The purpose of this study is to determine safety and tolerability and to establish a preliminary recommended Phase 2 dose (RP2D) for the following combinations: pembrolizumab plus binimetinib (Cohort A), pembrolizumab plus mFOLFOX7 (oxaliplatin 85 mg/m\^2; leucovorin \[calcium folinate\] 400 mg/m\^2; fluorouracil \[5-FU\] 2400 mg/m\^2) (Cohort B), pembrolizumab plus mFOLFOX7 and binimetinib (Cohort C), pembrolizumab plus FOLFIRI (irinotecan 180 mg/m\^2; leucovorin \[calcium folinate\]400 mg/m\^2; 5-FU 2400 mg/m\^2 over 46-48 hours) (Cohort D), and pembrolizumab plus FOLFIRI and binimetinib (Cohort E).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
116
200 mg Pembrolizumab solution for IV infusion Q3W
tablet orally BID at 30 or 45 mg depending upon DLT profile
85 mg/m\^2 as IV infusion. Administered Q2W as part of mFOLFOX7 cocktail. Dose may be de-escalated to 70 mg/m\^2 if the standard dose of mFOLFOX7 is deemed too toxic per mTPI, based upon occurrence of DLTs.
400 mg/m\^2 as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation.
2400 mg/m\^2 over 46-48 hours as IV infusion. Administered Q2W as part of mFOLFOX7 or FOLFIRI cocktail, depending upon allocation. Dose may be de-escalated to 2000 mg/m\^2 if the standard dose of mFOLFOX7 or FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
180 mg/m\^2 as IV infusion. Administered Q2W as part of FOLFIRI cocktail. Dose may be de-escalated to 150 mg/m\^2 if the standard dose of FOLFIRI is deemed too toxic per mTPI, based upon occurrence of DLTs.
City of Hope National Medical Center ( Site 0102)
Duarte, California, United States
Anschutz Medical Campus, Anschutz Cancer Pavilion ( Site 0106)
Aurora, Colorado, United States
Yale Cancer Center ( Site 0108)
New Haven, Connecticut, United States
Moffitt Cancer Center ( Site 0111)
Tampa, Florida, United States
University of Chicago ( Site 0105)
Chicago, Illinois, United States
Rutgers Cancer Institute of New Jersey ( Site 0107)
New Brunswick, New Jersey, United States
UPMC Cancer Center/Hillman Cancer Center ( Site 0113)
Pittsburgh, Pennsylvania, United States
Baylor Scott and White ( Site 0110)
Temple, Texas, United States
Seattle Cancer Care Alliance ( Site 0104)
Seattle, Washington, United States
Northwest Medical Specialties, PLLC ( Site 0101)
Tacoma, Washington, United States
...and 4 more locations
Percentage of Participants Who Experienced Dose-Limiting Toxicity (DLT)
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).
Time frame: Up to approximately first 28 days of treatment
Objective Response Rate (ORR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1)
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.
Time frame: Up to Approximately 64 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.