Clinical Trials /

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

Description:

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).

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 7690-046
  • SECONDARY ID: MK-7690-046
  • NCT ID: NCT03631407

Conditions

  • Colorectal Neoplasms

Interventions

DrugSynonymsArms
VicrivirocVicriviroc QD at Dose Level 1 + Pembrolizumab
PembrolizumabKEYTRUDA®, MK-3475Vicriviroc QD at Dose Level 1 + Pembrolizumab

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
Vicriviroc QD at Dose Level 1 + PembrolizumabExperimentalParticipants vicriviroc (dosed orally; once daily [QD]) at dose level 1 in combination with 200 mg pembrolizumab (intravenous [IV] infusion; every 3 weeks [Q3W]) for up to 35 cycles (cycle length: 3 weeks).
  • Vicriviroc
Vicriviroc QD at Dose Level 2 + PembrolizumabExperimentalParticipants receive vicriviroc (dosed orally; QD) at dose level 2 in combination with 200 mg pembrolizumab (IV infusion; Q3W) for up to 35 cycles (cycle length: 3 weeks).
  • Vicriviroc

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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1)
Time Frame:Up to 2 years
Safety Issue:
Description:ORR is defined as the percentage of participants who achieve a confirmed complete response ([CR]; disappearance of all target lesions) or partial response ([PR]: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 criteria.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR) based on Modified Response Evaluation Criteria in Solid Tumors 1.1 for Immune-based Therapeutics (iRECIST)
Time Frame:Up to 2 years
Safety Issue:
Description:A modification of RECIST1.1, iRECIST is adapted to account for the unique tumor response seen with immunotherapeutic drugs. Following initial identification of progressive disease (PD) based on RECIST 1.1, participants who are clinically stable can remain on treatment until PD is confirmed or disconfirmed by iRECIST. For participants where PD is disconfirmed by iRECIST, ORR will be determined, defined as the percentage of participants who achieve a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions).
Measure:Progression-Free Survival (PFS)
Time Frame:Up to 2 years
Safety Issue:
Description:PFS is the time from the first dose of study treatment to the first documented disease progression (per RECIST 1.1 criteria) or death due to any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to 2 years
Safety Issue:
Description:OS is defined as the time from the first dose of study treatment until death from any cause.
Measure:Area Under the Concentration vs Time Curve (AUC) of Vicriviroc in Plasma
Time Frame:At designated time points (up to 6 weeks post-dose)
Safety Issue:
Description:Plasma vicriviroc concentration will be quantified for each arm to determine AUC, defined as the area under the concentration vs. time curve for vicriviroc.
Measure:Maximum Observed Plasma Concentration (Cmax) of Vicriviroc
Time Frame:At designated time points (up to 6 weeks post-dose)
Safety Issue:
Description:Plasma vicriviroc concentration will be quantified for each arm to determine Cmax, defined as the maximum observed concentration of vicriviroc in plasma.
Measure:Trough Plasma Concentration (Ctrough) of Vicriviroc
Time Frame:At designated time points (up to 2 years post-dose)
Safety Issue:
Description:Plasma vicriviroc concentration will be quantified for each arm to determine Ctrough, defined as the minimum plasma concentration of vicriviroc observed after administration and just before the subsequent dose.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial 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)

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