Phase 2 Study of MK 1308A (Coformulated MK 1308/MK-3475), plus Lenvatinib (E7080/MK-7902) in First-line Therapy of Advanced Hepatocellular Carcinoma

Phase 1

Conditions: Advanced hepatocellular carcinoma without any prior systemic treatment
MedDRA version: 20.0Level: PTClassification code 10073071Term: Hepatocellular carcinomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2020-004490-52-IT

Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 110

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: Radiographically evident cirrhosis o A liver mass that shows arterial phase hyperenhancement on triphasic CT or MRI, AND EITHER:
- > =20 mm with either nonperipheral portal washout or an enhancing capsule
- 10-19 mm with nonperipheral portal venous washout AND anenhancing 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 (abstinent on a long-term and persistent basis) and agree to remain abstinent
- Use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause )
9. A female participant is eligible to participate if she is not pregnant or breastfeeding, or is not a WOCBP 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 (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.
10. Il partecipante (o un rappresentante legalmente riconosciuto) ha fornito documentato il consenso/assenso informato per lo studio.
11. Participants with past or ongoing HCV infection will be eligible. The treated participants must have completed their treatment at least 1 month prior to starting study intervention.
12. Participants with controlled hepatitis B will be eligible as long as:
- Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be < 500 IU/mL prior to first dose of study drug.
Participants on active HBV therapy with viral loads <100 IU/mL should stay on the same therapy throughout study intervention.
- Participants positive for antihepatitis B core antibody HBc, negative for HBsAg, and negative or positive for antihepatitis B surface antibody (HBs), with an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis.
13. Has adequately controlled BP with or without antihypertensive medications, defined as BP =150/90 mm Hg at Screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.
14. Has adequate organ function defined in the study protocol
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 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

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 contrastenhanced imaging (CT or MRI).
7. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
8. Has a preexisting Grade =3 gastrointestinal or non-gastrointestinal fistula.
9. Has clinically significant 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-PDL2 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 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 additional malignancy that is progressing or has required active treatment within the past 3 years.
22. Has a known history of CNS metastases and/or carcinomatous meningitis as assessed by local site investigator.
For more exclusion criteria see the protocol

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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