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Study of Vibostolimab Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02964013
Recruitment Status : Recruiting
First Posted : November 15, 2016
Last Update Posted : November 29, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a safety, efficacy, and pharmacokinetics (PK) study of vibostolimab (MK-7684) as monotherapy and in combination with pembrolizumab (MK-3475) or pembrolizumab plus pemetrexed and carboplatin in adults with metastatic solid tumors for which there is no available therapy that is expected to convey clinical benefit. Part A of this study is a dose escalation and confirmation phase to estimate the recommended Phase 2 dose (RPTD) for vibostolimab monotherapy or in combination with pembrolizumab, pemetrexed, and carboplatin. Part A will also evaluate the anti-tumor activity of vibostolimab in combination with pembrolizumab plus pemetrexed and carboplatin in participants with non-small cell lung cancer (NSCLC) and vibostolimab (at two dose levels) in combination with pembrolizumab in Japanese participants with gastric cancer. Part B will evaluate the anti-tumor activity of vibostolimab at the RPTD when used as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors in a non-randomized study design. Part B will also evaluate 2 doses of vibostolimab in combination with pembrolizumab in participants with programmed death 1 (PD-1) treatment naïve cancer using a 1:1 randomized study design. Part B is expanded with Amendment 11 to include an additional arm that will compare the safety and PK of a fixed dose of pembrolizumab/vibostolimab coformulation (MK-7684A) to vibostolimab in combination with pembrolizumab administered as separate intravenous infusions. Part A is expanded with Amendment 12 to include an additional arm that will compare the safety and PK of vibostolimab plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide. Part B is expanded with Amendment 12 to include evaluation of efficacy of vibostolimab plus pembrolizumab plus the investigator's choice of platinum agent (carboplatin or cisplatin), and etoposide and efficacy of pembrolizumab/vibostolimab coformulation in participants from mainland China. The primary hypotheses are that vibostolimab administered as monotherapy or in combination with pembrolizumab is safe and tolerable when administered at the RPTD and that pembrolizumab/vibostolimab coformulation is safe and tolerable when administered as a fixed dose.

Condition or disease Intervention/treatment Phase
Neoplasms Biological: vibostolimab Biological: pembrolizumab Drug: pemetrexed Drug: carboplatin Biological: pembrolizumab/vibostolimab coformulation Drug: cisplatin Drug: etoposide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 492 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Trial of MK-7684 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
Actual Study Start Date : December 13, 2016
Estimated Primary Completion Date : January 24, 2025
Estimated Study Completion Date : January 24, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: vibostolimab
During an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of vibostolimab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the RPTD has been established. The RPTD will be established based on the number of dose limiting toxicities (DLTs) at each dose level. Once the RPTD is established, participants will continue receiving the RPTD of vibostolimab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Experimental: vibostolimab + pembrolizumab
During an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle (for a maximum of 35 cycles) until the RPTD of vibostolimab has been established. The RPTD will be established based on the number of DLTs at each dose level. Once the RPTD of vibostolimab is established, participants will continue receiving the RPTD of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Experimental: Advanced solid tumor cohort
Participants will receive the RPTD of vibostolimab monotherapy or the RPTD of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Experimental: Randomized dose 1 comparison cohort
Participants will be randomized to receive a fixed dose (Dose 1) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Experimental: Randomized dose 2 comparison cohort
Participants will be randomized to receive a fixed dose (Dose 2) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Experimental: vibostolimab +pembrolizumab+pemetrexed+carboplatin
Participants will receive a fixed dose of vibostolimab in combination with 200 mg pembrolizumab, 500 mg/m^2 pemetrexed, and Area Under Curve (AUC) 5 mg/mL/min carboplatin on Day 1 of each 21-day infusion cycle for up to 4 cycles followed by maintenance therapy with a fixed dose of vibostolimab in combination with 200 mg pembrolizumab and 500 mg/m^2 pemetrexed on Day 1 of each 21-day infusion cycle for up to an additional 31 cycles.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Drug: pemetrexed
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: ALIMTA®

Drug: carboplatin
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4
Other Name: PARAPLATIN®

Experimental: vibostolimab Dose 1 Japanese cohort
Japanese participants will be randomized to receive a fixed dose (Dose 1) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Experimental: vibostolimab Dose 2 Japanese cohort
Japanese participants will be randomized to receive a fixed dose (Dose 2) of vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Experimental: pembrolizumab/vibostolimab coformulation
Participants will receive a fixed dose of pembrolizumab/vibostolimab coformulation, consisting of 200 mg of pembrolizumab + 200 mg vibostolimab, on Day 1 of each 21-day infusion cycle for up to 35 cycles.
Biological: pembrolizumab/vibostolimab coformulation
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684A

Experimental: vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide
Participants will receive 200 mg vibostolimab in combination with 200 mg pembrolizumab, plus the investigator's choice of Area Under Curve (AUC) 5 mg/mL/min carboplatin OR 75 mg/m^2 cisplatin on Day 1 of each 21-day cycle plus 100 mg/m^2/day etoposide on Days 1-3 of each 21-day cycle for up to 4 cycles. Maintenance therapy with 200 mg vibostolimab in combination with 200 mg pembrolizumab on Day 1 of each 21-day cycle will continue for up to an additional 31 cycles. A participant will be allowed to switch from cisplatin to carboplatin in the event of an adverse event (AE), ineligibility for further cisplatin therapy, and/or the investigator considers switching to carboplatin to be in the best interest of the participant.
Biological: vibostolimab
Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684

Biological: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Names:
  • KEYTRUDA®
  • MK-3475

Drug: carboplatin
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4
Other Name: PARAPLATIN®

Drug: cisplatin
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4
Other Name: PLATINOL-AQ®

Drug: etoposide
Administered as an IV infusion on Days 1-3 of 21-day infusion Cycles 1-4
Other Name: ETOPOPHOS®

Experimental: pembrolizumab/vibostolimab coformulation China cohort
Participants from mainland China will receive a fixed dose of pembrolizumab/vibostolimab coformulation, consisting of 200 mg of pembrolizumab + 200 mg vibostolimab, on Day 1 of each 21-day infusion cycle for up to 35 cycles.
Biological: pembrolizumab/vibostolimab coformulation
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35
Other Name: MK-7684A




Primary Outcome Measures :
  1. Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 24 Months ]
  2. Number of Participants Who Experienced At Least One Adverse Event (AE) [ Time Frame: Up to 27 Months ]
  3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [ Time Frame: Up to 24 Months ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to 24 Months ]
  2. Area Under the Concentration-Time Curve [ Time Frame: Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days. ]
  3. Maximum Plasma Concentration (Cmax) [ Time Frame: Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days. ]
  4. Trough Concentration (CTrough) [ Time Frame: Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days. ]
  5. Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) [ Time Frame: At the end of Cycle 1 (cycle length is 21 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Part A participants enrolled prior to Amendment 7, must have a histologically or cytologically confirmed metastatic solid tumor for which there is no available therapy that is expected to convey clinical benefit
  • For Part A Japanese cohort added with Amendment 7: Must reside in Japan and be of Japanese descent and have adenocarcinoma of the stomach and/or gastric-esophageal junction (GEJ) that is considered inoperable and that has received, and progressed on, at least 1 prior chemotherapy regimen or human epidermal growth factor receptor 2 (HER2)/neu-targeted approved therapy (if HER2/neu-positive). In both cases, participants may be untreated or could have received and progressed on 1 prior regimen, but must not have received prior anti-PD-1/PD-L1 therapy
  • For Part A participants with non-small cell lung cancer (NSCLC) added with Amendment 7: Must have a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b per current American Joint Committee on Cancer criteria, edition 8) non-squamous NSCLC
  • For Part B China participants added with Amendment 12. Must have a histologically or cytologically confirmed metastatic solid tumor for which no more than 2 prior lines of therapy were administered and there is no available therapy that is expected to convey clinical benefit AND be Chinese from mainland China
  • For Parts A and B: Has histologically or cytologically confirmed metastatic solid tumor
  • Has measurable disease by Response Evaluation Criteria In Solid Tumors (RECIST)
  • Has an Eastern Cooperative Oncology Group performance status of 0 to 1
  • Females must not be pregnant
  • Women of childbearing potential and male participants must agree to use adequate contraception for the course of the study
  • Has provided a tumor tissue sample (archival or newly obtained core or excisional biopsy of a tumor lesion)
  • For Chinese participants enrolled as part of Amendment 12. No tumor tissue samples will be collected

Exclusion Criteria:

  • Has had chemotherapy, radiation, biological cancer therapy or major surgery within 4 weeks prior to the first dose of study treatment
  • Has not recovered to Common Toxicity Criteria for Adverse Events Grade 1 or better from the adverse events due to cancer therapeutics administered more than 4 weeks prior to the first dose of study treatment
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
  • Has received previous treatment with another agent targeting the T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif (TIGIT) receptor
  • Has received previous treatment with an immunomodulatory agent (e.g., anti-programmed cell death 1, anti-programmed cell death ligand 1 or cytotoxic T-lymphocyte-associated protein 4) and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event
  • Is expected to require any other form of antineoplastic therapy while participating in the trial
  • Is on chronic systemic steroid therapy in excess of replacement doses or on any other form of immunosuppressive medication
  • Has a history of a previous additional malignancy unless potentially curative treatment has been completed with no evidence of malignancy for 5 years
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease
  • Has an active infection requiring systemic treatment
  • Has interstitial lung disease
  • Has active or past history of (non-infectious) pneumonitis requiring steroids
  • Has symptomatic ascites or pleural effusion
  • Has previously had a hematopoetic stem cell transplant or solid organ transplant
  • Is known to be human immunodeficiency virus (HIV) positive and/or known to have active chronic or acute Hepatitis B or Hepatitis C
  • Has a known psychiatric and/or substance abuse disorder that would make it difficult for the participant to cooperate with the requirements of the trial
  • Is a regular user (including recreational use) of any illicit drugs at the time of providing documented informed consent, or has a recent history (within the last year) of substance abuse
  • Has received a live virus vaccine within 30 days prior to the first dose of study treatment
  • Has had hormonal cancer therapy (e.g., tamoxifen, leuprolide). within 4 weeks prior to the first dose of study treatment
  • For Part A participants with NSCLC added with Amendment 7: Is unable to interrupt aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) other than an aspirin dose ≤1.3 gram per day for a 5-day period (8-day period for long-acting agents, such as piroxicam)
  • For Part A participants with NSCLC added with Amendment 7: Is unable or unwilling to take folic acid or Vitamin B12 supplementation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02964013


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839

Locations
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United States, Arizona
Call for Information (Investigational Site 0013) Recruiting
Gilbert, Arizona, United States, 85234
United States, Colorado
Call for Information (Investigational Site 0006) Recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Call for Information (Investigational Site 0003) Recruiting
New Haven, Connecticut, United States, 06511
United States, Michigan
Call for Information (Investigational Site 0009) Recruiting
Detroit, Michigan, United States, 48201
United States, North Carolina
Call for Information (Investigational Site 0011) Recruiting
Charlotte, North Carolina, United States, 28204
United States, Pennsylvania
Call for Information (Investigational Site 0010) Recruiting
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Call for Information (Investigational Site 0004) Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Call for Information (Investigational Site 0001) Recruiting
San Antonio, Texas, United States, 78229
Australia
Merck Sharp & Dohme Recruiting
North Ryde, Australia
Contact: Australian Medical Information Centre    61 2 8988 8428      
China
Merck Sharp & Dohme (China) Ltd. Recruiting
Beijing, China
Contact: Zaiqi Wang    +86 10 5860 9288      
Israel
Merck Sharp & Dohme Co. Ltd. Recruiting
Hod Hasharon, Israel
Contact: Gally Teper    972-9-9533310      
Korea, Republic of
MSD Korea LTD Recruiting
Seoul, Korea, Republic of, 4130
Contact: Jongho Ahn    82-2-331-2000 2015      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02964013    
Other Study ID Numbers: 7684-001
MK-7684-001 ( Other Identifier: Merck )
194809 ( Registry Identifier: JAPAC-CTI )
First Posted: November 15, 2016    Key Record Dates
Last Update Posted: November 29, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death Receptor 1 (PD-1)
Programmed Cell Death Receptor Ligand 1 (PD-L1)
Programmed Cell Death Receptor Ligand 2 (PD-L2)
PD-1
PDL1
PD-L1
PD-L2
Additional relevant MeSH terms:
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Carboplatin
Pembrolizumab
Etoposide
Pemetrexed
Antineoplastic Agents
Antineoplastic Agents, Immunological
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors