Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

A Study of Intratumoral/Intralesional Administration of V938 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced/Metastatic or Recurrent Malignancies (V938-001)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04135352
Recruitment Status : Recruiting
First Posted : October 22, 2019
Last Update Posted : November 14, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
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 establish a preliminary recommended Phase 2 dose (PRP2D) of V938 administered in combination with pembrolizumab.

Condition or disease Intervention/treatment Phase
Neoplasm Metastasis Drug: 200 mg of pembrolizumab Biological: V938 Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : November 4, 2019
Estimated Primary Completion Date : January 24, 2022
Estimated Study Completion Date : January 24, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: V938 Dose A + 200 mg of pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose A of V938 intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
Drug: 200 mg of pembrolizumab
Participants receive 200 mg of pembrolizumab intravenously on day 1 of every 21-day cycle for 35 cycles.
Other Name: MK-3475

Biological: V938
Participants receive V938 intratumorally in the first 21-day cycle.

Experimental: V938 Dose B + 200 mg of pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose B of V938 intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
Drug: 200 mg of pembrolizumab
Participants receive 200 mg of pembrolizumab intravenously on day 1 of every 21-day cycle for 35 cycles.
Other Name: MK-3475

Biological: V938
Participants receive V938 intratumorally in the first 21-day cycle.

Experimental: V938 Dose C + 200 mg of pembrolizumab
This arm will enroll participants with advanced/metastatic or recurrent solid tumors. Participants receive Dose C of V938 intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
Drug: 200 mg of pembrolizumab
Participants receive 200 mg of pembrolizumab intravenously on day 1 of every 21-day cycle for 35 cycles.
Other Name: MK-3475

Biological: V938
Participants receive V938 intratumorally in the first 21-day cycle.

Experimental: Arm A: Dose Confirmation, 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 preliminary recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
Drug: 200 mg of pembrolizumab
Participants receive 200 mg of pembrolizumab intravenously on day 1 of every 21-day cycle for 35 cycles.
Other Name: MK-3475

Biological: V938
Participants receive V938 intratumorally in the first 21-day cycle.

Experimental: Arm B: Dose Confirmation, 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 preliminary recommended Phase 2 Dose, determined by analysis of the Dose A-C arms, intratumorally in cycle 1. Participants also receive 200 mg of pembrolizumab intravenously on day 1 of every cycle beginning with cycle 2 for a maximum of 35 cycles. Each cycle is 21 days.
Drug: 200 mg of pembrolizumab
Participants receive 200 mg of pembrolizumab intravenously on day 1 of every 21-day cycle for 35 cycles.
Other Name: MK-3475

Biological: V938
Participants receive V938 intratumorally in the first 21-day cycle.




Primary Outcome Measures :
  1. 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.

  2. Number of Participants Who Experience ≥1 Adverse Event (AE) [ Time Frame: Up to 2 years ]
    The number of participants who experience ≥1 adverse event will be reported.

  3. Number of Participants Who Discontinue Study Drug Due to an Adverse Event (AE) [ Time Frame: Up to 2 years ]
    The number of participants who discontinue study drug due to an adverse event will be reported.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Up to 2 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.

  2. 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. 2-4 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.

  3. 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. 2-4 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.

  4. 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, 4, and 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.

  5. V938 Excretion: Infectivity [ Time Frame: Predose cycle 1 on 3 separate days, and cycles 3, 5, 8, 9, and 10 on day 1. 2, 4, and 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • For Dose-escalation Phase (Doses A-C): Have a histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, or been ineligible for treatments known to confer clinical benefit.
  • For Dose Confirmation Arm A: Have a histologically or cytologically confirmed Stage III (unresectable) or Stage IV cutaneous melanoma and have received, been intolerant to, or been ineligible for treatments known to confer clinical benefit.
  • For Dose Confirmation Arm B: Have a histologically or cytologically confirmed advanced head and neck squamous cell carcinoma (HNSCC) and have received, been intolerant to, or been ineligible for treatment known to confer clinical benefit.
  • For Dose Confirmation Arms A and B: Have at least 1 lesion that is amenable to both intratumoral injection and biopsy.
  • For all arms: Have at least 1 cutaneous or subcutaneous lesion amenable to intratumoral injection, and have at least 1 distant and/or discrete noninjected lesion that is measurable per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) criteria.
  • For all arms, the injectable lesion must be measurable and meet protocol-specified size criteria.
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  • Demonstrate 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: Refrain from donating sperm; PLUS 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.
  • Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one 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.
  • Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04135352


Contacts
Layout table for location contacts
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
Layout table for location information
Israel
Rambam Medical Center ( Site 0020) Recruiting
Haifa, Israel, 3109601
Contact: Study Coordinator    +97247773003      
Chaim Sheba Medical Center ( Site 0021) Recruiting
Ramat Gan, Israel, 5265601
Contact: Study Coordinator    +97235302241      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: Medical Director Merck Sharp & Dohme Corp.

Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04135352    
Other Study ID Numbers: V938-001
V938-001 ( Other Identifier: Merck Protocol Number )
First Posted: October 22, 2019    Key Record Dates
Last Update Posted: November 14, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme Corp.:
Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents