Pembrolizumab in Combination With Ibrutinib for Advanced, Refractory Colorectal Cancers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03332498

Recruitment Status : Completed

First Posted : November 6, 2017

Results First Posted : January 22, 2021

Last Update Posted : June 3, 2022

View this study on the modernized ClinicalTrials.gov

Sponsor:

Collaborators:

Janssen Scientific Affairs, LLC

Merck Sharp & Dohme LLC

Information provided by (Responsible Party):

H. Lee Moffitt Cancer Center and Research Institute

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Colon Cancer Colorectal Cancer Colorectal Carcinoma Colon Disease
Interventions	Drug: Pembrolizumab Drug: Ibrutinib
Enrollment	40

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Phase 1 Cohort 0: Dose Escalation (Pembrolizumab and Ibrutinib)	Phase 1 Cohort 1: Dose Escalation (Pembrolizumab and Ibrutinib)	Phase 2: Treatment at RP2D
Arm/Group Description	Pembrolizumab intravenously (IV): 2...	Pembrolizumab intravenously (IV): 2...	Phase 2: Treatment at Recommended P...
Arm/Group Description	Pembrolizumab intravenously (IV): 200 mg every 3 weeks (Q3W). Ibrutinib by mouth (PO): Phase I Dose Escalation at 420 mg daily.	Pembrolizumab intravenously (IV): 200 mg every 3 weeks (Q3W). Ibrutinib by mouth (PO): Phase I Dose Escalation at 560 mg daily	Phase 2: Treatment at Recommended Phase 2 Dose (RP2D) - 200 mg Pembrolizumab and 560 mg Ibrutinib Pembrolizumab: 200 milligrams of pembrolizumab will be given through an IV (intravenously) for about thirty minutes. Pembrolizumab is an anti-PD1 that functions by inhibiting checkpoint inhibition and reversing T cell suppression. Ibrutinib: Ibrutinib oral capsules every day starting on cycle 1, day 1. Ibrutinib is primarily a BTK inhibitor which has been approved for the treatment of several hematologic malignancies.
Period Title: Overall Study
Started	4	4	32
Completed	4	4	30
Not Completed	0	0	2
Reason Not Completed
Severe illness prior to Day 1 of treatment	0	0	2

Baseline Characteristics

Arm/Group Title		Phase 1 Cohort 0: Dose Escalation (Pembrolizumab and Ibrutinib)	Phase 1 Cohort 1: Dose Escalation (Pembrolizumab and Ibrutinib)	Phase 2: Treatment at RP2D	Total
Arm/Group Description		Pembrolizumab intravenously (IV): 2...	Pembrolizumab intravenously (IV): 2...	Phase 2: Treatment at Recommended P...	Total of all reporting groups
Arm/Group Description		Pembrolizumab intravenously (IV): 200 mg every 3 weeks (Q3W). Ibrutinib by mouth (PO): Phase I Dose Escalation at 420 mg daily.	Pembrolizumab intravenously (IV): 200 mg every 3 weeks (Q3W). Ibrutinib by mouth (PO): Phase I Dose Escalation at 560 mg daily	Phase 2: Treatment at Recommended Phase 2 Dose (RP2D) - 200 mg Pembrolizumab and 560 mg Ibrutinib Pembrolizumab: 200 milligrams of pembrolizumab will be given through an IV (intravenously) for about thirty minutes. Pembrolizumab is an anti-PD1 that functions by inhibiting checkpoint inhibition and reversing T cell suppression. Ibrutinib: Ibrutinib oral capsules every day starting on cycle 1, day 1. Ibrutinib is primarily a BTK inhibitor which has been approved for the treatment of several hematologic malignancies.	Total of all reporting groups
Overall Number of Baseline Participants		4	4	32	40
Baseline Analysis Population Description		...
Baseline Analysis Population Description		All participants who consented to study.
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4 participants	4 participants	32 participants	40 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	3 75.0%	4 100.0%	24 75.0%	31 77.5%
	>=65 years	1 25.0%	0 0.0%	8 25.0%	9 22.5%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4 participants	4 participants	32 participants	40 participants
	Female	0 0.0%	2 50.0%	15 46.9%	17 42.5%
	Male	4 100.0%	2 50.0%	17 53.1%	23 57.5%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4 participants	4 participants	32 participants	40 participants
	Hispanic or Latino	0 0.0%	0 0.0%	1 3.1%	1 2.5%
	Not Hispanic or Latino	4 100.0%	4 100.0%	29 90.6%	37 92.5%
	Unknown or Not Reported	0 0.0%	0 0.0%	2 6.3%	2 5.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	4 participants	4 participants	32 participants	40 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	1 3.1%	1 2.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	5 15.6%	5 12.5%
	White	4 100.0%	4 100.0%	25 78.1%	33 82.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	1 3.1%	1 2.5%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	4 participants	4 participants	32 participants	40 participants
United States		4	4	32	40

Outcome Measures

1.Primary Outcome


Title	Phase I - Recommended Phase II Dose (RP2D)
Description	Standard 3+3 Design: The first cohort will enroll a minimum of 3 parti...
Description	Standard 3+3 Design: The first cohort will enroll a minimum of 3 participants, according to a standard 3+3 design. If 0 out of the first 3 participants in the first cohort experience a dose-limiting toxicity (DLT), then dose escalation will continue as planned. If 1 out of the first 3 participants experience a DLT, then the cohort will be expanded to a total of 6 participants, and if no more than 1 out of 6 participants experiences a DLT in a given dose cohort, dose escalation will continue as planned. If ≥ 2 DLTs are observed in the first dose cohort, the principle investigator will discuss with Janssen on how to proceed. The DLT evaluation period will be defined as the time from the first dose of pembrolizumab and ibrutinib to 42 days after the first dose or if a participant experiences a DLT within this time period.
Time Frame	42 days post first dose

Outcome Measure Data

Analysis Population Description

All participants in Phase 1 portion of study who received at least one dose of study drugs


Arm/Group Title	Pembrolizumab and Ibrutinib
Arm/Group Description:	Pembrolizumab intravenously (IV): 2...
Arm/Group Description:	Pembrolizumab intravenously (IV): 200 mg every 3 weeks (Q3W). Ibrutinib by mouth (PO): Phase I Dose Escalation at doses of 420 mg daily (cohort 0) and 560 mg daily (cohort 1) Pembrolizumab: 200 milligrams of pembrolizumab will be given through an IV (intravenously) for about thirty minutes. Pembrolizumab is an anti-PD1 that functions by inhibiting checkpoint inhibition and reversing T cell suppression. Ibrutinib: Ibrutinib oral capsules every day starting on cycle 1, day 1. Ibrutinib is primarily a BTK inhibitor which has been approved for the treatment of several hematologic malignancies.
Overall Number of Participants Analyzed	8
Measure Type: Number Unit of Measure: mg
	560

2.Primary Outcome


Title	Phase II - Disease Control Rate at 4 Months
Description	Percentage of participants who achieved disease control at 4 months. D...
Description	Percentage of participants who achieved disease control at 4 months. Disease control rate = Complete Response (CR) + Partial Response (PR) + Stable Disease (SD). Tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and RECIST based immune-related response criteria (irRC).
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

All participants in Phase 2 portion who received at least one dose of study drugs.


Arm/Group Title	Phase 2: Treatment at RP2D
Arm/Group Description:	Phase 2: Treatment at Recommended P...
Arm/Group Description:	Phase 2: Treatment at Recommended Phase 2 Dose (RP2D) - 200 mg Pembrolizumab and 560 mg Ibrutinib Pembrolizumab: 200 milligrams of pembrolizumab will be given through an IV (intravenously) for about thirty minutes. Pembrolizumab is an anti-PD1 that functions by inhibiting checkpoint inhibition and reversing T cell suppression. Ibrutinib: Ibrutinib oral capsules every day starting on cycle 1, day 1. Ibrutinib is primarily a BTK inhibitor which has been approved for the treatment of several hematologic malignancies.
Overall Number of Participants Analyzed	31
Measure Type: Number Unit of Measure: percentage of participants
	13

Adverse Events

Time Frame	1 year, 5 months
Adverse Event Reporting Description	Includes only participants who received at least one dose of study drugs.

Arm/Group Title	Phase 1 Cohort 0: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 1 Cohort 1: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 2: Treatment at RP2D
Arm/Group Description	Pembrolizumab intravenously (IV): 2...		Pembrolizumab intravenously (IV): 2...		Phase 2: Treatment at Recommended P...
Arm/Group Description	Pembrolizumab intravenously (IV): 200 mg every 3 weeks (Q3W). Ibrutinib by mouth (PO): Phase I Dose Escalation at 420 mg daily.		Pembrolizumab intravenously (IV): 200 mg every 3 weeks (Q3W). Ibrutinib by mouth (PO): Phase I Dose Escalation at 560 mg daily		Phase 2: Treatment at Recommended Phase 2 Dose (RP2D) - 200 mg Pembrolizumab and 560 mg Ibrutinib Pembrolizumab: 200 milligrams of pembrolizumab will be given through an IV (intravenously) for about thirty minutes. Pembrolizumab is an anti-PD1 that functions by inhibiting checkpoint inhibition and reversing T cell suppression. Ibrutinib: Ibrutinib oral capsules every day starting on cycle 1, day 1. Ibrutinib is primarily a BTK inhibitor which has been approved for the treatment of several hematologic malignancies.
All-Cause Mortality
	Phase 1 Cohort 0: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 1 Cohort 1: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 2: Treatment at RP2D
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	3/4 (75.00%)		4/4 (100.00%)		26/32 (81.25%)
Serious Adverse Events Serious Adverse Events
	Phase 1 Cohort 0: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 1 Cohort 1: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 2: Treatment at RP2D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/4 (50.00%)		3/4 (75.00%)		13/32 (40.63%)
Blood and lymphatic system disorders
Anemia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)		2/32 (6.25%)	3
Cardiac disorders
Sinus tachycardia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Atrial fibrillation ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Chest pain -cardiac ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Gastrointestinal disorders
Rectal hemorrhage ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Nausea ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Vomiting ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Abdominal Pain ^† 1	1/4 (25.00%)	1	2/4 (50.00%)	2	1/32 (3.13%)	2
Ascites ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Constipation ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Abdominal distension ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Bowel Obstruction ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	2	0/32 (0.00%)	0
Low colostomy output ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
General disorders
Rib pain ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Edma limbs ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Fever ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Fatigue ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Hepatobiliary disorders
Cholangitis ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Cholecystitis ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Infections and infestations
Bronchial infection ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	2
Infections and Infestations - Other ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Urinary tract infection-Pyelonephritis ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Investigations
Blood bilirubin increased ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/32 (3.13%)	1
Creatinine increased ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Metabolism and nutrition disorders
Dehydration ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Flank pain ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Disease progression ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Neoplasms benign, malignant and unspecified-Other ^† 1 [1]	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Nervous system disorders
Dysarthria ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Encephalopathy ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Renal and urinary disorders
Acute kidney injury ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Renal calculi ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	3
Pneumonia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Vascular disorders
Hypotension ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	3/32 (9.38%)	3
Thromboembolic event ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
1 Term from vocabulary, CTCAE (4.0) † Indicates events were collected by systematic assessment [1] brain tumor
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Phase 1 Cohort 0: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 1 Cohort 1: Dose Escalation (Pembrolizumab and Ibrutinib)		Phase 2: Treatment at RP2D
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/4 (100.00%)		4/4 (100.00%)		29/32 (90.63%)
Blood and lymphatic system disorders
Anemia ^† 1	3/4 (75.00%)	7	3/4 (75.00%)	22	13/32 (40.63%)	21
Leukocytosis ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/32 (3.13%)	1
Cardiac disorders
Sinus tachycardia ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/32 (3.13%)	1
Atrial fibrillation ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Chest pain -cardiac ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Eye disorders
Blurred vision ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Dry eye ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Eye disorders - Other ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Eye pain ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^† 1	2/4 (50.00%)	3	1/4 (25.00%)	1	11/32 (34.38%)	15
Diarrhea ^† 1	2/4 (50.00%)	2	1/4 (25.00%)	1	10/32 (31.25%)	11
Nausea ^† 1	3/4 (75.00%)	3	0/4 (0.00%)	0	8/32 (25.00%)	9
Vomiting ^† 1	0/4 (0.00%)	0	2/4 (50.00%)	3	7/32 (21.88%)	7
Gastrointestinal disorders - Other ^† 1	1/4 (25.00%)	2	1/4 (25.00%)	1	6/32 (18.75%)	7
Constipation ^† 1	1/4 (25.00%)	1	2/4 (50.00%)	3	3/32 (9.38%)	4
Dyspepsia ^† 1	1/4 (25.00%)	2	0/4 (0.00%)	0	3/32 (9.38%)	3
Ascites ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Gastroesophageal reflux disease ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	2/32 (6.25%)	2
Abdominal distension ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	3
Dysphagia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Oral pain ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	3
Flatulence ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Lip pain ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Mucositis oral ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Oral hemorrhage ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	4
Rectal hemorrhage ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	2
Stomach pain ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	2	0/32 (0.00%)	0
General disorders
Fatigue ^† 1	1/4 (25.00%)	1	3/4 (75.00%)	4	13/32 (40.63%)	15
Fever ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	1	5/32 (15.63%)	7
Edema limbs ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	5/32 (15.63%)	5
General disorders and administration site conditions - Other ^† 1	2/4 (50.00%)	4	1/4 (25.00%)	1	1/32 (3.13%)	1
Chills ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Flu like symptoms ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	3	1/32 (3.13%)	1
Pain ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	1/32 (3.13%)	1
Irritability ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Non-cardiac chest pain ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Infections and infestations
Urinary tract infection ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	6/32 (18.75%)	7
Upper respiratory infection ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	2/32 (6.25%)	2
Infections and infestations - Other ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Sinusitis ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Rash pustular ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Injury, poisoning and procedural complications
Bruising ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	2
Gastrointestinal anastomotic leak ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Injury, poisoning and procedural complications -Other ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Investigations
Alkaline phosphatase increased ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	11/32 (34.38%)	11
Alanine aminotransferase increased ^† 1	0/4 (0.00%)	0	2/4 (50.00%)	2	8/32 (25.00%)	12
Aspartate aminotransferase increased ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	3	9/32 (28.13%)	9
Blood bilirubin increased ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	3	8/32 (25.00%)	11
Platelet count decreased ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	5/32 (15.63%)	5
CPK increased ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	3/32 (9.38%)	4
Creatinine increased ^† 1	2/4 (50.00%)	2	0/4 (0.00%)	0	2/32 (6.25%)	3
Lipase increased ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	4/32 (12.50%)	4
Lymphocyte count decreased ^† 1	1/4 (25.00%)	2	1/4 (25.00%)	1	2/32 (6.25%)	3
Serum amylase increased ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	2/32 (6.25%)	3
Electrocardiogram QT corrected interval prolonged ^† 1	1/4 (25.00%)	2	0/4 (0.00%)	0	1/32 (3.13%)	1
INR increased ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Weight gain ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	1/32 (3.13%)	1
Weight loss ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
GGT increased ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Investigations - Other ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	2
Metabolism and nutrition disorders
Hyponatremia ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	9/32 (28.13%)	12
Anorexia ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	8/32 (25.00%)	8
Hyperglycemia ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	7/32 (21.88%)	8
Hypoalbuminemia ^† 1	1/4 (25.00%)	2	1/4 (25.00%)	3	6/32 (18.75%)	6
Dehydration ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	4/32 (12.50%)	5
Hyperkalemia ^† 1	2/4 (50.00%)	5	1/4 (25.00%)	1	2/32 (6.25%)	2
Hypocalcemia ^† 1	2/4 (50.00%)	4	0/4 (0.00%)	0	3/32 (9.38%)	3
Hypokalemia ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	2	3/32 (9.38%)	3
Hypomagnesemia ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	1	2/32 (6.25%)	2
Hypercalcemia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	3/32 (9.38%)	3
Hypermagnesemia ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/32 (3.13%)	1
Hypophosphatemia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Hypoglycemia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	4/32 (12.50%)	4
Myalgia ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	5/32 (15.63%)	8
Arthralgia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	4/32 (12.50%)	6
Musculoskeletal and connective tissue disorders - Other ^† 1	1/4 (25.00%)	1	2/4 (50.00%)	2	1/32 (3.13%)	4
Pain in extremity ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	3/32 (9.38%)	3
Arthritis ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/32 (3.13%)	1
Flank pain ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Generalized muscle weakness ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Muscle weakness lower limb ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Neck pain ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified -Other ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Nervous system disorders
Headache ^† 1	2/4 (50.00%)	4	1/4 (25.00%)	1	7/32 (21.88%)	10
Dizziness ^† 1	1/4 (25.00%)	2	0/4 (0.00%)	0	4/32 (12.50%)	4
Peripheral sensory neuropathy ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	3/32 (9.38%)	3
Parasthesia ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	1/32 (3.13%)	1
Dysgeusia ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Encephalopathy ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Memory impairment ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Nervous system disorders - Other ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	0/32 (0.00%)	0
Peripheral motor neuropathy ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Seizure ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Psychiatric disorders
Anxiety ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	1	1/32 (3.13%)	1
Insomnia ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	2/32 (6.25%)	2
Depression ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	2/32 (6.25%)	2
Restlessness ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/32 (3.13%)	1
Agitation ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	3
Confusion ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Renal and urinary disorders
Acute kidney injury ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	1	0/32 (0.00%)	0
Renal and urinary disorders - Other ^† 1	0/4 (0.00%)	0	2/4 (50.00%)	4	0/32 (0.00%)	0
Cystitis noninfective ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Proteinuria ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Urinary frequency ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Urinary incontinence ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Urinary tract obstruction ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Urinary urgency ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Urine discoloration ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Reproductive system and breast disorders
Female genital tract fistula ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Vaginal discharge ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	2/4 (50.00%)	2	1/4 (25.00%)	1	7/32 (21.88%)	7
Dyspnea ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	2	5/32 (15.63%)	5
Respiratory, thoracic and mediastinal disorders - Other ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	3/32 (9.38%)	3
Hypoxia ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	1/32 (3.13%)	1
Epistaxis ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Hiccups ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Pleural effusion ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Pulmonary edema ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Respiratory failure ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Sleep apnea ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	8/32 (25.00%)	11
Pruritus ^† 1	1/4 (25.00%)	1	0/4 (0.00%)	0	2/32 (6.25%)	2
Skin and subcutaneous tissue disorders - Other ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	3/32 (9.38%)	3
Bullous dermatitis ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Dry skin ^† 1	0/4 (0.00%)	0	1/4 (25.00%)	1	0/32 (0.00%)	0
Hyperhidrosis ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Rash acneiform ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
Vascular disorders
Hypertension ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	2	8/32 (25.00%)	11
Hypotension ^† 1	1/4 (25.00%)	1	1/4 (25.00%)	1	3/32 (9.38%)	3
Hot flashes ^† 1	2/4 (50.00%)	3	0/4 (0.00%)	0	1/32 (3.13%)	1
Thromboembolic event ^† 1	0/4 (0.00%)	0	0/4 (0.00%)	0	1/32 (3.13%)	1
1 Term from vocabulary, CTCAE (4.0) † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Richard D. Kim, MD
Organization:	Moffitt Cancer Center
Phone:	813-745-1277
EMail:	Richard.Kim@moffitt.org

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

Kim DW, Tan E, Zhou JM, Schell MJ, Martinez M, Yu J, Carballido E, Mehta R, Strosberg J, Imanirad I, Kim RD. A phase 1/2 trial of ibrutinib in combination with pembrolizumab in patients with mismatch repair proficient metastatic colorectal cancer. Br J Cancer. 2021 May;124(11):1803-1808. doi: 10.1038/s41416-021-01368-z. Epub 2021 Apr 7.

Layout table for additonal information

Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT03332498
Other Study ID Numbers:	MCC-19091
First Submitted:	November 2, 2017
First Posted:	November 6, 2017
Results First Submitted:	December 4, 2020
Results First Posted:	January 22, 2021
Last Update Posted:	June 3, 2022

To Top