Advanced hepatocellular carcinoma without any prior systemic treatment. MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: MK-1308A (Coformulated MK 1308/MK 3475)
Pharmaceutical Form: Solution for infusion
Current Sponsor code: MK-1308
Other descriptive name: MK-1308
Concentration unit: mg/ml milligram(s)/mi
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has an HCC diagnosis confirmed by radiology, histology, or cytology (fibrolamellar and mixed hepatocellular/ cholangiocarcinoma subtypes are not eligible). - Radiologic confirmation of diagnosis is provided by the study site and confirmed by BICR. Clinically confirmed diagnosis of HCC as per the AASLD criteria, which requires: o Radiographically evident cirrhosis AND o A liver mass that shows arterial phase hyperenhancement on triphasic CT or MRI, AND EITHER: - Is =20 mm with either nonperipheral portal washout or an enhancing capsule OR - Is 10-19 mm with nonperipheral portal venous washout AND an enhancing capsule 2. Has BCLC Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach. 3. Has a Child-Pugh class A liver score within 7 days prior to first dose of study intervention. 4. Has a predicted life expectancy of >3 months. 5. Has at least 1 measurable HCC lesion based on RECIST 1.1, confirmed by BICR. 6. Has an ECOG PS of 0 to 1 within 7 days prior to first dose of study intervention. 7. Is at least 18 years of age at the time of providing documented informed consent. 8. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 7 days after receiving the last dose of lenvatinib: - 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 ) - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study drugs is more stringent than the requirements above, the local label requirements should be followed. 9. 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), with low user dependency, 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 MK-1308A and 30 days after lenvatinib, whichever occurs last 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 24 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. 10. The participant (or legally acceptable representative) has provided documented informed consent/assent for the study. 11. Participants with past or ongoing HCV infection will be eligible for the study. The treated participants must have completed their treatment at least 1 month prior to starting study intervent
Exclusion criteria
Exclusion criteria: 1. Has had esophageal or gastric variceal bleeding within the last 6 months. All participants will be screened for esophageal or gastric varices unless such screening has been performed in the past 3 months before first dose of treatment. If varices are present, they should be treated according to institutional standards before starting study intervention; esophageal or gastric varices that require interventional treatment within 28 days prior to first dose of study drug are excluded. 2. Has bleeding or thrombotic disorders or use of factor X inhibitors or anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar agents. Treatment with low molecular weight heparin is permitted. 3. Has clinically apparent ascites on physical examination. 4. Has inferior vena cava or cardiac involvement of HCC based on imaging, confirmed by BICR. 5. Has had clinically diagnosed hepatic encephalopathy in the last 6 months unresponsive to therapy. Participants on rifaximin or lactulose during Screening to control their hepatic encephalopathy are not allowed. 6. Has medical contraindications that preclude all forms of contrast-enhanced imaging (CT or MRI). 7. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib 8. Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula. 9. Has active hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study drug. 10. Has clinically significant cardiovascular impairment within 12 months of the first dose of study intervention. 11. Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention. 12. Has had a minor surgery (ie, simple excision) within 7 days prior to the first dose of study intervention (Cycle 1 Day 1). 13. Has serious nonhealing wound, ulcer, or bone fracture. 14. Has received any systemic chemotherapy, including anti-VEGF therapy, or any systemic investigational anticancer agents for treatment of HCC. 15. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, or CD137). 16. Has received locoregional therapy to liver (transcatheter chemoembolization, transcatheter embolization, hepatic arterial infusion, radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study intervention. 17. Has received prior radiotherapy to a nonliver region within 2 weeks of start of study intervention. 18. Has received a live or live-attenuated vaccine within 30 days before the first dose of study drug. 19. 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. 20. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention. 21. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 22. Has a known history of, or any evidence of, CNS metastases and/or carcinomatous meningitis as assessed by local site investigator. 23. Has severe hypersensitivity (=Grade 3) to study intervention and/or any of th
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To assess the safety and tolerability of study intervention with MK- 1308A/lenvatinib. 2. To evaluate the efficacy of MK-1308A/lenvatinib with respect to objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).;Secondary Objective: 1. To evaluate the efficacy of MK-1308A/lenvatinib with respect to duration of response (DOR) per RECIST 1.1 as assessed by BICR. 2. To evaluate the efficacy of MK-1308A/lenvatinib with respect to disease control rate (DCR) per RECIST 1.1 as assessed by BICR. 3. To evaluate the efficacy of MK-1308A/lenvatinib with respect to progression-free survival (PFS) per RECIST 1.1 as assessed by BICR. 4. To evaluate the efficacy of MK-1308A/lenvatinib with respect to time to progression (TTP) per RECIST 1.1 as assessed by BICR. 5. To evaluate the efficacy of MK-1308A/lenvatinib with respect to overall survival (OS). 6. To evaluate efficacy outcomes of MK-1308A/lenvatinib per modified RECIST (mRECIST) assessed by BICR. ;Primary end point(s): 1. Number of participants with a Dose-Limiting Toxicity (DLT) in the Safety Lead-in Phase 2. Number of participants with =1 adverse event (AE) 3. Number of participants with =1 serious adverse event (SAE) 4. Number of participants with =1 immune-related AE (irAE) 5. Number of participants with =1 hepatic AEs 6. Number of participants discontinuing study treatment due to an AE 7. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR);Timepoint(s) of evaluation of this end point: 1. Cycle 1 (Up to approximately 3 weeks) 2. Up to approximately 5 years 3. Up to approximately 5 years 4. Up to approximately 5 years 5. Up to approximately 5 years 6. Up to approximately 5 years 7. Up to approximately 5 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Duration of Response (DOR) per RECIST 1.1 as assessed by BICR 2. Disease Control Rate (DCR) per RECIST 1.1 as assessed by BICR 3. Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR 4. Time-To-Progression (TTP) per RECIST 1.1 as assessed by BICR 5. Overall Survival (OS) 6. ORR per modified RECIST (mRECIST) as assessed by BICR 7. DOR per mRECIST as assessed by BICR 8. DCR per mRECIST as assessed by BICR 9. PFS per mRECIST as assessed by BICR 10. TTP per mRECIST as assessed by BICR;Timepoint(s) of evaluation of this end point: 1. Up to approximately 28 months 2. Up to approximately 28 months 3. Up to approximately 28 months 4. Up to approximately 28 months 5. Up to approximately 28 months 6. Up to approximately 28 months 7. Up to approximately 28 months 8. Up to approximately 28 months 9. Up to approximately 28 months 10. Up to approximately 28 months | — |
Countries
China, Italy, Japan, Korea, Republic of, Poland, Russian Federation, Spain, Switzerland, Taiwan, Turkey, Ukraine, United States
Outcome results
None listed