NCT02375672

Study of Pembrolizumab in Combination With Chemotherapy for Patients With Advanced Colorectal Cancer

Completed Phase 2 Results posted Last updated 16 February 2022

What this trial tests

Phase 2 trial testing Pembrolizumab in Colorectal Cancer in 30 participants. Completed in 8 October 2020.

Timeline

28 May 2015

Primary endpoint
8 October 2020

8 October 2020

Quick facts

Lead sponsor	Hoosier Cancer Research Network
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	28 May 2015
Primary completion	8 October 2020
Estimated completion	8 October 2020
Sites	3 locations across United States

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →
• mFOLFOX6

Conditions studied

• Colorectal Cancer — all drugs for Colorectal Cancer →

Sponsor

Hoosier Cancer Research Network

Who can join

18 and older, any sex, with Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Median Progression Free Survival (mPFS) Primary · From time of registration to the time of documented progression per RECIST 1.1 or subject death (estimate 14 months)

Determine if pembrolizumab (MK-3475) in combination with chemotherapy improves median progression free survival (mPFS) compared to historical standards. Response Criteria - Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesion

Group	Value	95% CI
Pembrolizumab (MK-3475) + mFOLFOX6	8.8	7.7 – 11.3

Disease Assessment for Objective Response Rate (ORR) Secondary · Begin C1D1 and every 8 weeks thereafter (up to 24 months)

To determine the number of patients who achieve complete response and partial response per irRC criteria.

Group	Value	95% CI
Pembrolizumab (MK-3475) + mFOLFOX6	17

Disease Assessment for Disease Control Rate Secondary · Begin C1D1 and every 8 weeks thereafter (up to 24 months) per RECIST 1.1 criteria

Disease control rate (DCR), defined as the sum of subjects with complete response, partial response and stable disease per RECIST 1.1 criteria.

Group	Value	95% CI
Pembrolizumab (MK-3475) + mFOLFOX6	30

Overall Survival (OS) Secondary · Subject should be followed from time of registration till the time of subject death up to a maximum 35.5 months

Overall Survival (OS) reported as number of subject alive at a median followup time of 19.9 months.

Group	Value	95% CI
Pembrolizumab (MK-3475) + mFOLFOX6	20
Pembrolizumab (MK-3475) + mFOLFOX6	10

Number of Patients With Grade 3 or Higher Treatment Related Adverse Event Secondary · Begin C1D1 and very 2 weeks (Day 1) for up to 24 months

To assess safety and tolerability of mFOLFOX6 and pembrolizumab (MK-3475) combination chemotherapy in patients with advanced colorectal cancer per CTCAE v4.0. Events are considered related if they assessed possible, probable or definite with study drug.

Group	Value	95% CI
Pembrolizumab (MK-3475) + mFOLFOX6	15

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events (AEs) was reported from the time of consent and until 30 days after last dose of study drug up to a maximum 108 weeks.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab (MK-3475) + mFOLFOX6

Serious: 7/30 (23%)

Deaths: 10/30

Serious adverse events (10 terms)

Reaction	System	Pembrolizumab (MK-3475) + …
FEBRILE NEUTROPENIA	Blood and lymphatic system disorders	—
ANAPHYLAXIS	Immune system disorders	—
COLITIS	Gastrointestinal disorders	—
DIARRHEA	Gastrointestinal disorders	—
ENDOCRINE DISORDERS	Endocrine disorders	—
FEVER	General disorders	—
GASTROINTESTINAL DISORDERS	Gastrointestinal disorders	—
NAUSEA	Gastrointestinal disorders	—
THROMBOEMBOLIC EVENT	Vascular disorders	—
VOMITING	Gastrointestinal disorders	—

Other adverse events (103 terms — click to expand)

Reaction	System	Pembrolizumab (MK-3475) + …
NAUSEA	Gastrointestinal disorders	—
PERIPHERAL SENSORY NEUROPATHY	Nervous system disorders	—
FATIGUE	General disorders	—
DIARRHEA	Gastrointestinal disorders	—
ABDOMINAL PAIN	Gastrointestinal disorders	—
CONSTIPATION	Gastrointestinal disorders	—
MUCOSITIS ORAL	Gastrointestinal disorders	—
NEUTROPHIL COUNT DECREASED	Investigations	—
VOMITING	Gastrointestinal disorders	—
ALANINE AMINOTRANSFERASE INCREASED	Investigations	—
ANOREXIA	Metabolism and nutrition disorders	—
HYPERGLYCEMIA	Metabolism and nutrition disorders	—
PLATELET COUNT DECREASED	Investigations	—
ASPARTATE AMINOTRANSFERASE INCREASED	Investigations	—
BLOOD BILIRUBIN INCREASED	Investigations	—
DYSGEUSIA	Nervous system disorders	—
HEADACHE	Nervous system disorders	—
NERVOUS SYSTEM DISORDERS	Nervous system disorders	—
ALKALINE PHOSPHATASE INCREASED	Investigations	—
ANEMIA	Blood and lymphatic system disorders	—
DYSPEPSIA	Gastrointestinal disorders	—
FEVER	General disorders	—
RECTAL HEMORRHAGE	Gastrointestinal disorders	—
WEIGHT LOSS	Investigations	—
WHITE BLOOD CELL DECREASED	Investigations	—
CHILLS	General disorders	—
HYPOKALEMIA	Metabolism and nutrition disorders	—
PARESTHESIA	Nervous system disorders	—
RASH ACNEIFORM	Skin and subcutaneous tissue disorders	—
RASH MACULO-PAPULAR	Skin and subcutaneous tissue disorders	—
ALOPECIA	Skin and subcutaneous tissue disorders	—
BACK PAIN	Musculoskeletal and connective tissue disorders	—
COUGH	Respiratory, thoracic and mediastinal disorders	—
DEPRESSION	Psychiatric disorders	—
DYSPNEA	Respiratory, thoracic and mediastinal disorders	—
EDEMA LIMBS	General disorders	—
GASTROINTESTINAL DISORDERS	Gastrointestinal disorders	—
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS	General disorders	—
HYPERTENSION	Vascular disorders	—
HYPOALBUMINEMIA	Metabolism and nutrition disorders	—

Most-reported serious reactions: FEBRILE NEUTROPENIA, ANAPHYLAXIS, COLITIS, DIARRHEA, ENDOCRINE DISORDERS, FEVER, GASTROINTESTINAL DISORDERS, NAUSEA.

Data from ClinicalTrials.gov NCT02375672 adverse events section.

Sponsor's own description

This is a multi-institutional, single arm, open-label, phase II study, including a safety run-in cohort. No randomization or blinding involved.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
   Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
2. Microsatellite instability in colorectal cancer: overview of its clinical significance and novel perspectives.
   Battaglin F, Naseem M, Lenz HJ, Salem ME. · · 2018 · cited 163× · PMID 30543589
3. Review of PD-1/PD-L1 Inhibitors in Metastatic dMMR/MSI-H Colorectal Cancer.
   Oliveira AF, Bretes L, Furtado I. · · 2019 · cited 152× · PMID 31139574 · DOI 10.3389/fonc.2019.00396
4. Immunotherapy for Colorectal Cancer.
   Boland PM, Ma WW. · · 2017 · cited 105× · PMID 28492495 · DOI 10.3390/cancers9050050
5. Immunogenomic Classification of Colorectal Cancer and Therapeutic Implications.
   Roelands J, Kuppen PJK, Vermeulen L, Maccalli C, et al · · 2017 · cited 103× · PMID 29064420 · DOI 10.3390/ijms18102229
6. Predictive biomarkers of colon cancer immunotherapy: Present and future.
   Hou W, Yi C, Zhu H. · · 2022 · cited 100× · PMID 36483562 · DOI 10.3389/fimmu.2022.1032314
7. The theory of tumor ecosystem.
   Chen X, Song E. · · 2022 · cited 93× · PMID 35642770 · DOI 10.1002/cac2.12316
8. PD-1 and PD-L1 inhibitors in cold colorectal cancer: challenges and strategies.
   Lin KX, Istl AC, Quan D, Skaro A, et al · · 2023 · cited 90× · PMID 37831146 · DOI 10.1007/s00262-023-03520-5