Advanced solid tumors MedDRA version: 21.1 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A participant will be eligible for inclusion in the study if the participant: 1. Has histologically or cytologically confirmed, advanced (unresectable or metastatic) solid tumor as follows: • Squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix • Endometrial cancer • Head and neck squamous cell carcinoma (HNSCC) • Unresectable biliary adenocarcinoma (gallbladder or biliary tree [intrahepatic or extrahepatic] cholangiocarcinoma) • Adenocarcinoma or squamous cell carcinoma of the esophagus or advanced/metastatic Siewert type 1 adenocarcinoma of the gastroesophageal junction (GEJ). • Triple-negative breast cancer (TNBC) • Hepatocellular carcinoma (HCC) • Urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra • Ovarian cancer • Gastric cancer 2. Has measurable disease per RECIST 1.1 as assessed by the BICR (Cohort A1 only) or local site investigator/radiology (all other cohorts). 3. Can provide a newly obtained core or excisional biopsy of a tumor lesion 4. Is male or female, who is at least 18 years of age at the time of signing the informed consent. 5. Has an ECOG Performance Status of either 0 or 1 (ECOG PS of 2 allowed for Cohort H only), as assessed within 7 days before starting study intervention. 6. Has a predicted life expectancy of at least 3 months. 7. Male participants must agree to follow contraceptive guidance 8. Female participants are not pregnant or breastfeeding, not women of child-bearing potential (WOCBP) or are WOCBP and agree to follow contraceptive guidance. 9. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. 10. Has adequately controlled BP with or without antihypertensive medications, Note: this criterion only applies to participants who will receive lenvatinib 11. HIV-infected participants must have well controlled HIV on ART 12. Participants who are HbsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization/allocation. 13. Participants with history of HCV infection are eligible if HCV viral load is undetectable at Screening. 14. Has adequate organ function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 244 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 366
Exclusion criteria
Exclusion criteria: Participant must be excluded from the study if the participant: 1. Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years 2. HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease 3. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-TIGIT agent 4. Has received prior systemic anticancer therapy including investigational agents within 4 weeks. Note: This does not include leadin chemotherapy in Cohort I 5. Has received prior radiotherapy within 2 weeks or radiation-related toxicities requiring corticosteroids 6. Has received a live or live-attenuated vaccine within 30 days 7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days 8. Has known active CNS metastases and/or carcinomatous meningitis 9. Known severe hypersensitivity (=Grade 3) to study medication or any of their excipients 10. Has an active autoimmune disease that has required systemic treatment in past 2 years 11. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease 12. Has an active infection requiring systemic therapy 13. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation 14. Has present accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks 15. Has concurrent active hepatitis B and hepatitis C infection 16. Has not adequately recovered from major surgery 17. Participants unlikely to comply with the requirements of the study 18. Has had an allogenic organ transplant 19. Has received an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention All Cohorts except B1: 20. Has known MSI-H or MMR deficient cancer Cohort B1 and B2 only: 21. Greater than 1 prior systemic chemotherapy regimen For participants who will receive Lenvatinib: Cohort B2 & G: 22. Has had major surgery within 3 weeks 23. Has current, clinically relevant =Grade 3 fistula 24. Has urine protein =1 g/24 hours 25. Has a LVEF below the normal range 26. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation 27. Has prolongation of QTc interval to >480 ms 28. Has clinically significant cardiovascular disease within 12 months 29. Has serious nonhealing wound, ulcer, or bone fracture 30. Has GI malabsorption 31. Has active hemoptysis 32. Has had esophageal or gastric variceal bleeding within the last 6 months (G only) Cohort D2: 33. Has had previous systemic therapy for advanced or unresectable biliary tract cancer Cohort F: 34. Has a history of class II-IV congestive heart failure or myocardial infarction within 6 months Cohort H: 35. Has disease suitable for local therapy administered with curative intent 36. Is receiving hemodialysis Cohort I: 37. Has mucinous, germ cell, or borderline tumor of the ovary 38. Has ongoing Grade 3 or 4 toxicity, excluding alopecia, followingchemotherapy administered during the Lead-in Period 39. Has received colony-stimulating factors within 4 weeks prior to receiving chemotherapy during the Lead-in Period 40. Is considered to be of poor medical risk due to
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare MK-7684A to pembrolizumab alone with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR) in participants with cervical cancer enrolled in Cohort A1. 2. To compare MK-7684A to pembrolizumab alone with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by BICR in participants with cervical cancer enrolled in Cohort A1. 3.To evaluate MK-7684A alone or with anticancer therapies with respect to ORR per RECIST 1.1 as assessed by the investigator in participants with selected solid tumors. 4. To evaluate MK-7684A in combination with anticancer therapies with respect to PFS per RECIST 1.1 at 9 months (PFS-9) and 12 months (PFS- 12) as assessed by the investigator in participants with previously untreated advanced epithelial ovarian cancer enrolled in Cohort I.;Secondary Objective: 1. To evaluate MK-7684A alone or with other anticancer therapies for overall survival (OS). 2. To evaluate MK-7684A alone or with other anticancer therapies for PFS per RECIST 1.1, per investigator in participants with selected solid tumors. 3. To evaluate MK-7684A alone for duration of response per RECIST 1.1, per BICR in participants in Cohort A1. 4. To evaluate MK-7684A alone or with other anticancer therapies for DOR per RECIST 1.1, per investigator in participants with selected solid tumors. 5. To compare MK-7684A to pembrolizumab for ORR per RECIST 1.1, per investigator in participants with cervical cancer enrolled in Cohort A1. 6. To compare MK-7684A to pembrolizumab for PFS per RECIST 1.1, per investigator in participants with cervical cancer enrolled in Cohort A1. 7. To evaluate change from baseline in health-related quality-of-life (HRQoL) in participants enrolled in Cohort A1. 8. To evaluate the safety and tolerability of MK-7684A alone or with other anticancer therapies.;Primary end point(s): 1. Objective Response Rate (ORR) per Re | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Survival (OS). 2. PFS per RECIST 1.1 as Assessed by Investigator. 3. Duration of Response (DOR) per RECIST 1.1 as Assessed by BICR. 4. DOR per RECIST 1.1 as Assessed by Investigator. 5. ORR per RECIST 1.1 as Assessed by Investigator 6. Change from Baseline in Physical Functioning Score (EORTC QLQ-C30 Items 1-5). 7. Number of Participants Who Experienced One or More Adverse Events (AEs). 8. Number of Participants Who Discontinued Study Intervention Due to an AE.;Timepoint(s) of evaluation of this end point: 1. Up to approximately 5.5 years. 2. Up to approximately 2 years. 3. Up to approximately 2 years. 4. Up to approximately 2 years. 5. Up to approximately 2 years. 6. Baseline and up to approximately 2 years. 7. Baseline and up to approximately 2 years. 8. Up to approximately 2 years. 9. Up to approximately 2 years. | — |
Countries
Canada, Chile, Colombia, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Taiwan, Türkiye, United States
Outcome results
None listed