Trial Outcomes & Findings for A Phase 2 Study of Pembrolizumab (MK-3475) in Combination With Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer (NCT NCT02260440)

Last Updated: 2019-09-17

Results Overview

The objective response rate is estimated by the proportion (percentage) of participants with the best response of complete response (CR), or partial response (PR) by RECIST 1.1 criteria, with corresponding exact 95% confidence limits being reported. Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Up to 14 months

Results posted on

2019-09-17

Participant Flow

Participant milestones

Participant milestones
Measure	Pembrolizumab and Azacitidine 200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days. Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.
Overall Study STARTED	31
Overall Study COMPLETED	31
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Phase 2 Study of Pembrolizumab (MK-3475) in Combination With Azacitidine in Subjects With Chemo-refractory Metastatic Colorectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab and Azacitidine n=31 Participants 200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days. Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.
Age, Continuous	61 years n=5 Participants
Sex: Female, Male Female	14 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 14 months

Population: Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).

Outcome measures

Outcome measures
Measure	Pembrolizumab and Azacitidine n=30 Participants 200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days. Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.
Objective Response Rate (ORR)	3 percentage of participants Interval 1.0 to 17.0

SECONDARY outcome

Timeframe: Up to 2 years

Population: Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).

Progression-free Survival (PFS) (median) was determined using the number of months measured from the initial date of treatment to the date of documented progression, or the date of death (in the absence of progression) of participants. 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.

Outcome measures

Outcome measures
Measure	Pembrolizumab and Azacitidine n=30 Participants 200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days. Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.
Progression-free Survival (PFS)	2.1 months Interval 1.8 to 2.8

SECONDARY outcome

Timeframe: Up to 2 years

Population: Participants who received at least one dose of study therapy (median, 3 cycles; range, 1-8).

Overall Survival (OS) (median) was determined using the number of months measured from the initial date of treatment to the recorded date of death of participants.

Outcome measures

Outcome measures
Measure	Pembrolizumab and Azacitidine n=30 Participants 200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days. Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.
Overall Survival (OS)	6.2 months Interval 3.5 to 8.7

Adverse Events

Pembrolizumab and Azacitidine

Serious events: 13 serious events

Other events: 30 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Pembrolizumab and Azacitidine n=30 participants at risk 200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days. Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.
Blood and lymphatic system disorders Anemia	3.3% 1/30
Cardiac disorders Sinus tachycardia	3.3% 1/30
Gastrointestinal disorders Abdominal distension	6.7% 2/30
General disorders Death NOS	3.3% 1/30
General disorders Fatigue	3.3% 1/30
Hepatobiliary disorders Hepatobiliary disorders - Other, specify	3.3% 1/30
Infections and infestations Rash pustular	3.3% 1/30
Investigations Alanine aminotransferase increased	3.3% 1/30
Investigations Blood bilirubin increased	3.3% 1/30
Metabolism and nutrition disorders Dehydration	3.3% 1/30
Metabolism and nutrition disorders Hyponatremia	3.3% 1/30
Musculoskeletal and connective tissue disorders Generalized muscle weakness	3.3% 1/30
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	10.0% 3/30
Nervous system disorders Lethargy	3.3% 1/30
Nervous system disorders Stroke	3.3% 1/30
Psychiatric disorders Confusion	3.3% 1/30
Renal and urinary disorders Acute kidney injury	3.3% 1/30
Renal and urinary disorders Hematuria	3.3% 1/30
Renal and urinary disorders Renal and urinary disorders - Other, specify	3.3% 1/30
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.3% 1/30

Other adverse events

Other adverse events
Measure	Pembrolizumab and Azacitidine n=30 participants at risk 200 mg of Pembrolizumab was administered intravenously over 30 minutes on Day 1 of every 21 day cycle. 100 mg of Azacitidine was given daily via subcutaneous injection on days 1-5 every 21 days. Treatment continued for 9 cycles (about 27 weeks) or until there was an evidence of progression of disease (PD) or unacceptable toxicity before the completion of the planned 9 cycles.
Blood and lymphatic system disorders Anemia	60.0% 18/30
Cardiac disorders Sinus bradycardia	10.0% 3/30
Gastrointestinal disorders Diarrhea	6.7% 2/30
Gastrointestinal disorders Gastrointestinal disorders - Other, specify	10.0% 3/30
Gastrointestinal disorders Vomiting	10.0% 3/30
Gastrointestinal disorders Abdominal pain	13.3% 4/30
Gastrointestinal disorders Constipation	23.3% 7/30
Gastrointestinal disorders Nausea	30.0% 9/30
General disorders Fever	6.7% 2/30
General disorders General disorders and administration site conditions - Other, specify	10.0% 3/30
General disorders Pain	10.0% 3/30
General disorders Fatigue	40.0% 12/30
Investigations Creatinine increased	13.3% 4/30
Investigations Neutrophil count decreased	13.3% 4/30
Investigations Platelet count decreased	13.3% 4/30
Investigations Blood bilirubin increased	16.7% 5/30
Investigations White blood cell decreased	23.3% 7/30
Investigations Alanine aminotransferase increased	30.0% 9/30
Investigations Lymphocyte count decreased	30.0% 9/30
Investigations Aspartate aminotransferase increased	36.7% 11/30
Investigations Alkaline phosphatase increased	46.7% 14/30
Metabolism and nutrition disorders Anorexia	6.7% 2/30
Metabolism and nutrition disorders Hypokalemia	6.7% 2/30
Metabolism and nutrition disorders Hypophosphatemia	6.7% 2/30
Metabolism and nutrition disorders Metabolism and nutrition disorders - Other, specify	10.0% 3/30
Metabolism and nutrition disorders Hyperkalemia	13.3% 4/30
Metabolism and nutrition disorders Hypernatremia	13.3% 4/30
Metabolism and nutrition disorders Hypocalcemia	23.3% 7/30
Metabolism and nutrition disorders Hyponatremia	53.3% 16/30
Metabolism and nutrition disorders Hypoalbuminemia	60.0% 18/30
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other, specify	6.7% 2/30
Nervous system disorders Headache	6.7% 2/30
Psychiatric disorders Anxiety	6.7% 2/30
Respiratory, thoracic and mediastinal disorders Hypoxia	6.7% 2/30
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders - Other, specify	10.0% 3/30

Additional Information

Anuradha Krishnamurthy, MD

UPMC Hillman Cancer Center

Phone: 412-623-3283

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place