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)

NCT03631407 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 7690-046MK-7690-046
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 8

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

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)

Outcome Measures

Primary Outcomes (4)

• Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

  Objective response rate (ORR) was defined as the percentage of participants who experienced a 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) and was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by the investigator. ORR was estimated and analyzed using Clopper-Pearson interval.

  Up to ~32 months

• Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)

  DLTs were assessed during the first cycle (21 days) \& were defined as: Grade (Gr) 4 nonhematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, Gr 4 thrombocytopenia of any duration, Gr 3 thrombocytopenia associated with bleeding; nonhematologic adverse event (AE) ≥ Gr 3 (with exceptions); Gr 3 or 4 nonhematologic lab abnormality (if medical intervention was required, lead to hospitalization, or persisted for \>72 hours); Gr 3 or 4 febrile neutropenia; inability to receive ≥75% of the planned vicriviroc dose because of drug-related tolerability; drug-related toxicity that caused a \>2 week delay in Cycle 2 initiation; elevated aspartate aminotransferase or alanine aminotransferase lab value that is \>3× upper limit of normal (ULN) \& an elevated total bilirubin value \>2× ULN \& an alkaline phosphatase value \<2× ULN, in which no alternative reasons were found.

  Up to Day 21 of Cycle 1 (each cycle is 21 days)

• Number of Participants Who Experienced an Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed.

  Up to ~28 months

• Number of Participants Who Discontinued Study Treatment Due to an AE

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed

  Up to ~25 months

Secondary Outcomes (7)

• Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)

  Up to ~32 months

• Progression-Free Survival (PFS) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)

  Up to ~32 months

• PFS Based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)

  Up to ~32 months

• Overall Survival (OS)

  Up to ~32 months

• Plasma Area Under the Concentration Time-Curve From 0 to 8 Hours (AUC 0-8hrs) of Vicriviroc

  Pre-dose, 1, 2, 4, and 8 hours after vicriviroc administration on Cycle 1 (each cycle= 21-days) Day 1, Cycle 2 Day 1.

Study Arms (2)

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

EXPERIMENTAL

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).

Drug: Vicriviroc; Biological: Pembrolizumab

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

EXPERIMENTAL

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).

Drug: Vicriviroc; Biological: Pembrolizumab

Interventions

Vicriviroc DRUG

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

Also known as: MK-7690

Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg); Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)

Pembrolizumab BIOLOGICAL

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

Also known as: KEYTRUDA®, MK-3475

Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg); Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (8)

Honor Health ( Site 0103)

Scottsdale, Arizona, 85258, United States

Location

California Cancer Associates for Research & Excellence ( Site 0100)

Encinitas, California, 92024, United States

Location

California Cancer Associates for Research & Excellence ( Site 0102)

Fresno, California, 93720, United States

Location

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

Fort Myers, Florida, 33901-8101, United States

Location

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

Nashville, Tennessee, 37203, United States

Location

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

Temple, Texas, 76508, United States

Location

Cross Cancer Institute ( Site 0201)

Edmonton, Alberta, T6G 1Z2, Canada

Location

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

Montreal, Quebec, H1T 2M4, Canada

Location

Related Publications (1)

• 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.

  PMID: 38942693 RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body; Spinocerebellar Degenerations

Interventions

vicriviroc; pembrolizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2018
• First Posted: August 15, 2018
• Study Start: September 24, 2018
• Primary Completion: June 8, 2021
• Study Completion: June 8, 2021
• Last Updated: November 21, 2024
• Results First Posted: June 7, 2022

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share

Locations

CA (2); US (6)