Clinical trial NCT03631407: 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)
Official title: A Phase 2 Trial to Evaluate the Safety and Efficacy of Vicriviroc (MK-7690) in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic Microsatellite Stable (MSS) Colorectal Cancer (CRC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Keywords: programmed cell death 1 (PD-1, PD1 )
programmed cell death ligand 1 (PD-L1, PDL1)
microsatellite stable (MSS) colorectal cancer (CRC)
chemokine receptor type 5 (CCR5)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
timeFrame: Up to ~32 months
measure: Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
timeFrame: Up to Day 21 of Cycle 1 (each cycle is 21 days)
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to ~28 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to ~25 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)
timeFrame: Up to ~32 months
measure: Progression-Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
timeFrame: Up to ~32 months
measure: PFS Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)
timeFrame: Up to ~32 months
measure: Overall Survival (OS)
timeFrame: Up to ~32 months
measure: Plasma Area Under the Concentration Time-Curve From 0 to 8 Hours (AUC 0-8hrs) of Vicriviroc
timeFrame: Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.
measure: Maximum Observed Plasma Concentration (Cmax) of Vicriviroc
timeFrame: Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.
measure: Trough Plasma Concentration (Ctrough) of Vicriviroc
timeFrame: Pre-dose, and 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1; Cycle 3 Day 21.
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health ( Site 0103)
state: Arizona
city: Encinitas
country: United States
facility: California Cancer Associates for Research & Excellence ( Site 0100)
state: California
city: Fresno
country: United States
facility: California Cancer Associates for Research & Excellence ( Site 0102)
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists (South Region) - Research Office ( Site 7001)
state: Florida
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000)
state: Tennessee
city: Temple
country: United States
facility: Baylor Scott & White Medical Center - Temple ( Site 0104)
state: Texas
city: Edmonton
country: Canada
facility: Cross Cancer Institute ( Site 0201)
state: Alberta
city: Montreal
country: Canada
facility: CIUSSS de l Est de L Ile de Montreal - Hopital Maisonneuve-Rosemont ( Site 0204)
state: Quebec
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.