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

NCT04135352 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: V938-0012020-003431-25
• Study Type: interventional
• Target: 35
• Locations: 3 countries
• Sites: 6

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 identify a recommended Phase 2 dose (RP2D) of V938 administered in combination with pembrolizumab.

Conditions

Neoplasm Metastasis

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced Dose-Limiting Toxicity (DLT)

  DLT was defined as a treatment-related adverse event (AE) including the following: Grade (Gr) 4 nonhematologic toxicity (not laboratory), Gr 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or Gr 4 thrombocytopenia of any duration or Gr 3 thrombocytopenia associated with clinically significant bleeding, Gr 3 non-hematological AE with the exception of fatigue lasting ≤72 hours, Gr 3 nausea, vomiting, diarrhea or rash, any Gr 3 or Gr 4 nonhematologic that lead to hospitalization or abnormality persisting for \>1 week or resulting in a drug induced liver injury (DILI), febrile neutropenia Gr 3 or Gr, prolonged delay (\>2 weeks) in initiating cycle 3 (for Cohorts 1-4) or cycle 2 (for cohorts 2a-4a) due to study intervention-related toxicity, intervention-related toxicity that caused study discontinuation or missing \>1 injection of V938 as a result of drug-related AE(s) during the first 2 cycles (for cohorts 1-4) or during the first cycle (for cohort 2a-4a), Gr 5 toxicity

  Up to ~ 42 days for cohort 1, 2, 3 and 4; Up to ~ 21 days for cohorts 3a and 4a

• Number of Participants Who Experienced an Adverse Event (AE)

  Number of participants who experienced an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment

  Up to ~ 28 months

• Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE)

  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed.

  Up to ~ 25 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to ~ 33 months

• Area Under the Concentration-Time Curve From 0 to 6 Hours Postdose (AUC0-6) for V938 Ribonucleic Acid (RNA) in Plasma

  Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.

• Maximum Concentration (Cmax) of V938 Ribonucleic Acid (RNA) in Plasma

  Cycle 1 (C1) Day1 (D1), C1D8 and C2D1. Each Cycle is 21 days.

• Number of Participants With Newcastle Disease Virus (NDV) RNA Shedding Per Polymerase Chain Reaction (PCR)

  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.

• Number of Participants With NDV Infectivity in Excretory Tissue Samples

  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.

Study Arms (9)

V938 Dose A + delayed pembrolizumab

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

V938 Dose B + delayed pembrolizumab

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

V938 Dose C + delayed pembrolizumab

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

V938 Dose D + delayed pembrolizumab

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

V938 Dose B + immediate pembrolizumab

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

V938 Dose C + immediate pembrolizumab

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

V938 Dose D + immediate pembrolizumab

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

Dose Expansion Arm A, Melanoma

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

Dose Expansion Arm B, HNSCC

EXPERIMENTAL

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.

Drug: 200 mg of pembrolizumab; Biological: V938

Interventions

200 mg of pembrolizumab DRUG

Participants receive 200 mg of pembrolizumab intravenously Q3W for a maximum of 35 21-day cycles.

Also known as: MK-3475

Dose Expansion Arm A, Melanoma; Dose Expansion Arm B, HNSCC; V938 Dose A + delayed pembrolizumab; V938 Dose B + delayed pembrolizumab; V938 Dose B + immediate pembrolizumab; V938 Dose C + delayed pembrolizumab; V938 Dose C + immediate pembrolizumab; V938 Dose D + delayed pembrolizumab; V938 Dose D + immediate pembrolizumab

V938 BIOLOGICAL

Participants receive V938 intratumorally in cycles 1-7. Each cycle is 21 days.

Dose Expansion Arm A, Melanoma; Dose Expansion Arm B, HNSCC; V938 Dose A + delayed pembrolizumab; V938 Dose B + delayed pembrolizumab; V938 Dose B + immediate pembrolizumab; V938 Dose C + delayed pembrolizumab; V938 Dose C + immediate pembrolizumab; V938 Dose D + delayed pembrolizumab; V938 Dose D + immediate pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (6)

UCSF Helen Diller Family Comprehensive Cancer Center ( Site 0002)

San Francisco, California, 94158, United States

Location

MD Anderson Cancer Center ( Site 0001)

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute ( Site 0004)

Salt Lake City, Utah, 84112, United States

Location

Princess Margaret Cancer Centre ( Site 0010)

Toronto, Ontario, M5G 2M9, Canada

Location

Rambam Health Care Campus-Oncology Division ( Site 0020)

Haifa, 3109601, Israel

Location

Chaim Sheba Medical Center ( Site 0021)

Ramat Gan, 5265601, Israel

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Neoplasm Metastasis; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2019
• First Posted: October 22, 2019
• Study Start: November 4, 2019
• Primary Completion: August 24, 2022
• Study Completion: August 24, 2022
• Last Updated: November 12, 2024
• Results First Posted: November 12, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (3); IL (2)