C97 Malignant neoplasms of independent (primary) multiple sites Malignant neoplasms of independent (primary) multiple sites
Conditions
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de 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 7. Demonstrate adequate organ function as defined in Table 7 (Refer to the Protocol) 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 (Refer to the Protocol) 10. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies (Refer to the Protocol) 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 12. Arm 1: Have at least one injectable lesion amenable to injection and/or biopsy. 13. Cohort A: Has locally recurrent, inoperable OR metastatic breast cancer treated with no more than 2 prior lines of therapy with skin involvement and/or subcutaneous lesions or accessible lymph nodes amenable to local injection 14. Cohort A: Has diagnosis of triple-negative breast cancer (estrogen receptor, progesterone receptor, and HER2-receptor negative status). 15. Cohort A: Has been treated with (neo)adjuvant anthracycline (unless anthracycline was contraindicated based on treating physician’s medical judgment) 16. Cohort B: Has histologically confirmed advanced or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx considered incurable and/or treated with no more than 1 previous line of therapy 17. Cohort B: Tumors must be PD-L1+ (CPS =1%) 18. Cohort B: Has documentation of HPV status for oropharyngeal cancers only. If HPV status has been previously determined, no retesting is required 19. Cohort C: Has histologically confirmed cSCC as the primary site of malignancy (metastatic skin involvement from another primary cancer or from cancers of unknown primary are not eligible). 20. Cohort C: Recurrent/metastatic disease only: Has metastatic disease defined as disseminated disease distant from the initial/primary site of diagnosis and/or with a history of locally-recurrent disease previously treated with surgery and/or radiotherapy, which is now incurable 21. Cohort C: Locally-advanced disease only: Participants ineligible for surgical resection. Contraindications to surgery are defined as: 22. Cohort C: Locally-advanced disease only: Received prior XRT to the index site or deemed ineligible for XRT. 23. Arm 2 part I: Has a histologically-confirmed advanced/metastatic solid tumor that has progressed on all treatment
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 (exceptions: HIV criteria outlined in Section 5.1.1 and HBV and HCV criteria for HCC cohort as stated in Section 5.1.4.1 of the protocol) 7. Has a history of interstitial lung dis 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 18.Has had esophageal or gastric variceal bleeding within the last 6 months. All participants should undergo screening for esophageal varices, unless such screening has been performed in the past 12 months before first dose of treatment. If varices are present, they should be treated
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response is a confirmed complete response (CR) or partial response (PR) NAME OF THE RESULT: ARM 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. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: An interim analysis will be conducted to enable future study planning at the Sponsor’s discretion and data will be examined on a continuous basis to allow for dose finding decision;•Dose limiting toxicity (DLT) • AE • Discontinuing a study intervention due to an AE NAME OF THE RESULT: ARM 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. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: An interim analysis will be conducted to enable future study planning at the Sponsor’s discretion and data will be examined on a continuous basis to allow for dose finding decision | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response is a confirmed complete response (CR) or partial response (PR) NAME OF THE RESULT: ARM 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. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: An interim analysis will be conducted to enable future study planning at the Sponsor’s discretion and data will be examined on a continuous basis to allow for dose finding decision;•Dose limiting toxicity (DLT) • AE • Discontinuing a study intervention due to an AE NAME OF THE RESULT: ARM 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. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: An interim analysis will be conducted to enable future study planning at the Sponsor’s discretion and data will be examined on a continuous basis to allow for dose finding decision;•Adverse event (AE) •Discontinuing a study ntervention due to an AE NAME OF THE RESULT: ARM 1: To determine the safety and tolerability of V937 administered in subcutaneous tumors in combination with pembrolizumab PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: An interim analysis will be conducted to enable future study planning at the Sponsor’s discretion and data will be examined on a continuous basis to allow for dose finding decision;ORR NAME OF THE RESULT: ARM 2: 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. PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMA | — |
Countries
Brazil, Canada, Colombia, France, Germany, Hungary, Israel, Japan, Norway, Peru, Russian Federation, Spain, Taiwan, United Kindgdom, United States
Outcome results
None listed