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Colorectal NeoplasmsPhase 2NCT03631407

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)

A Phase 2 study testing Vicriviroc and Pembrolizumab in people with Colorectal Neoplasms, run by Merck Sharp & Dohme LLC at 8 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Colorectal Neoplasms
What is being tested?
Vicriviroc and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
8 sitesin 2 countries
Study dates
24 Sep 2018to 8 Jun 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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 locations and contacts

8 sites in 2 countries.

8 sites in 2 countries

United States6 sites

  • California Cancer Associates for Research & Excellence ( Site 0100)

    Encinitas, California, 92024

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

    Fort Myers, Florida, 33901-8101

  • California Cancer Associates for Research & Excellence ( Site 0102)

    Fresno, California, 93720

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

    Nashville, Tennessee, 37203

  • Honor Health ( Site 0103)

    Scottsdale, Arizona, 85258

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

    Temple, Texas, 76508

Other trials in United States

Canada2 sites

  • Cross Cancer Institute ( Site 0201)

    Edmonton, Alberta, T6G 1Z2

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

    Montreal, Quebec, H1T 2M4

Other trials in Canada

About this study

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)

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).

Being tested
Vicriviroc, Pembrolizumab
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)
Medical subject headings
Colorectal Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body, Spinocerebellar Degenerations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VicrivirocDrug

    Also called MK-7690

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

  • PembrolizumabBiological

    Also called KEYTRUDA®, MK-3475

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

Study groups in NCT03631407
Study groupRoleWhat they receive
Vicriviroc QD at Dose Level 1 (150 mg) + Pembrolizumab (200 mg)ExperimentalParticipants 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).
Receives: Drug: Vicriviroc; Biological: Pembrolizumab
Vicriviroc QD at Dose Level 2 (250 mg) + Pembrolizumab (200 mg)ExperimentalParticipants 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).
Receives: Drug: Vicriviroc; Biological: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to ~32 months

  2. 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.

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

  3. 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.

    Measured: Up to ~28 months

  4. 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

    Measured: Up to ~25 months

Secondary outcomes (7)

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

    An objective response rate was defined as the percentage of participants who experienced an immune-based complete response (iCR: disappearance of all target lesions) or immune-based partial response (iPR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced an iCR or iPR using immune-based therapeutics Response Evaluation Criteria in Solid Tumors (iRECIST) per investigator was presented. ORR was estimated and analyzed using Clopper-Pearson interval.

    Measured: Up to ~32 months

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

    PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by investigator per RECIST 1.1 or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

    Measured: Up to ~32 months

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

    PFS was defined as the time from the first dose of study treatment to the date of the first documentation of disease progression, as determined by investigator per modified iRECIST or death due to any cause (whichever occurred first). Disease progression was defined as at least 20 percent (%) increase (including an absolute increase of at least 5 millimeter [mm]) in the sum of diameter of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. PFS was estimated and analyzed using Kaplan-Meier method.

    Measured: Up to ~32 months

  4. Overall Survival (OS)

    OS is defined as the time from the first dose of study treatment until death from any cause.

    Measured: Up to ~32 months

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

    Plasma vicriviroc concentration was quantified for each arm to determine AUC 0-8hrs, defined as the area under the concentration vs. time curve for vicriviroc from 0 to 8 hours.

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

  6. Maximum Observed Plasma Concentration (Cmax) of Vicriviroc

    Plasma vicriviroc concentration was quantified for each arm to determine Cmax, defined as the maximum observed concentration of vicriviroc in plasma.

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

  7. Trough Plasma Concentration (Ctrough) of Vicriviroc

    Plasma vicriviroc concentration was quantified for each arm to determine Ctrough, defined as the minimum plasma concentration of vicriviroc observed after administration and just before the subsequent dose.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2018
  2. Study start24 Sep 2018
  3. Primary completion8 Jun 2021
  4. Study completion8 Jun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03631407
Sponsor's protocol ID
7690-046
Other IDs
MK-7690-046
Status last verified
Nov 2024
First submitted
9 Aug 2018
Last updated
21 Nov 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 38942693

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vicriviroc and Pembrolizumab in people with Colorectal Neoplasms, run by Merck Sharp & Dohme LLC at 8 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1) (time frame: Up to ~32 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03631407, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Nov 2024.

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