Trial · NCT03374254
Safety and Efficacy of Pembrolizumab (MK-3475) Plus Binimetinib Alone or Pembrolizumab Plus Chemotherapy With or Without Binimetinib in Metastatic Colorectal Cancer (mCRC) Participants (MK-3475-651/KEYNOTE-651)
NCT03374254, Phase 1, Completed, Merck Sharp & Dohme LLC; results first posted 2024-10-15
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Safety and Efficacy of Pembrolizumab (MK-3475) Plus Binimetinib Alone or Pembrolizumab Plus Chemotherapy With or Without Binimetinib in Metastatic Colorectal Cancer (mCRC) Participants (MK-3475-651/KEYNOTE-651). Trials, record NCT03374254. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03374254
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
Safety and Efficacy of Pembrolizumab (MK-3475) Plus Binimetinib Alone or Pembrolizumab Plus Chemotherapy With or Without Binimetinib in Metastatic Colorectal Cancer (mCRC) Participants (MK-3475-651/KEYNOTE-651)
- NCT number
- NCT03374254
- Status
- Completed
- Phases
- Phase 1
- Enrollment
- 116 participants, actual
- Lead sponsor
- Merck Sharp & Dohme LLC
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Pembrolizumab, Binimetinib, Oxaliplatin, Leucovorin, 5-Fluorouracil [5-FU], Irinotecan
- First posted
- 2017-12-15
- Last updated
- 2024-11-21
- Results first posted
- 2024-10-15
Source ClinicalTrials.gov
Registered outcomes2
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Up to approximately first 28 days of treatment | The occurrence of any of the following toxicities during Part 1 of the study (the first 21 days for Cohort A, first 28 days for Cohorts B,C, D, \& E), if possibly, probably or definitely related to study treatment, was considered a DLT: Grade (Gr) 4 non hematologic toxicity, Gr 4 hematologic toxicity lasting \>7 days, Gr 3 thrombocytopenia, Any non-hematologic AE ≥Gr 3 in severity, Any Gr 3 or Gr 4 non-hematologic laboratory value, Febrile neutropenia Gr 3 or Gr 4, Any prolonged delay in initiating study therapy due to a treatment-related AE that started during the DLT period, Any treatment-related toxicity that causes the participant to discontinue treatment during the DLT period, Missing \>25% of binimetinib doses as a result of drug-related AE(s), Gr 5 toxicity, Cardiac disorders and vascular disorders, Eye disorders (Retinopathy or retinal detachment Gr ≥ 3). |
| Secondary | Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Up to Approximately 64 months | ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). The percentage of participants who experienced CR or PR is presented. Per Protocol, analysis was per cohort. |
Source ClinicalTrials.gov
Outcomes2
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Up to approximately first 28 days of treatment | Population based on all participants who received treatment and that were DLT Evaluable in Part 1 of study. These populations included all allocated participants in Part 1 who received at least 1 dose of study intervention according to the study intervention they received. | Percetange of Participants | NUMBER |
| SECONDARY | Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Up to Approximately 64 months | The analysis population consisted of all evaluable participants for each cohort with a baseline scan with measurable disease by investigator assessment who received at least 1 dose of study treatment. Per protocol, the populations were analyzed by cohort and treatment combination (irrespective of dose); therefore, data by individual dose were not analyzed. | Percentage of participants | NUMBER |
Source ClinicalTrials.gov
Results by group12
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg | 16.7 | 80% Confidence Interval 4.0 to 39.1 | Percetange of Participants | |
| Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg | 0.0 | 80% Confidence Interval 0.0 to 10.2 | Percetange of Participants | |
| Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Cohort B Part 1: Pembrolizumab + mFOLFOX7 | 0.0 | 80% Confidence Interval 0.0 to 9.6 | Percetange of Participants | |
| Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg | 27.3 | 80% Confidence Interval 13.4 to 45.0 | Percetange of Participants | |
| Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Cohort D Part 1: Pembrolizumab + FOLFIRI | 7.1 | 80% Confidence Interval 1.4 to 19.4 | Percetange of Participants | |
| Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg | 33.3 | 80% Confidence Interval 17.0 to 53.1 | Percetange of Participants | |
| Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT) | Cohort E Part 1: MK-3475 200 mg Q3W + FOLFIRI Q2W + Binimetinib 45 mg BID | 45.5 | 80% Confidence Interval 28.4 to 63.3 | Percetange of Participants | |
| Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Cohort A | 0.0 | 95% Confidence Interval 0.0 to 16.8 | Percentage of participants | |
| Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Cohort B | 61.3 | 95% Confidence Interval 42.2 to 78.2 | Percentage of participants | |
| Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) | Cohort C | 27.3 | 95% Confidence Interval 6.0 to 61.0 | Percentage of participants |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 results by groupParticipant flow36
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg | 6 | |
| Overall Study | STARTED | Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg | 16 | |
| Overall Study | STARTED | Cohort B Part 1: Pembrolizumab + mFOLFOX7 | 15 | |
| Overall Study | STARTED | Cohort B Part 2: Pembrolizumab + mFOLFOX7 | 16 | |
| Overall Study | STARTED | Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg | 11 | |
| Overall Study | STARTED | Cohort D Part 1: Pembrolizumab + FOLFIRI | 16 | |
| Overall Study | STARTED | Cohort D Part 2: Pembrolizumab + FOLFIRI | 16 | |
| Overall Study | STARTED | Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg | 9 | |
| Overall Study | STARTED | Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg | 11 | |
| Overall Study | Treated | Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg | 6 |
1 to 10 of 36Source ClinicalTrials.gov
See all 36 participant flowAdverse events4,806
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Anaemia | Blood and lymphatic system disorders | Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg | 1 | 6 | 1 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg | 2 | 14 | 2 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort B Part 1: Pembrolizumab + mFOLFOX7 | 4 | 15 | 7 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort B Part 2: Pembrolizumab + mFOLFOX | 5 | 16 | 9 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg | 3 | 11 | 4 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort D Part 1: Pembrolizumab + FOLFIRI | 9 | 16 | 21 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort D Part 2: Pembrolizumab + FOLFIRI | 3 | 16 | 3 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg | 5 | 9 | 7 |
| other | Anaemia | Blood and lymphatic system disorders | Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg | 4 | 11 | 5 |
| other | Febrile neutropenia | Blood and lymphatic system disorders | Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg | 0 | 6 | 0 |
1 to 10 of 4,806Source ClinicalTrials.gov
See all 4,806 adverse eventsAdverse event totals27
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg | 5 | 6 |
| Total, all-cause mortality | Cohort A Part 1: Pembrolizumab +Binimetinib 45 mg | 16 | 16 |
| Total, all-cause mortality | Cohort B Part 1: Pembrolizumab + mFOLFOX7 | 13 | 15 |
| Total, all-cause mortality | Cohort B Part 2: Pembrolizumab + mFOLFOX | 12 | 16 |
| Total, all-cause mortality | Cohort C Part 1: Pembrolizumab + mFOLFOX7 + Binimetinib 30 mg | 9 | 11 |
| Total, all-cause mortality | Cohort D Part 1: Pembrolizumab + FOLFIRI | 13 | 16 |
| Total, all-cause mortality | Cohort D Part 2: Pembrolizumab + FOLFIRI | 11 | 16 |
| Total, all-cause mortality | Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 30 mg | 6 | 9 |
| Total, all-cause mortality | Cohort E Part 1: Pembrolizumab + FOLFIRI + Binimetinib 45 mg | 7 | 11 |
| Total, other adverse events | Cohort A Part 1: Pembrolizumab +Binimetinib 30 mg | 6 | 6 |
1 to 10 of 27Source ClinicalTrials.gov
See all 27 adverse event totalsPapers2
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
Read this trial from software.
The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03374254
GET https://conductscience.org/api/trials/v1/NCT03374254/flow?page=2