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

NCT02964013 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: 7684-001MK-7684-001194809KEYVIBE-001
• Study Type: interventional
• Target: 474
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months

  A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE4.0).

  Up to 24 Months

• Number of Participants Who Experienced At Least One Adverse Event (AE)

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

  Up to 28 Months

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

  An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event.

  Up to 24 Months

Secondary Outcomes (24)

• Overall Response Rate (ORR) in Participants in Vibostolimab Dose Escalation Phase Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to 24 Months

• ORR in Participants With Programmed Death 1 (PD-1) Refractory Non-small Cell Lung Cancer (NSCLC) Per RECIST 1.1

  Up to 24 Months

• ORR in Participants With PD-1 Naive NSCLC Per RECIST 1.1

  Up to 24 Months

• ORR in Participants With Extensive-stage Small Cell Lung Cancer (ES-SCLC) Per RECIST 1.1

  Up to 24 Months

• ORR in Participants With PD-1 Naive Ovarian Cancer Per RECIST 1.1

  Up to 24 Months

Study Arms (11)

vibostolimab

EXPERIMENTAL

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

vibostolimab + pembrolizumab

EXPERIMENTAL

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; Biological: pembrolizumab

Advanced solid tumor cohort

EXPERIMENTAL

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; Biological: pembrolizumab

Randomized dose 1 comparison cohort

EXPERIMENTAL

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; Biological: pembrolizumab

Randomized dose 2 comparison cohort

EXPERIMENTAL

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; Biological: pembrolizumab

vibostolimab +pembrolizumab+pemetrexed+carboplatin

EXPERIMENTAL

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; Biological: pembrolizumab; Drug: pemetrexed; Drug: carboplatin

vibostolimab Dose 1 Japanese cohort

EXPERIMENTAL

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; Biological: pembrolizumab

vibostolimab Dose 2 Japanese cohort

EXPERIMENTAL

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; Biological: pembrolizumab

pembrolizumab/vibostolimab coformulation

EXPERIMENTAL

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

vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide

EXPERIMENTAL

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; Biological: pembrolizumab; Drug: carboplatin; Drug: cisplatin; Drug: etoposide

pembrolizumab/vibostolimab coformulation China cohort

EXPERIMENTAL

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

Interventions

vibostolimab BIOLOGICAL

Administered as an intravenous (IV) infusion on Day 1 of 21-day infusion Cycles 1-35

Also known as: MK-7684

Advanced solid tumor cohort; Randomized dose 1 comparison cohort; Randomized dose 2 comparison cohort; vibostolimab; vibostolimab + pembrolizumab; vibostolimab +pembrolizumab+pemetrexed+carboplatin; vibostolimab Dose 1 Japanese cohort; vibostolimab Dose 2 Japanese cohort; vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide

pembrolizumab BIOLOGICAL

Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35

Also known as: KEYTRUDA®, MK-3475

Advanced solid tumor cohort; Randomized dose 1 comparison cohort; Randomized dose 2 comparison cohort; vibostolimab + pembrolizumab; vibostolimab +pembrolizumab+pemetrexed+carboplatin; vibostolimab Dose 1 Japanese cohort; vibostolimab Dose 2 Japanese cohort; vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide

pemetrexed DRUG

Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35

Also known as: ALIMTA®

vibostolimab +pembrolizumab+pemetrexed+carboplatin

carboplatin DRUG

Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4

Also known as: PARAPLATIN®

vibostolimab +pembrolizumab+pemetrexed+carboplatin; vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide

pembrolizumab/vibostolimab coformulation BIOLOGICAL

Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35

Also known as: MK-7684A

pembrolizumab/vibostolimab coformulation; pembrolizumab/vibostolimab coformulation China cohort

cisplatin DRUG

Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4

Also known as: PLATINOL-AQ®

vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide

etoposide DRUG

Administered as an IV infusion on Days 1-3 of 21-day infusion Cycles 1-4

Also known as: ETOPOPHOS®

vibostolimab+pembrolizumab+carboplatin OR cisplatin+etoposide

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Niu J, Maurice-Dror C, Lee DH, Kim DW, Nagrial A, Voskoboynik M, Chung HC, Mileham K, Vaishampayan U, Rasco D, Golan T, Bauer TM, Jimeno A, Chung V, Chartash E, Lala M, Chen Q, Healy JA, Ahn MJ. First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer☆. Ann Oncol. 2022 Feb;33(2):169-180. doi: 10.1016/j.annonc.2021.11.002. Epub 2021 Nov 18.

  PMID: 34800678 RESULT

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Pemetrexed; Carboplatin; Cisplatin; Etoposide; etoposide phosphate

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Clinical Trials Disclosure
• 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 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2016
• First Posted: November 15, 2016
• Study Start: December 13, 2016
• Primary Completion: July 24, 2024
• Study Completion: July 24, 2024
• Last Updated: October 14, 2025
• Results First Posted: October 14, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share