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)

NCT ID: NCT03631407

Last Updated: 2024-11-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-24
• Study Completion Date: 2021-06-08

Brief Summary

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).

Conditions

Colorectal Neoplasms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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).

Group Type: EXPERIMENTAL

Vicriviroc

Intervention Type: DRUG

Vicriviroc tablets administered orally, QD at dose level 1 or 2.

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab administered by IV infusion at 200 mg every 3 weeks (Q3W), given on cycle day 1.

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

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).

Group Type: EXPERIMENTAL

Vicriviroc

Intervention Type: DRUG

Vicriviroc tablets administered orally, QD at dose level 1 or 2.

Pembrolizumab

Intervention Type: BIOLOGICAL

Pembrolizumab administered by IV infusion at 200 mg every 3 weeks (Q3W), given on cycle day 1.

Interventions

Vicriviroc

Vicriviroc tablets administered orally, QD at dose level 1 or 2.

Intervention Type: DRUG

Pembrolizumab

Pembrolizumab administered by IV infusion at 200 mg every 3 weeks (Q3W), given on cycle day 1.

Intervention Type: BIOLOGICAL

Other Intervention Names

MK-7690; KEYTRUDA®; MK-3475

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

Honor Health ( Site 0103)

Scottsdale, Arizona, United States

California Cancer Associates for Research & Excellence ( Site 0100)

Encinitas, California, United States

California Cancer Associates for Research & Excellence ( Site 0102)

Fresno, California, United States

Florida Cancer Specialists (South Region) - Research Office ( Site 7001)

Fort Myers, Florida, United States

Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000)

Nashville, Tennessee, United States

Baylor Scott & White Medical Center - Temple ( Site 0104)

Temple, Texas, United States

Cross Cancer Institute ( Site 0201)

Edmonton, Alberta, Canada

CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0204)

Montreal, Quebec, Canada

Countries

United States; Canada

References

Bessudo A, Haseeb AM, Reeves JA, Zhu X, Wong L, Giranda V, Suttner L, Liu F, Chatterjee M, Sharma S. Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab in Patients With Advanced or Metastatic Microsatellite Stable Colorectal Cancer. Clin Colorectal Cancer. 2024 Sep;23(3):285-294. doi: 10.1016/j.clcc.2024.05.003. Epub 2024 May 13.

Reference Type: RESULT

PMID: 38942693 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MK-7690-046

Identifier Type: OTHER

Identifier Source: secondary_id

7690-046

Identifier Type: -

Identifier Source: org_study_id