) = CR + PR.
Time Frame	Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 34.3 months.

Outcome Measure Data

Analysis Population Description

The DLT-Evaluable Population is defined as all Phase 1b patients who received at least 2 doses of NP, at least 2 doses of Gem, and 1 dose of APX005M during Cycle 1.


Arm/Group Title	Gem/NP/APX005M (0.1 mg/kg)	Gem/NP/APX005M (0.3 mg/kg)	Gem/NP/Nivolumab/APX005M (0.1 mg/kg)	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	6	6	6	6
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	66.7 (22.28 to 95.67)	33.3 (4.33 to 77.72)	66.7 (22.28 to 95.67)	66.7 (22.28 to 95.67)

4.Secondary Outcome


Title	Duration of Response (DOR): DLT-Evaluable Population
Description	DOR was the time from the first tumor assessment demonstrating respons...
Description	DOR was the time from the first tumor assessment demonstrating response until the date of radiographic disease progression. DOR and the CIs were estimated using the Kaplan-Meier method.
Time Frame	Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 34.3 months.

Outcome Measure Data

Analysis Population Description

Patients in the DLT-Evaluable Population (defined as all Phase 1b patients who received at least 2 doses of NP, at least 2 doses of Gem, and 1 dose of APX005M during Cycle 1) and who achieved a Partial Response or Complete Response.


Arm/Group Title	Gem/NP/APX005M (0.1 mg/kg)	Gem/NP/APX005M (0.3 mg/kg)	Gem/NP/Nivolumab/APX005M (0.1 mg/kg)	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	4	2	4	4
Median (95% Confidence Interval) Unit of Measure: months
	15.51 ^[1] (1.54 to NA)	7.03 ^[1] (6.01 to NA)	9.07 ^[1] (NA to NA)	10.35 ^[1] (5.32 to NA)

[1]

Some confidence limits are not estimable due to small sample sizes and censoring

5.Secondary Outcome


Title	Disease Control Rate (DCR)
Description	Phase 2 Secondary Efficacy Outcome. Disease Control Rate is defined as...
Description	Phase 2 Secondary Efficacy Outcome. Disease Control Rate is defined as the proportion of participants who had a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) as defined by RECIST v1.1.
Time Frame	Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Gem/NP/Nivolumab	Gem/NP/APX005M (0.3 mg/kg)	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	34	36	35
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	73.5 (55.64 to 87.12)	77.8 (60.85 to 89.88)	68.6 (50.71 to 83.15)

6.Secondary Outcome


Title	Progression-free Survival (PFS)
Description	PFS is defined as the time from treatment initiation until radiographi...
Description	PFS is defined as the time from treatment initiation until radiographic disease progression or death (whichever occurred first). PFS and the CIs were estimated using the Kaplan-Meier method.
Time Frame	Initiation of study drug through radiographic progression or death with a maximum exposure of 24.2 months.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Gem/NP/Nivolumab	Gem/NP/APX005M (0.3 mg/kg)	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	34	36	35
Median (95% Confidence Interval) Unit of Measure: months
	6.37 (5.19 to 8.80)	7.26 (5.36 to 9.23)	6.74 (4.17 to 9.79)

7.Secondary Outcome


Title	Objective Response Rate (ORR): Efficacy Population
Description	Phase 2 Secondary Efficacy Outcome. Overall Response Rate is defined a...
Description	Phase 2 Secondary Efficacy Outcome. Overall Response Rate is defined as the proportion of participants who had a best overall response of Complete Response (CR) or Partial Response (PR) as defined by RECIST v1.1. Overall Response (OR) = CR + PR.
Time Frame	Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Gem/NP/Nivolumab	Gem/NP/APX005M (0.3 mg/kg)	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	34	36	35
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: percentage of participants
	50 (32.43 to 67.57)	33.3 (18.56 to 50.97)	31.4 (16.85 to 49.29)

8.Secondary Outcome


Title	Duration of Response (DOR): Efficacy Population
Description	DOR was the time from the first tumor assessment demonstrating respons...
Description	DOR was the time from the first tumor assessment demonstrating response until the date of radiographic disease progression. DOR and the CIs were estimated using the Kaplan-Meier method.
Time Frame	Initiation of study drug through radiographic progression or initiation of new anti-cancer therapy with a maximum exposure of 24.2 months.

Outcome Measure Data

Analysis Population Description

Patients in the Efficacy Population (defined as all patients who were randomized in Phase 2 and who received at least 1 dose of any study drug and the 12 DLT-Evaluable patients enrolled in Phase 1b at the recommended Phase 2 dose) and who achieved a Partial Response or Complete Response.


Arm/Group Title	Gem/NP/Nivolumab	Gem/NP/APX005M (0.3 mg/kg)	Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivoluma...	Gemcitabine+Nab-Paclitaxel+APX005M ...	Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description:	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle	Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
Overall Number of Participants Analyzed	17	12	11
Median (95% Confidence Interval) Unit of Measure: months
	7.36 ^[1] (2.10 to NA)	5.55 (3.75 to 7.95)	7.88 ^[1] (1.91 to NA)

[1]

The upper confidence limit is not evaluable due to insufficient number of participants with events

Adverse Events

Time Frame	Adverse events were reported until 100 days after the last dose of study drug had been administered with a maximum exposure of 34.3 months.
Adverse Event Reporting Description	Safety analysis was conducted on all Phase 1b and Phase 2 patients who received at least one dose of any study drug. For safety analyses, patients were grouped according to the study treatment actually received ('as treated'). Specifically, two phase 2 patients were randomly allocated to Gem/NP/Nivolumab/APX005M but only received doses of Gem, NP, and Nivolumab (that is, APX005M was not received); these two patients were grouped as Gem/NP/APX005M for safety analyses.

Arm/Group Title	Gem/NP/Nivolumab		Gem/NP/APX005M (0.1 mg/kg)		Gem/NP/APX005M (0.3 mg/kg)		Gem/NP/Nivolumab/APX005M (0.1 mg/kg)		Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
Arm/Group Description	Gemcitabine+Nab-Paclitaxel+nivoluma...		Gemcitabine+Nab-Paclitaxel+APX005M ...		Gemcitabine+Nab-Paclitaxel+APX005M ...		Gemcitabine+Nab-Paclitaxel+nivoluma...		Gemcitabine+Nab-Paclitaxel+nivoluma...
Arm/Group Description	Gemcitabine+Nab-Paclitaxel+nivolumab Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle		Gemcitabine+Nab-Paclitaxel+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle		Gemcitabine+Nab-Paclitaxel+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle		Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.1 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle		Gemcitabine+Nab-Paclitaxel+nivolumab+APX005M (0.3 mg/kg) APX005M: Administer intravenously once every 28-day Cycle Nivolumab: Administer intravenously twice every 28-day cycle Nab-Paclitaxel: Administer intravenously on 3 times every 28-day cycle Gemcitabine: Administer intravenously 3 times every 28-day cycle
All-Cause Mortality
	Gem/NP/Nivolumab		Gem/NP/APX005M (0.1 mg/kg)		Gem/NP/APX005M (0.3 mg/kg)		Gem/NP/Nivolumab/APX005M (0.1 mg/kg)		Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	25/36 (69.44%)		5/7 (71.43%)		29/37 (78.38%)		8/8 (100.00%)		27/35 (77.14%)
Serious Adverse Events Serious Adverse Events
	Gem/NP/Nivolumab		Gem/NP/APX005M (0.1 mg/kg)		Gem/NP/APX005M (0.3 mg/kg)		Gem/NP/Nivolumab/APX005M (0.1 mg/kg)		Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/36 (50.00%)		4/7 (57.14%)		22/37 (59.46%)		6/8 (75.00%)		20/35 (57.14%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	2/35 (5.71%)	2
Febrile neutropenia ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	2/37 (5.41%)	2	0/8 (0.00%)	0	0/35 (0.00%)	0
Haemolytic uraemic syndrome ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	1/8 (12.50%)	1	0/35 (0.00%)	0
Thrombotic microangiopathy ^† 1	2/36 (5.56%)	2	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Cardiac disorders
Acute coronary syndrome ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Atrial fibrillation ^† 1	0/36 (0.00%)	0	1/7 (14.29%)	1	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Cardiac failure ^† 1	2/36 (5.56%)	2	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Myocarditis ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Tachycardia ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Eye disorders
Diplopia ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Ascites ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Diarrhoea ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Duodenal obstruction ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Enterocolitis ^† 1	2/36 (5.56%)	2	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Gastrointestinal haemorrhage ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Ileus ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	1/8 (12.50%)	1	0/35 (0.00%)	0
Mesenteric venous occlusion ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Nausea ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Pancreatitis ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	1/35 (2.86%)	1
Rectal haemorrhage ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Retroperitoneal haemorrhage ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Small intestinal obstruction ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Stomatitis ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Vomiting ^† 1	2/36 (5.56%)	2	0/7 (0.00%)	0	2/37 (5.41%)	2	0/8 (0.00%)	0	1/35 (2.86%)	1
General disorders
Chills ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Pyrexia ^† 1	2/36 (5.56%)	2	0/7 (0.00%)	0	2/37 (5.41%)	2	3/8 (37.50%)	3	4/35 (11.43%)	4
Systemic inflammatory response syndrome ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Hepatobiliary disorders
Acute hepatic failure ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Bile duct obstruction ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	2/35 (5.71%)	2
Cholecystitis ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Immune system disorders
Cytokine release syndrome ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	3/37 (8.11%)	3	0/8 (0.00%)	0	2/35 (5.71%)	2
Infections and infestations
Bacteraemia ^† 1	1/36 (2.78%)	1	1/7 (14.29%)	1	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Cellulitis ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Device related infection ^† 1	0/36 (0.00%)	0	1/7 (14.29%)	1	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Enterocolitis infectious ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	2
Liver abscess ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Neutropenic sepsis ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Pneumonia ^† 1	0/36 (0.00%)	0	1/7 (14.29%)	1	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Pneumonia staphylococcal ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Sepsis ^† 1	0/36 (0.00%)	0	1/7 (14.29%)	2	2/37 (5.41%)	2	0/8 (0.00%)	0	3/35 (8.57%)	3
Septic shock ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	2/8 (25.00%)	3	0/35 (0.00%)	0
Staphylococcal infection ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Urinary tract infection ^† 1	0/36 (0.00%)	0	1/7 (14.29%)	1	0/37 (0.00%)	0	0/8 (0.00%)	0	2/35 (5.71%)	2
Injury, poisoning and procedural complications
Hip fracture ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	1/8 (12.50%)	1	0/35 (0.00%)	0
Incorrect dose administered ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Infusion related reaction ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Transfusion reaction ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Investigations
Alanine aminotransferase increased ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Aspartate aminotransferase increased ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Metabolism and nutrition disorders
Dehydration ^† 1	2/36 (5.56%)	2	0/7 (0.00%)	0	2/37 (5.41%)	2	0/8 (0.00%)	0	1/35 (2.86%)	1
Failure to thrive ^† 1	0/36 (0.00%)	0	1/7 (14.29%)	1	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Musculoskeletal and connective tissue disorders
Myositis ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Nervous system disorders
Cerebrovascular accident ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	2/35 (5.71%)	2
Demyelinating polyneuropathy ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Facial nerve disorder ^† 1	0/36 (0.00%)	0	1/7 (14.29%)	1	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Haemorrhage intracranial ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
IIIrd nerve disorder ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Neuropathy peripheral ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	1/8 (12.50%)	1	0/35 (0.00%)	0
Toxic encephalopathy ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	1/8 (12.50%)	1	0/35 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	1/37 (2.70%)	1	1/8 (12.50%)	1	0/35 (0.00%)	0
Hypoxia ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	2/35 (5.71%)	2
Immune-mediated pneumonitis ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Pleural effusion ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Pneumonitis ^† 1	1/36 (2.78%)	1	1/7 (14.29%)	1	2/37 (5.41%)	2	0/8 (0.00%)	0	1/35 (2.86%)	1
Pneumothorax ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Pulmonary alveolar haemorrhage ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Pulmonary embolism ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	3/35 (8.57%)	3
Respiratory distress ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	1/8 (12.50%)	1	0/35 (0.00%)	0
Respiratory failure ^† 1	2/36 (5.56%)	2	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Skin and subcutaneous tissue disorders
Pseudocellulitis ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Rash ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Vascular disorders
Deep vein thrombosis ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	2/37 (5.41%)	2	0/8 (0.00%)	0	0/35 (0.00%)	0
Embolism ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
Haemoptysis ^† 1	1/36 (2.78%)	1	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	0/35 (0.00%)	0
Hypertension ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	1/37 (2.70%)	1	0/8 (0.00%)	0	0/35 (0.00%)	0
Malignant hypertension ^† 1	0/36 (0.00%)	0	0/7 (0.00%)	0	0/37 (0.00%)	0	0/8 (0.00%)	0	1/35 (2.86%)	1
1 Term from vocabulary, MedDRA (23.0) † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Gem/NP/Nivolumab		Gem/NP/APX005M (0.1 mg/kg)		Gem/NP/APX005M (0.3 mg/kg)		Gem/NP/Nivolumab/APX005M (0.1 mg/kg)		Gem/NP/Nivolumab/APX005M (0.3 mg/kg)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/36 (100.00%)		7/7 (100.00%)		36/37 (97.30%)		8/8 (100.00%)		35/35 (100.00%)
Blood and lymphatic system disorders
Anaemia ^† 1	22/36 (61.11%)		7/7 (100.00%)		22/37 (59.46%)		4/8 (50.00%)		18/35 (51.43%)
Haemolytic uraemic syndrome ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		2/8 (25.00%)		0/35 (0.00%)
Leukocytosis ^† 1	3/36 (8.33%)		0/7 (0.00%)		3/37 (8.11%)		1/8 (12.50%)		0/35 (0.00%)
Leukopenia ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		4/35 (11.43%)
Neutropenia ^† 1	8/36 (22.22%)		4/7 (57.14%)		12/37 (32.43%)		1/8 (12.50%)		6/35 (17.14%)
Pancytopenia ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Splenic vein thrombosis ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Thrombocytopenia ^† 1	9/36 (25.00%)		2/7 (28.57%)		11/37 (29.73%)		2/8 (25.00%)		15/35 (42.86%)
Febrile neutropenia ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Lymphopenia ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Cardiac disorders
Atrial fibrillation ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Palpitations ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Tachycardia ^† 1	2/36 (5.56%)		0/7 (0.00%)		4/37 (10.81%)		0/8 (0.00%)		6/35 (17.14%)
Ear and labyrinth disorders
Tinnitus ^† 1	0/36 (0.00%)		1/7 (14.29%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Endocrine disorders
Hyperthyroidism ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Hypothyroidism ^† 1	2/36 (5.56%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		4/35 (11.43%)
Eye disorders
Diplopia ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Dry eye ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Vision blurred ^† 1	2/36 (5.56%)		2/7 (28.57%)		0/37 (0.00%)		1/8 (12.50%)		5/35 (14.29%)
Visual acuity reduced ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Gastrointestinal disorders
Abdominal discomfort ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		1/8 (12.50%)		0/35 (0.00%)
Abdominal distension ^† 1	5/36 (13.89%)		0/7 (0.00%)		7/37 (18.92%)		2/8 (25.00%)		8/35 (22.86%)
Abdominal pain ^† 1	15/36 (41.67%)		0/7 (0.00%)		15/37 (40.54%)		3/8 (37.50%)		18/35 (51.43%)
Abdominal pain lower ^† 1	4/36 (11.11%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Abdominal pain upper ^† 1	7/36 (19.44%)		0/7 (0.00%)		4/37 (10.81%)		0/8 (0.00%)		0/35 (0.00%)
Anal fistula ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Ascites ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		4/35 (11.43%)
Constipation ^† 1	16/36 (44.44%)		2/7 (28.57%)		22/37 (59.46%)		4/8 (50.00%)		13/35 (37.14%)
Defaecation urgency ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Diarrhoea ^† 1	19/36 (52.78%)		3/7 (42.86%)		20/37 (54.05%)		3/8 (37.50%)		21/35 (60.00%)
Dry mouth ^† 1	3/36 (8.33%)		0/7 (0.00%)		4/37 (10.81%)		0/8 (0.00%)		3/35 (8.57%)
Dyspepsia ^† 1	2/36 (5.56%)		0/7 (0.00%)		5/37 (13.51%)		0/8 (0.00%)		5/35 (14.29%)
Eructation ^† 1	4/36 (11.11%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Flatulence ^† 1	2/36 (5.56%)		0/7 (0.00%)		3/37 (8.11%)		2/8 (25.00%)		4/35 (11.43%)
Gastrointestinal haemorrhage ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Gastrooesophageal reflux disease ^† 1	4/36 (11.11%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		4/35 (11.43%)
Haemorrhoids ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		2/8 (25.00%)		0/35 (0.00%)
Nausea ^† 1	26/36 (72.22%)		6/7 (85.71%)		33/37 (89.19%)		5/8 (62.50%)		29/35 (82.86%)
Oral pain ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Stomatitis ^† 1	5/36 (13.89%)		1/7 (14.29%)		2/37 (5.41%)		0/8 (0.00%)		5/35 (14.29%)
Vomiting ^† 1	14/36 (38.89%)		3/7 (42.86%)		23/37 (62.16%)		3/8 (37.50%)		20/35 (57.14%)
Small intestinal obstruction ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		3/35 (8.57%)
General disorders
Asthenia ^† 1	2/36 (5.56%)		3/7 (42.86%)		4/37 (10.81%)		3/8 (37.50%)		2/35 (5.71%)
Chest discomfort ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		3/35 (8.57%)
Chest pain ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Chills ^† 1	6/36 (16.67%)		5/7 (71.43%)		30/37 (81.08%)		6/8 (75.00%)		27/35 (77.14%)
Early satiety ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Face oedema ^† 1	0/36 (0.00%)		0/7 (0.00%)		3/37 (8.11%)		0/8 (0.00%)		0/35 (0.00%)
Fatigue ^† 1	27/36 (75.00%)		7/7 (100.00%)		29/37 (78.38%)		5/8 (62.50%)		29/35 (82.86%)
Gait disturbance ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Generalised oedema ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Influenza like illness ^† 1	2/36 (5.56%)		0/7 (0.00%)		6/37 (16.22%)		1/8 (12.50%)		2/35 (5.71%)
Infusion site pain ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Malaise ^† 1	3/36 (8.33%)		1/7 (14.29%)		3/37 (8.11%)		1/8 (12.50%)		0/35 (0.00%)
Medical device site joint swelling ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Mucosal inflammation ^† 1	3/36 (8.33%)		1/7 (14.29%)		5/37 (13.51%)		1/8 (12.50%)		5/35 (14.29%)
Oedema ^† 1	0/36 (0.00%)		3/7 (42.86%)		3/37 (8.11%)		1/8 (12.50%)		5/35 (14.29%)
Oedema peripheral ^† 1	15/36 (41.67%)		2/7 (28.57%)		22/37 (59.46%)		3/8 (37.50%)		13/35 (37.14%)
Pain ^† 1	3/36 (8.33%)		1/7 (14.29%)		2/37 (5.41%)		1/8 (12.50%)		0/35 (0.00%)
Peripheral swelling ^† 1	0/36 (0.00%)		2/7 (28.57%)		2/37 (5.41%)		0/8 (0.00%)		2/35 (5.71%)
Pyrexia ^† 1	16/36 (44.44%)		4/7 (57.14%)		29/37 (78.38%)		6/8 (75.00%)		24/35 (68.57%)
Hepatobiliary disorders
Hyperbilirubinaemia ^† 1	0/36 (0.00%)		0/7 (0.00%)		3/37 (8.11%)		0/8 (0.00%)		0/35 (0.00%)
Ocular icterus ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Immune system disorders
Cytokine release syndrome ^† 1	0/36 (0.00%)		5/7 (71.43%)		7/37 (18.92%)		2/8 (25.00%)		11/35 (31.43%)
Infections and infestations
Bronchitis ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Candida infection ^† 1	2/36 (5.56%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Cellulitis ^† 1	2/36 (5.56%)		1/7 (14.29%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Cystitis ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Enterocolitis infectious ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Folliculitis ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Oral candidiasis ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Otitis media ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Paronychia ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Pneumonia ^† 1	2/36 (5.56%)		2/7 (28.57%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Rhinitis ^† 1	0/36 (0.00%)		1/7 (14.29%)		7/37 (18.92%)		0/8 (0.00%)		4/35 (11.43%)
Sinusitis ^† 1	2/36 (5.56%)		0/7 (0.00%)		2/37 (5.41%)		1/8 (12.50%)		0/35 (0.00%)
Tooth infection ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Septic shock ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Upper respiratory tract infection ^† 1	0/36 (0.00%)		0/7 (0.00%)		6/37 (16.22%)		0/8 (0.00%)		0/35 (0.00%)
Urinary tract infection ^† 1	4/36 (11.11%)		2/7 (28.57%)		0/37 (0.00%)		0/8 (0.00%)		3/35 (8.57%)
Pancreas infection ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Injury, poisoning and procedural complications
Fall ^† 1	3/36 (8.33%)		0/7 (0.00%)		2/37 (5.41%)		1/8 (12.50%)		2/35 (5.71%)
Humerus fracture ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Infusion related reaction ^† 1	2/36 (5.56%)		1/7 (14.29%)		4/37 (10.81%)		1/8 (12.50%)		5/35 (14.29%)
Skin wound ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Traumatic haematoma ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Investigations
Alanine aminotransferase increased ^† 1	18/36 (50.00%)		4/7 (57.14%)		22/37 (59.46%)		1/8 (12.50%)		23/35 (65.71%)
Aspartate aminotransferase increased ^† 1	19/36 (52.78%)		4/7 (57.14%)		25/37 (67.57%)		2/8 (25.00%)		21/35 (60.00%)
Blood alkaline phosphatase increased ^† 1	9/36 (25.00%)		1/7 (14.29%)		16/37 (43.24%)		1/8 (12.50%)		14/35 (40.00%)
Blood bilirubin increased ^† 1	6/36 (16.67%)		2/7 (28.57%)		7/37 (18.92%)		2/8 (25.00%)		12/35 (34.29%)
Blood creatine phosphokinase increased ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Blood creatinine increased ^† 1	5/36 (13.89%)		0/7 (0.00%)		4/37 (10.81%)		3/8 (37.50%)		4/35 (11.43%)
Blood potassium decreased ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Lymphocyte count decreased ^† 1	6/36 (16.67%)		1/7 (14.29%)		9/37 (24.32%)		3/8 (37.50%)		6/35 (17.14%)
Neutrophil count decreased ^† 1	13/36 (36.11%)		4/7 (57.14%)		15/37 (40.54%)		2/8 (25.00%)		15/35 (42.86%)
Platelet count decreased ^† 1	13/36 (36.11%)		3/7 (42.86%)		13/37 (35.14%)		3/8 (37.50%)		17/35 (48.57%)
Platelet count increased ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Weight decreased ^† 1	11/36 (30.56%)		1/7 (14.29%)		4/37 (10.81%)		3/8 (37.50%)		4/35 (11.43%)
Weight increased ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
White blood cell count decreased ^† 1	10/36 (27.78%)		1/7 (14.29%)		7/37 (18.92%)		1/8 (12.50%)		6/35 (17.14%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	22/36 (61.11%)		3/7 (42.86%)		21/37 (56.76%)		3/8 (37.50%)		15/35 (42.86%)
Dehydration ^† 1	9/36 (25.00%)		1/7 (14.29%)		8/37 (21.62%)		3/8 (37.50%)		9/35 (25.71%)
Failure to thrive ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Fluid retention ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Hyperglycaemia ^† 1	4/36 (11.11%)		1/7 (14.29%)		3/37 (8.11%)		0/8 (0.00%)		3/35 (8.57%)
Hyperkalaemia ^† 1	2/36 (5.56%)		0/7 (0.00%)		3/37 (8.11%)		0/8 (0.00%)		2/35 (5.71%)
Hypoalbuminaemia ^† 1	7/36 (19.44%)		2/7 (28.57%)		3/37 (8.11%)		1/8 (12.50%)		4/35 (11.43%)
Hypocalcaemia ^† 1	3/36 (8.33%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		2/35 (5.71%)
Hypokalaemia ^† 1	5/36 (13.89%)		3/7 (42.86%)		6/37 (16.22%)		2/8 (25.00%)		9/35 (25.71%)
Hypomagnesaemia ^† 1	2/36 (5.56%)		1/7 (14.29%)		2/37 (5.41%)		1/8 (12.50%)		3/35 (8.57%)
Hyponatraemia ^† 1	4/36 (11.11%)		1/7 (14.29%)		12/37 (32.43%)		1/8 (12.50%)		9/35 (25.71%)
Hypophosphataemia ^† 1	2/36 (5.56%)		0/7 (0.00%)		4/37 (10.81%)		1/8 (12.50%)		3/35 (8.57%)
Malnutrition ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	6/36 (16.67%)		2/7 (28.57%)		4/37 (10.81%)		2/8 (25.00%)		4/35 (11.43%)
Back pain ^† 1	6/36 (16.67%)		2/7 (28.57%)		8/37 (21.62%)		0/8 (0.00%)		8/35 (22.86%)
Flank pain ^† 1	2/36 (5.56%)		0/7 (0.00%)		3/37 (8.11%)		0/8 (0.00%)		0/35 (0.00%)
Groin pain ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Limb discomfort ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Muscular weakness ^† 1	3/36 (8.33%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		3/35 (8.57%)
Myalgia ^† 1	3/36 (8.33%)		0/7 (0.00%)		10/37 (27.03%)		0/8 (0.00%)		10/35 (28.57%)
Neck pain ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Pain in extremity ^† 1	3/36 (8.33%)		0/7 (0.00%)		3/37 (8.11%)		2/8 (25.00%)		6/35 (17.14%)
Nervous system disorders
Amnesia ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Autoimmune neuropathy ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Dizziness ^† 1	7/36 (19.44%)		3/7 (42.86%)		6/37 (16.22%)		1/8 (12.50%)		9/35 (25.71%)
Dysarthria ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Dysgeusia ^† 1	4/36 (11.11%)		3/7 (42.86%)		4/37 (10.81%)		3/8 (37.50%)		7/35 (20.00%)
Headache ^† 1	8/36 (22.22%)		2/7 (28.57%)		12/37 (32.43%)		4/8 (50.00%)		4/35 (11.43%)
Hypoaesthesia ^† 1	0/36 (0.00%)		0/7 (0.00%)		4/37 (10.81%)		1/8 (12.50%)		0/35 (0.00%)
Lethargy ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Neuropathy peripheral ^† 1	10/36 (27.78%)		6/7 (85.71%)		17/37 (45.95%)		4/8 (50.00%)		9/35 (25.71%)
Paraesthesia ^† 1	0/36 (0.00%)		1/7 (14.29%)		5/37 (13.51%)		0/8 (0.00%)		2/35 (5.71%)
Peripheral motor neuropathy ^† 1	3/36 (8.33%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Peripheral sensory neuropathy ^† 1	8/36 (22.22%)		0/7 (0.00%)		7/37 (18.92%)		2/8 (25.00%)		7/35 (20.00%)
Presyncope ^† 1	4/36 (11.11%)		2/7 (28.57%)		2/37 (5.41%)		0/8 (0.00%)		3/35 (8.57%)
Taste disorder ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Tremor ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		2/35 (5.71%)
Syncope ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Psychiatric disorders
Adjustment disorder with anxiety ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Adjustment disorder with depressed mood ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Anxiety ^† 1	9/36 (25.00%)		1/7 (14.29%)		9/37 (24.32%)		0/8 (0.00%)		6/35 (17.14%)
Confusional state ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		5/35 (14.29%)
Delirium ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Depression ^† 1	6/36 (16.67%)		2/7 (28.57%)		7/37 (18.92%)		0/8 (0.00%)		6/35 (17.14%)
Hallucination ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Insomnia ^† 1	7/36 (19.44%)		2/7 (28.57%)		10/37 (27.03%)		2/8 (25.00%)		3/35 (8.57%)
Sleep disorder ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		3/35 (8.57%)
Renal and urinary disorders
Acute kidney injury ^† 1	0/36 (0.00%)		0/7 (0.00%)		4/37 (10.81%)		1/8 (12.50%)		0/35 (0.00%)
Chromaturia ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Dysuria ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Incontinence ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Micturition urgency ^† 1	0/36 (0.00%)		1/7 (14.29%)		2/37 (5.41%)		1/8 (12.50%)		0/35 (0.00%)
Pollakiuria ^† 1	0/36 (0.00%)		1/7 (14.29%)		4/37 (10.81%)		1/8 (12.50%)		0/35 (0.00%)
Renal failure ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Urinary retention ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Urinary tract pain ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		1/8 (12.50%)		0/35 (0.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	15/36 (41.67%)		1/7 (14.29%)		12/37 (32.43%)		2/8 (25.00%)		14/35 (40.00%)
Dysphonia ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Dyspnoea ^† 1	13/36 (36.11%)		4/7 (57.14%)		14/37 (37.84%)		2/8 (25.00%)		13/35 (37.14%)
Dyspnoea exertional ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		1/8 (12.50%)		3/35 (8.57%)
Epistaxis ^† 1	8/36 (22.22%)		3/7 (42.86%)		7/37 (18.92%)		0/8 (0.00%)		6/35 (17.14%)
Hiccups ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Hypoxia ^† 1	3/36 (8.33%)		3/7 (42.86%)		4/37 (10.81%)		2/8 (25.00%)		3/35 (8.57%)
Nasal congestion ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		4/35 (11.43%)
Oropharyngeal pain ^† 1	2/36 (5.56%)		0/7 (0.00%)		3/37 (8.11%)		0/8 (0.00%)		4/35 (11.43%)
Pleural effusion ^† 1	4/36 (11.11%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Pneumonitis ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		3/35 (8.57%)
Productive cough ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Pulmonary embolism ^† 1	0/36 (0.00%)		0/7 (0.00%)		3/37 (8.11%)		1/8 (12.50%)		4/35 (11.43%)
Pulmonary oedema ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Rhinorrhoea ^† 1	3/36 (8.33%)		0/7 (0.00%)		3/37 (8.11%)		0/8 (0.00%)		0/35 (0.00%)
Upper-airway cough syndrome ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		2/35 (5.71%)
Wheezing ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		1/8 (12.50%)		2/35 (5.71%)
Skin and subcutaneous tissue disorders
Alopecia ^† 1	14/36 (38.89%)		4/7 (57.14%)		17/37 (45.95%)		3/8 (37.50%)		12/35 (34.29%)
Dermatitis acneiform ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Dry skin ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Erythema ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		3/35 (8.57%)
Hyperhidrosis ^† 1	0/36 (0.00%)		0/7 (0.00%)		6/37 (16.22%)		0/8 (0.00%)		2/35 (5.71%)
Nail discolouration ^† 1	0/36 (0.00%)		2/7 (28.57%)		3/37 (8.11%)		0/8 (0.00%)		0/35 (0.00%)
Nail disorder ^† 1	2/36 (5.56%)		0/7 (0.00%)		3/37 (8.11%)		0/8 (0.00%)		0/35 (0.00%)
Night sweats ^† 1	0/36 (0.00%)		1/7 (14.29%)		4/37 (10.81%)		0/8 (0.00%)		3/35 (8.57%)
Pain of skin ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Pruritus ^† 1	5/36 (13.89%)		1/7 (14.29%)		16/37 (43.24%)		2/8 (25.00%)		13/35 (37.14%)
Rash ^† 1	17/36 (47.22%)		4/7 (57.14%)		11/37 (29.73%)		4/8 (50.00%)		17/35 (48.57%)
Rash erythematous ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Rash macular ^† 1	0/36 (0.00%)		0/7 (0.00%)		2/37 (5.41%)		0/8 (0.00%)		0/35 (0.00%)
Rash maculo-papular ^† 1	4/36 (11.11%)		1/7 (14.29%)		5/37 (13.51%)		1/8 (12.50%)		2/35 (5.71%)
Skin discolouration ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		1/8 (12.50%)		0/35 (0.00%)
Skin hyperpigmentation ^† 1	0/36 (0.00%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Urticaria ^† 1	0/36 (0.00%)		0/7 (0.00%)		5/37 (13.51%)		0/8 (0.00%)		9/35 (25.71%)
Vitiligo ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
Vascular disorders
Deep vein thrombosis ^† 1	2/36 (5.56%)		1/7 (14.29%)		5/37 (13.51%)		0/8 (0.00%)		4/35 (11.43%)
Flushing ^† 1	0/36 (0.00%)		0/7 (0.00%)		6/37 (16.22%)		0/8 (0.00%)		0/35 (0.00%)
Hot flush ^† 1	2/36 (5.56%)		0/7 (0.00%)		0/37 (0.00%)		0/8 (0.00%)		2/35 (5.71%)
Hypertension ^† 1	4/36 (11.11%)		1/7 (14.29%)		9/37 (24.32%)		1/8 (12.50%)		5/35 (14.29%)
Hypotension ^† 1	8/36 (22.22%)		3/7 (42.86%)		11/37 (29.73%)		3/8 (37.50%)		12/35 (34.29%)
Lymphoedema ^† 1	0/36 (0.00%)		1/7 (14.29%)		0/37 (0.00%)		0/8 (0.00%)		0/35 (0.00%)
1 Term from vocabulary, MedDRA (23.0) † 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:

Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States. Cancer Res. 2014 Jun 1;74(11):2913-21. doi: 10.1158/0008-5472.CAN-14-0155. Erratum In: Cancer Res. 2014 Jul 15;74(14):4006.

Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013 Oct 31;369(18):1691-703. doi: 10.1056/NEJMoa1304369. Epub 2013 Oct 16.

Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012 Mar 22;12(4):252-64. doi: 10.1038/nrc3239.

Bauer C, Kuhnemuth B, Duewell P, Ormanns S, Gress T, Schnurr M. Prevailing over T cell exhaustion: New developments in the immunotherapy of pancreatic cancer. Cancer Lett. 2016 Oct 10;381(1):259-68. doi: 10.1016/j.canlet.2016.02.057. Epub 2016 Mar 8.

Khong A, Nelson DJ, Nowak AK, Lake RA, Robinson BW. The use of agonistic anti-CD40 therapy in treatments for cancer. Int Rev Immunol. 2012 Aug;31(4):246-66. doi: 10.3109/08830185.2012.698338.

Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Padron LJ, Maurer DM, O'Hara MH, O'Reilly EM, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Yu JX, Pfeiffer SM, Spasic M, Xu J, Gherardini PF, Karakunnel J, Mick R, Alanio C, Byrne KT, Hollmann TJ, Moore JS, Jones DD, Tognetti M, Chen RO, Yang X, Salvador L, Wherry EJ, Dugan U, O'Donnell-Tormey J, Butterfield LH, Hubbard-Lucey VM, Ibrahim R, Fairchild J, Bucktrout S, LaVallee TM, Vonderheide RH. Sotigalimab and/or nivolumab with chemotherapy in first-line metastatic pancreatic cancer: clinical and immunologic analyses from the randomized phase 2 PRINCE trial. Nat Med. 2022 Jun;28(6):1167-1177. doi: 10.1038/s41591-022-01829-9. Epub 2022 Jun 3.

O'Hara MH, O'Reilly EM, Varadhachary G, Wolff RA, Wainberg ZA, Ko AH, Fisher G, Rahma O, Lyman JP, Cabanski CR, Mick R, Gherardini PF, Kitch LJ, Xu J, Samuel T, Karakunnel J, Fairchild J, Bucktrout S, LaVallee TM, Selinsky C, Till JE, Carpenter EL, Alanio C, Byrne KT, Chen RO, Trifan OC, Dugan U, Horak C, Hubbard-Lucey VM, Wherry EJ, Ibrahim R, Vonderheide RH. CD40 agonistic monoclonal antibody APX005M (sotigalimab) and chemotherapy, with or without nivolumab, for the treatment of metastatic pancreatic adenocarcinoma: an open-label, multicentre, phase 1b study. Lancet Oncol. 2021 Jan;22(1):118-131. doi: 10.1016/S1470-2045(20)30532-5.

Layout table for additonal information

Responsible Party:	Parker Institute for Cancer Immunotherapy
ClinicalTrials.gov Identifier:	NCT03214250
Other Study ID Numbers:	PICI0002 UPCC 11217 ( Other Identifier: University of Pennsylvania )
First Submitted:	June 9, 2017
First Posted:	July 11, 2017
Results First Submitted:	March 25, 2022
Results First Posted:	August 11, 2022
Last Update Posted:	December 23, 2022

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