Phase 1
Completed N=474
Study of Vibostolimab Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001) ( KEYVIBE-001)
Neoplasms
Source: ClinicalTrials.gov NCT02964013 ↗
Enrolled (actual)
474
Serious AEs
33.9%
Results posted
Oct 2025
Primary outcomePrimary: Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months — 0; 0; 0; 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs) up to 24 Months |
0; 0; 0; 0; 1; 0 | — |
| PRIMARY Number of Participants Who Experienced At Least One Adverse Event (AE) |
67; 284; 24; 60; 10; 40 | — |
| PRIMARY Number of Participants Who Discontinued Study Treatment Due to an AE |
2; 30; 1; 4; 1; 3 | — |
| SECONDARY Overall Response Rate (ORR) in Participants in Vibostolimab Dose Escalation Phase Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
0.0; 7.1 | — |
| SECONDARY ORR in Participants With Programmed Death 1 (PD-1) Refractory Non-small Cell Lung Cancer (NSCLC) Per RECIST 1.1 |
2.4; 5.3 | — |
| SECONDARY ORR in Participants With PD-1 Naive NSCLC Per RECIST 1.1 |
24.4 | — |
| SECONDARY ORR in Participants With Extensive-stage Small Cell Lung Cancer (ES-SCLC) Per RECIST 1.1 |
75.0 | — |
| SECONDARY ORR in Participants With PD-1 Naive Ovarian Cancer Per RECIST 1.1 |
9.5; 7.5 | — |
| SECONDARY ORR in Participants With PD-1 Naive Cervical Cancer Per RECIST 1.1 |
14.6; 23.1 | — |
| SECONDARY Area Under the Curve From Time 0 to 21 Days Postdose (AUC 0-21 Days) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab |
5.42; 8.19; 12.2; 12.0; 12.4; NA | — |
| SECONDARY AUC 0-21 Days of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments |
339; 354; 431; 317; 476; 572 | — |
| SECONDARY AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab |
760; 749; NA; 516; 922; 504 | — |
| SECONDARY AUC 0-21 Days of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments |
516; 546; 539; 641; 887; 946 | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab |
1.52; 1.67; 7.23; 2.09; 7.57; NA | — |
| SECONDARY Cmax of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments |
62.6; 64.4; 59.9; 60.1; 59.6; 82.7 | — |
| SECONDARY Cmax of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab |
89.3; 86.4; NA; 58.4; 95.0; 90.5 | — |
| SECONDARY Cmax of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments |
76.1; 66.4; 71.6; 64.4; 93.9; 73.2 | — |
| SECONDARY Trough Concentration (Ctrough) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Ctrough of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments |
3.82; 5.05; 8.01; 2.50; 4.16; 10.7 | — |
| SECONDARY Ctrough of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab |
19.8; 20.6; NA; 10.4; 28.0; 12.3 | — |
| SECONDARY Ctrough of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments |
12.1; 13.2; 12.5; 10.9; 23.3; 24.7 | — |
| SECONDARY Half Life (t1/2)) of Plasma Vibostolimab Following Treatment With Increasing Amounts of Vibostolimab Monotherapy or Vibostolimab With 200 mg Pembrolizumab |
3.82; NA; 4.04; NA; 3.54; NA | — |
| SECONDARY t1/2 of Plasma Vibostolimab Following Treatment With 200 mg Vibostolimab Combined With Various Other Treatments |
7.38; 9.09; 5.38; NA; 10.5; NA | — |
| SECONDARY t1/2 of Plasma Pembrolizumab Following Treatment With Increasing Amounts of Vibostolimab With 200 mg Pembrolizumab |
19.6; 20.1; NA; 8.84; 18.6; 13.1 | — |
| SECONDARY t1/2 of Plasma Pembrolizumab Following Treatment With 200 mg Vibostolimab and 200 mg Pembrolizumab Combined With Various Other Treatments |
11.2; 12.4; 16.6; NA; 14.3; NA | — |
| SECONDARY Number of Participants Experiencing a Dose-Limiting Toxicity (DLT) at the End of Cycle 1 |
0; 0; 0; 0; 1; 0 | — |
| SECONDARY Rate of Progression Free Survival (PFS) Per RECIST 1.1 at 6 Months |
35.0 | — |
Eligibility 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
Data sourced from ClinicalTrials.gov (NCT02964013). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.