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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02964013




Registration number
NCT02964013
Ethics application status
Date submitted
11/11/2016
Date registered
15/11/2016
Date last updated
25/04/2022

Titles & IDs
Public title
Study of Vibostolimab Alone and in Combination With Pembrolizumab in Advanced Solid Tumors (MK-7684-001) ( KEYVIBE-001)
Scientific title
A Phase 1 Trial of MK-7684 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors
Secondary ID [1] 0 0
MK-7684-001
Secondary ID [2] 0 0
7684-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neoplasms 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - vibostolimab
Other interventions - pembrolizumab
Treatment: Drugs - pemetrexed
Treatment: Drugs - carboplatin
Other interventions - pembrolizumab/vibostolimab coformulation
Treatment: Drugs - cisplatin
Treatment: Drugs - etoposide

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.


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

Other interventions: pembrolizumab
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35

Treatment: Drugs: pemetrexed
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35

Treatment: Drugs: carboplatin
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4

Other interventions: pembrolizumab/vibostolimab coformulation
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-35

Treatment: Drugs: cisplatin
Administered as an IV infusion on Day 1 of 21-day infusion Cycles 1-4

Treatment: Drugs: etoposide
Administered as an IV infusion on Days 1-3 of 21-day infusion Cycles 1-4
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants with Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 24 Months
Primary outcome [2] 0 0
Number of Participants Who Experienced At Least One Adverse Event (AE)
Timepoint [2] 0 0
Up to 27 Months
Primary outcome [3] 0 0
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Timepoint [3] 0 0
Up to 24 Months
Secondary outcome [1] 0 0
Overall Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Timepoint [1] 0 0
Up to 24 Months
Secondary outcome [2] 0 0
Area Under the Concentration-Time Curve
Timepoint [2] 0 0
Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days.
Secondary outcome [3] 0 0
Maximum Plasma Concentration (Cmax)
Timepoint [3] 0 0
Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days.
Secondary outcome [4] 0 0
Trough Concentration (CTrough)
Timepoint [4] 0 0
Cycle 1 Day 1: pre-dose, 0.5, and 2 hours post-dose. Cycle length= 21 days.
Secondary outcome [5] 0 0
Number of Participants Experiencing a Dose-Limiting Toxicity (DLT)
Timepoint [5] 0 0
At the end of Cycle 1 (cycle length is 21 days)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2016
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
24/01/2025
Actual
Sample size
Target
492
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT02964013
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries