Description:
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 MK-7684A, a co-formulated product of vibostolimab plus pembrolizumab,
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 MK-7684 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 MK-7684 plus pembrolizumab plus the investigator's
choice of platinum agent (carboplatin or cisplatin), and etoposide and efficacy of MK-7684A
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 MK-7684A is safe and tolerable when administered as a fixed
dose.
Title
- Brief Title: Study of MK-7684 Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001)
- Official Title: A Phase 1 Trial of MK-7684 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
Clinical Trial IDs
- ORG STUDY ID:
7684-001
- SECONDARY ID:
MK-7684-001
- NCT ID:
NCT02964013
Conditions
Interventions
Drug | Synonyms | Arms |
---|
MK-7684 | | MK-7684 |
pembrolizumab | KEYTRUDA® | MK-7684+pembrolizumab (pembro) |
pemetrexed | ALIMTA® | MK-7684+pembro+pemetrexed+carboplatin |
carboplatin | PARAPLATIN® | MK-7684+pembro+pemetrexed+carboplatin |
Purpose
This is a safety, efficacy, and pharmacokinetics study of 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 MK-7684 monotherapy or in combination
with pembrolizumab, pemetrexed, and carboplatin. Part A will also evaluate the anti-tumor
activity of MK-7684 in combination with pembrolizumab plus pemetrexed and carboplatin in
participants with non-small cell lung cancer (NSCLC) and MK-7684 (at two dose levels) in
combination with pembrolizumab in Japanese participants with gastric cancer. Part B will
evaluate the anti-tumor activity of MK-7684 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 MK-7684 in combination with pembrolizumab
in participants with programmed death 1 (PD-1) treatment naïve cancer using a 1:1 randomized
study design. The primary hypothesis is that MK-7684 administered as monotherapy or in
combination with pembrolizumab is safe when administered at the RPTD.
Trial Arms
Name | Type | Description | Interventions |
---|
MK-7684 | Experimental | During an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of MK-7684 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 MK-7684 on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | |
MK-7684+pembrolizumab (pembro) | Experimental | During an initial dose evaluation phase, participants will receive Dose A, B, C, D, E, or F of MK-7684 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 MK-7684 has been established. The RPTD will be established based on the number of DLTs at each dose level. Once the RPTD of MK-7684 is established, participants will continue receiving the RPTD of MK-7684 in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | |
Advanced solid tumor cohort | Experimental | Participants will receive the RPTD of MK-7684 monotherapy or the RPTD of MK-7684 in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | |
Randomized dose 1 comparison cohort | Experimental | Participants will be randomized to receive a fixed dose (Dose 1) of MK-7684 in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | |
Randomized dose 2 comparison cohort | Experimental | Participants will be randomized to receive a fixed dose (Dose 2) of MK-7684 in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | |
MK-7684+pembro+pemetrexed+carboplatin | Experimental | Participants will receive a fixed dose of MK-7684 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 MK-7684 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. | - MK-7684
- pembrolizumab
- pemetrexed
- carboplatin
|
MK-7684 Dose 1 Japanese cohort | Experimental | Japanese participants will be randomized to receive a fixed dose (Dose 1) of MK-7684 in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | |
MK-7684 Dose 2 Japanese cohort | Experimental | Japanese participants will be randomized to receive a fixed dose (Dose 2) of MK-7684 in combination with 200 mg pembrolizumab on Day 1 of each 21-day infusion cycle until the 35-cycle limit is reached. | |
Eligibility Criteria
Inclusion Criteria:
- 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 NSCLC added with Amendment 7: Must have a histologically
or cytologically confirmed diagnosis of stage IV (M1a or M1b per current AJCC
criteria, edition 8) non-squamous NSCLC
- For Parts A and B: Has histologically or cytologically confirmed metastatic solid
tumor
- Has measureable 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)
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
signing 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Number of Participants with Dose Limiting Toxicities (DLTs) |
Time Frame: | Up to 24 Months |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
Time Frame: | Up to 24 Months |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial 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
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