Advanced/metastatic solid tumors MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has locally-advanced disease that is not amenable to surgery or radiation, or Stage IV advanced/metastatic solid tumor malignancies 2. Has histologically- or cytologically-confirmed diagnosis of an advanced/metastatic solid tumor 3. Has measurable disease by RECIST 1.1 criteria as assessed by investigator. Target lesions in a previously irradiated area will be considered measurable if progression has been demonstrated in such lesions 4. Has submitted a baseline tumor sample for analysis (either de novo biopsy or an archival tumor block) 5. Has a performance status of 0 or 1 on the ECOG Performance Scale obtained within 72 hours prior to the first dose of study intervention 6. If participants have known HIV-positive disease, participants must have well-controlled HIV on ART defined as: a. CD4+ T-cell count >350 cells/mm3 at the time of screening b. Must have achieved and maintained virologic suppression, defined as HIV RNA levels below 50, or LLOQ (below limits of detection), using a locally available assay at the time of screening c. Must be on a stable regimen without any changes in drugs or dose modifications for a minimum of 4 weeks prior to study entry (Day 1) 7. Demonstrate adequate organ function 8. Is male or female, from =18 years of age inclusive, at the time of signing the informed consent 9. Male participants are eligible to participate if they agree to the following during the intervention period for and for at least 120 days after the last dose of study intervention: PLUS either: - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR - Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause) as detailed below: Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant 10. A 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 WOCBP OR - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), 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. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention - A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 72 hours before the first dose of study intervention - If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive 11. The participant (or legally acceptable representative) provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.
Exclusion criteria
Exclusion criteria: 1. Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) prior to first dose of study intervention, or has not recovered to CTCAE Grade 1 or better 2. If major or minor surgery was performed at/near the area being considered for injection, participant must be recovered from toxicity and/or complications of intervention 3. Has had injection, or radiation therapy of >30 Gy, participant must be recovered from toxicity and/or complications of intervention 4. Has a history of second malignancy, unless potentially curative treatment has been completed with no further evidence of malignancy 5. Has known active CNS metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate if lesions are radiologically stable 6. Has an active infection requiring therapy 7. Has a history of interstitial lung disease 8. Has a history of noninfectious pneumonitis requiring active steroid therapy or ongoing pneumonitis 9. Has an active autoimmune disease that required systemic treatment in the past 2 years (ie, necessitating use of disease modifying agents, corticosteroids, or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy such as thyroxine, insulin, or physiologic corticosteroid replacement therapy (steroid use =10 mg prednisone, or its equivalent, daily) is not considered a form of systemic treatment and is allowed. The use of non-systemic steroids is permitted 10. Participants with known Hepatitis B or C infections or known to be positive for HBsAg/HBV DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay 11. Participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease 12. Has known hypersensitivity to V937 and/or pembrolizumab or any of their excipients 13.Has known psychiatric or substance abuse disorder that significantly interferes with cooperation with requirements of the trial 14. Has received prior therapy with anti-PD-1/PD-L1 agents, T-VEC or any other oncolytic virus therapies 15. Has received a live vaccine within 30 days prior to first dose of study drug. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are permitted. However, intranasal influenza (eg, FluMist®) and OPV vaccines are live attenuated vaccines and not permitted 16. 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 intervention 17. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the objective response rate (ORR) of V937 administered in subcutaneous tumors in combination with pembrolizumab per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the investigator. 2. To determine the safety and tolerability and to establish a preliminary recommended phase 2 dose (RP2D) of V937 administered in visceral tumors in combination with pembrolizumab. ;Secondary Objective: 1. To determine the safety and tolerability of V937 administered in subcutaneous tumors in combination with pembrolizumab. 2. To evaluate progression free survival (PFS), and duration of response (DOR) of participants treated with V937 in subcutaneous tumors in combination with pembrolizumab per RECIST 1.1 as assessed by the investigator. 3. To evaluate the ORR, PFS and DOR of V937 administered in subcutaneous tumors in combination with pembrolizumab per RECIST 1.1 for immune-based therapeutics (iRECIST) criteria as assessed by the investigator. 4. To evaluate overall survival (OS) of participants treated with V937 in subcutaneous tumors in combination with pembrolizumab. 5. To evaluate the ORR of V937 administered in visceral tumors at the preliminary RP2D with pembrolizumab per RECIST 1.1 and iRECIST criteria as assessed by the investigator.;Primary end point(s): 1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator;Timepoint(s) of evaluation of this end point: 1. Up to approximately 5 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Number of Participants Who Experienced One or More Adverse Events (AEs) 2. Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE) 3. Number of Participants who Experience a Dose-Limiting Toxicity (DLT) 4. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator 5. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Investigator 6. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator 7. Progression-Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator 8. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors 1.1 for Immune-Based Therapeutics (iRECIST) as Assessed by Investigator 9. Overall Survival (OS);Timepoint(s) of evaluation of this end point: 1. Up to approximately 107 weeks. 2. Up to approximately 103 weeks. 3. Up to approximately 107 weeks. 4. Up to approximately 5 years. 5. Up to approximately 5 years. 6. Up to approximately 5 years. 7. Up to approximately 5 years. 8. Up to approximately 5 years. 9. Up to approximately 5 years. | — |
Countries
Brazil, Canada, Colombia, France, Germany, Hungary, Israel, Italy, Korea, Republic of, Norway, Peru, Poland, Portugal, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
Outcome results
None listed