Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC) (MK-7690-046)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: Colorectal Neoplasms

Treatments: Biological: Pembrolizumab; Drug: Vicriviroc

Study type: Interventional

Funder types: Industry

Identifiers

NCT03631407

MK-7690-046 (Other Identifier)

7690-046

Details and patient eligibility

About

This trial will evaluate the safety and efficacy of vicriviroc (MK-7690) at 2 dose levels in combination with pembrolizumab (MK-3475) in participants with advanced/metastatic microsatellite stable (MSS) colorectal cancer (CRC).

Enrollment: 41 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a histologically proven locally advanced unresectable or metastatic CRC.
• Have locally confirmed MSS CRC.
• Have been previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan, and have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit.
• Have measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology.
• Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study intervention.
• Male participants must agree to use contraception and refrain from donating sperm for at least 120 days after the last dose of study intervention.
• Female participants must be not pregnant and not breastfeeding. Further, a female participant must either not be a woman of childbearing potential (WOCBP) or, if a WOCBP, agree to use contraception during the treatment period and for at least 120 days after the last dose of study intervention.
• Have adequate organ function.

Exclusion criteria

• Have a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Have known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Have severe hypersensitivity reaction to treatment with any monoclonal antibody or components of the study interventions.
• Have an active autoimmune disease requiring systemic treatment in the past 2 years, except vitiligo or resolved childhood asthma/atopy.
• Have a history of vasculitis.
• Have an active infection requiring systemic therapy.
• Have symptomatic ascites or pleural effusion.
• Have interstitial lung disease requiring oral or IV glucocorticoids.
• Have a history of pneumonitis (noninfectious) that required steroids, or has current pneumonitis.
• Have a known history of human immunodeficiency virus (HIV) infection.
• Have a known history of hepatitis B or known active hepatitis C virus infection.
• Have a known history of active tuberculosis (TB; Bacillus tuberculosis).
• Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, make administration of the study interventions hazardous, or make it difficult to monitor adverse events.
• Have a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with study requirements.
• Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention.
• Are a WOCBP who has a positive urine pregnancy test within 72 hours before randomization or treatment allocation.
• Have undergone major surgery and have not recovered adequately from any toxicity and/or complications from the intervention before starting study intervention.
• Have a seizure disorder requiring ongoing antiseizure therapy or with any condition that, in the judgment of the investigator, is likely to increase the risk of seizure (e.g., CNS malignancy or toxoplasmosis).
• Have known gastrointestinal (GI) disease such as esophageal, gastric, or duodenal ulceration or inflammatory bowel disease, or history of GI surgery.
• Are using any drug (therapeutic or recreational), or withdrawal thereof, that poses an increased risk of convulsions.
• Have had an allogeneic tissue/solid organ transplant.
• Have received prior therapy with vicriviroc or other CCR5 antagonist (e.g., maraviroc) or have received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent.
• Have been treated with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
• Have received prior systemic anticancer therapy, including investigational agents, or has used an investigational device within 28 days before the first dose of study intervention.
• Have received prior radiotherapy (not to target lesions) within 2 weeks of start of study intervention.
• Are expected to require any other form of antineoplastic therapy while on study.
• Have a diagnosis of immunodeficiency, is receiving chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or is taking any other form of immunosuppressive medication within 7 days before the first dose of the study intervention.
• Have received a live-virus vaccine within 30 days before the first dose of the study intervention.
• Are currently participating in or have participated in a study of an investigational agent, or have used an investigational device within 28 days before the first dose of study intervention.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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41 participants in 2 patient groups

Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)

Experimental group

Description:

Participants receive vicriviroc 150 mg tablets per os (PO) every day (QD) of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute intravenous (IV) infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Treatment:

Drug: Vicriviroc

Biological: Pembrolizumab

Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)

Experimental group

Description:

Participants receive vicriviroc 250 mg tablets PO QD of each 21-day cycle up to 35 cycles and pembrolizumab 200 mg as a 30-minute IV infusion on Day 1 of each 21 day cycle up to 35 cycles (cycle length: 21 days).

Treatment:

Drug: Vicriviroc

Biological: Pembrolizumab