- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04135352
A Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies (V938-001)
November 1, 2022 updated by: Merck Sharp & Dohme LLC
A Phase 1/1b, Open-label Clinical Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics, and V938 shedding in participants with advanced/metastatic or recurrent malignancies who receive V938 in combination with pembrolizumab (MK-3475).
The primary objective is to determine the safety and tolerability and to identify a recommended Phase 2 dose (RP2D) of V938 administered in combination with pembrolizumab.
Study Overview
Status
Terminated
Conditions
Intervention / Treatment
Detailed Description
Due to discontinuation of V938-001, all ongoing participants who completed V938 plus pembrolizumab treatment may be enrolled in an extension study (KN587) to continue pembrolizumab monotherapy for a total of 35 cycles since the first dose in V938-001 and to be monitored as appropriate.
Study Type
Interventional
Enrollment (Actual)
35
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Cancer Centre ( Site 0010)
-
-
-
-
-
Haifa, Israel, 3109601
- Rambam Health Care Campus-Oncology Division ( Site 0020)
-
Ramat Gan, Israel, 5265601
- Chaim Sheba Medical Center ( Site 0021)
-
-
-
-
California
-
San Francisco, California, United States, 94158
- UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0002)
-
-
Texas
-
Houston, Texas, United States, 77030
- MD Anderson Cancer Center ( Site 0001)
-
-
Utah
-
Salt Lake City, Utah, United States, 84112
- Huntsman Cancer Institute ( Site 0004)
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- For Dose-escalation arms (Doses A-D): Have a histologically confirmed advanced/metastatic solid tumor and have received, been intolerant to, or been ineligible for treatments known to confer clinical benefit.
- For Dose Expansion Arm A: Have a histologically confirmed Stage III (unresectable) or Stage IV cutaneous melanoma and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic melanoma which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy.
- For Dose Expansion Arm B: Have a histologically confirmed advanced head and neck squamous cell carcinoma (HNSCC) and have received and progressed following 1 or 2 prior lines of systemic treatments for metastatic HNSCC which must include 1 line of treatment with PD-1 or PD-L1 immune checkpoint inhibitor either as monotherapy or in combination with other therapy.
- For Dose Expansion Arms A and B: Have at least 1 lesion that is amenable to both intratumoral (IT) injection and biopsy and have at least 1 distant and/or discrete noninjected lesion that is measurable per RECIST 1.1 criteria.
- For Dose-escalation Cohorts 2a, 3a, or 4a and Expansion Cohorts (Arms A and B) ONLY: Have baseline biopsy performed from 1 of the injectable lesions that are planned for IT injection and with tumor tissue provided.
For all arms: Have at least 1 cutaneous or subcutaneous lesion amenable to IT injection and must be measurable and meet 1 of the following criteria per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1):
- A cutaneous or subcutaneous lesion ≥1 cm in longest diameter for solid tumors, or ≥1.5 cm in short axis for a nodal lesion in participants with solid tumor. The longest diameter for an injectable lesion must be ≤10 cm for both solid tumors and nodal lesions in participants with solid tumors.
- Multiple coalescing, superficial lesions that in aggregate have a longest diameter of ≥1 cm and ≤10 cm.
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
- Show adequate organ function.
- Male participants are eligible to participate if they agree to the following during the intervention period and for at least 120 days: either be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR must agree to use contraception unless confirmed to be azoospermic. Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies:
- Is not a woman of childbearing potential (WOCBP)
- Is a WOCBP and using a contraceptive method that is highly effective, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention.
- HIV-infected participants must have well controlled HIV on antiretroviral therapy (ART), per study criteria.
Exclusion Criteria:
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to the first dose of study intervention or has not recovered from any adverse events (AEs) that were due to cancer therapeutics administered more than 4 weeks earlier. Participants receiving ongoing replacement hormone therapy for endocrine immune-related AEs will not be excluded from participation in this study.
- Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer or in situ cervical cancer, or other in-situ cancers.
- Has clinically active central nervous system metastases and/or carcinomatous meningitis.
- Has had a severe hypersensitivity reaction to treatment with the monoclonal antibody/components of the study intervention or has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3).
- Has an active infection requiring therapy.
- Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy.
- Is on chronic systemic steroid therapy in excess of replacement doses (prednisone ≤10 mg/day is acceptable), or on any other form of immunosuppressive medication.
- Participants with known Hepatitis B or C infections or known to be positive for hepatitis B antigen/hepatitis B virus DNA or hepatitis C antibody or RNA.
- HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
- Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
- Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.
- Has not fully recovered from any effects of major surgery without significant detectable infection.
- Has received a live-virus vaccine within 30 days of planned treatment start.
- Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days of administration of V938.
- Has a history of re-irradiation for HNSCC at the projected injection site.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: V938 Dose A + delayed pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors.
Participants receive Dose A of V938 intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously once every 3 weeks (Q3W) beginning with cycle 2 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: V938 Dose B + delayed pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors.
Participants receive Dose B of V938 intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: V938 Dose C + delayed pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors.
Participants receive Dose C of V938 intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: V938 Dose D + delayed pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors.
Participants receive Dose D of V938 intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 2 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: V938 Dose B + immediate pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors.
Participants receive Dose B of V938 intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: V938 Dose C + immediate pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors.
Participants receive Dose C of V938 intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: V938 Dose D + immediate pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors.
Participants receive Dose D of V938 intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: Dose Expansion Arm A, Melanoma
This arm will enroll only participants with with a diagnosis of stage III (unresectable) and Stage IV melanoma (any line of therapy).
Participants receive V938 at the recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
Experimental: Dose Expansion Arm B, HNSCC
This arm will only enroll participants with a diagnosis of advanced/metastatic head and neck squamous cell carcinoma (HNSCC).
Participants receive V938 at the recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycles 1-7.
Participants also receive 200 mg of pembrolizumab intravenously Q3W beginning with cycle 1 for a maximum of 35 cycles.
Each cycle is 21 days.
|
Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.
Other Names:
Participants receive V938 intratumorally in cycles 1-7.
Each cycle is 21 days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Who Experience Dose-Limiting Toxicity (DLT)
Time Frame: Up to 42 days
|
The number of participants experiencing toxicities that are possibly, probably, or definitely related to study intervention administration will be reported.
|
Up to 42 days
|
Number of Participants Who Experience ≥1 Adverse Event (AE)
Time Frame: Up to approximately 28 months
|
The number of participants who experience ≥1 adverse event will be reported.
|
Up to approximately 28 months
|
Number of Participants Who Discontinue Study Drug Due to an Adverse Event (AE)
Time Frame: Up to approximately 25 months
|
The number of participants who discontinue study drug due to an adverse event will be reported.
|
Up to approximately 25 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response Rate (ORR)
Time Frame: Up to approximately 5 years
|
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions), as assessed by the investigator.
In solid tumors, assessment will be based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and modified RECIST 1.1 for immune-based therapeutics (iRECIST).
The percentage of participants who experience a CR or PR based on the above criteria will be presented.
|
Up to approximately 5 years
|
Area Under the Concentration-Time Curve from 0 to Infinity (AUC0-inf) for V938 Ribonucleic Acid (RNA) in Plasma
Time Frame: Predose cycle 1 on 4 separate days, cycles 2, 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 on 2 separate days, and cycle 2 on day 1. 2 to 4 hours postdose cycle 3 on day 1. 30 days after last dose. Each cycle is 21 days.
|
The AUC0-inf for V938 RNA in plasma will be calculated.
|
Predose cycle 1 on 4 separate days, cycles 2, 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 on 2 separate days, and cycle 2 on day 1. 2 to 4 hours postdose cycle 3 on day 1. 30 days after last dose. Each cycle is 21 days.
|
Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) Reached in Plasma
Time Frame: Predose cycle 1 on 4 separate days, cycles 2, 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 on 2 separate days, and cycle 2 on day 1. 2 to 4 hours postdose cycle 3 on day 1. 30 days after last dose. Each cycle is 21 days.
|
The Cmax for V938 RNA in plasma will be reported.
|
Predose cycle 1 on 4 separate days, cycles 2, 3, 5, 8, 9, and 10 on day 1. 2, 4, and 6 hours postdose cycle 1 on 2 separate days, and cycle 2 on day 1. 2 to 4 hours postdose cycle 3 on day 1. 30 days after last dose. Each cycle is 21 days.
|
V938 Excretion: Polymerase Chain Reaction (PCR)
Time Frame: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
|
The presence of V938, determined by PCR, in oral cavity/throat, urine, injection site, and anus will be reported.
|
Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
|
V938 Excretion: Infectivity
Time Frame: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
|
The presence of V938, determined by infectivity of V938, in oral cavity/throat, urine, injection site, and anus will be reported.
|
Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2 and 4-6 hours postdose cycle 1 day 1. Each cycle is 21 days.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
November 4, 2019
Primary Completion (Actual)
August 24, 2022
Study Completion (Actual)
August 24, 2022
Study Registration Dates
First Submitted
October 10, 2019
First Submitted That Met QC Criteria
October 18, 2019
First Posted (Actual)
October 22, 2019
Study Record Updates
Last Update Posted (Actual)
November 4, 2022
Last Update Submitted That Met QC Criteria
November 1, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- V938-001 (Other Identifier: Merck Protocol Number)
- 2020-003431-25 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neoplasm Metastasis
-
Betta Pharmaceuticals Co., Ltd.Recruiting
-
BayerCompleted
-
BayerCompletedNeoplasm Metastasis / Bone and BonesBelgium, Spain, Taiwan, United States, Japan, Russian Federation, Canada, Finland, Korea, Republic of, Singapore, Australia, Germany, Israel, United Kingdom, Italy, France, Poland, Brazil, Czechia, Norway, Sweden, Hong Kong
-
National Cancer Institute (NCI)TerminatedCancer | Neoplasm Metastasis | Metastasis | Neoplasm | Radiation OncologyUnited States
-
MedtronicNeuroCompletedMetastasis Spine | Metastasis to BoneUnited States, Luxembourg, Germany, France, Canada
-
Cho Ray HospitalUniversity of Medicine and Pharmacy at Ho Chi Minh CityRecruitingSynchronous Neoplasm | Liver Metastasis Colon CancerVietnam
-
Li MinRecruiting
-
Da FuGanzhou City People's HospitalRecruiting
-
University of Mississippi Medical CenterCompletedMetastasisUnited States
-
Assiut UniversityNot yet recruiting
Clinical Trials on 200 mg of pembrolizumab
-
Baptist Health South FloridaMerck Sharp & Dohme LLC; Miami Cancer InstituteCompletedSolid Tumor, AdultUnited States
-
Jair Bar, M.D., Ph.D.Merck Sharp & Dohme LLCCompletedNon Small Cell Lung Carcinoma | Stage II | Stage IIsrael
-
MedPacto, Inc.RecruitingCarcinoma, Non-Small-Cell LungKorea, Republic of
-
Gustave Roussy, Cancer Campus, Grand ParisRecruitingMetastatic Non-squamous Lung CancerFrance
-
Rakuten Medical, Inc.Active, not recruitingRecurrent Head and Neck Squamous Cell Carcinoma | Metastatic Head-and-neck Squamous-cell Carcinoma | Metastatic Cutaneous Squamous Cell Carcinoma | Locally Advanced Cutaneous Squamous Cell CarcinomaUnited States
-
Servier Bio-Innovation LLCMerck Sharp & Dohme LLC; Institut de Recherches Internationales ServierNot yet recruitingMSI-H/dMMR Gastroesophageal-junction Cancer | MSI-H/dMMR Gastric Cancer
-
University of South AlabamaExelixisTerminatedCervical Cancer | Metastatic Cervical Cancer | Recurrent Cervical Cancer | Persistent Cervical CancerUnited States
-
Inhibrx, Inc.Merck Sharp & Dohme LLCRecruitingMelanoma | Renal Cell Carcinoma | Head and Neck Cancer | Gastric Cancer | Non-Small Cell Lung Cancer | Solid Tumor | Urothelial CarcinomaUnited States
-
Yuhan CorporationCompleted
-
NovoCure GmbHMerck Sharp & Dohme LLCRecruiting