A Phase 3 Multicenter, Randomized, Double-blinded, Active-controlled, Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) with Pembrolizumab (MK-3475) in Combination with Transarterial Chemoembolization (TACE) Versus TACE in Participants with Incurable/Non-metastatic Hepatocellular Carcinoma (LEAP-012)
- Conditions
- Incurable / Non-metastatic Hepatocellular Carcinomaliver cancer10019815
- Registration Number
- NL-OMON52824
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 12
1. Has a diagnosis of HCC confirmed by radiology, histology, or cytology
(fibrolamellar and mixed hepatocellular/cholangiocarcinoma subtypes are not
eligible).
2. Has HCC localized to the liver without portal vein thrombosis, and not
amenable to curative treatment such as resection, ablation, or liver
transplant. No extrahepatic HCC is permitted, confirmed by BICR.
3. Has at least one measurable HCC lesion based on RECIST 1.1, confirmed by
BICR.
4. Has all lesions treatable with TACE in 1 or 2 (split-TACE) sessions.
5. Is amenable, without any contraindications, to the TACE procedure and
chemotherapy agent pre-specified at the study site.
6. Has a CP class A liver score within 7 days prior to first dose of study
intervention (see Appendix 10).
7. Has a predicted life expectancy of >3 months.
8. Has an ECOG PS of 0 to 1 within 7 days prior to first dose of study
intervention.
9. Is male or female >= 18 years of age at the time of signing the informed
consent.
10. Male participants are eligible to participate if they agree to the
following during the intervention period and for at least the time needed to
eliminate each study intervention after the last dose of study intervention.
The length of time required to continue contraception for each study
intervention is as follows:
- Lenvatinib 7 days
- TACE 95 days
Refrain from donating sperm
PLUS either:
- Be abstinent from heterosexual intercourse as their preferred and usual
lifestyle and agree to remain abstinent OR
- Must agree to use contraception unless confirmed to be azoospermic.
- Contraceptive use by men should be consistent with local regulations
regarding the methods of contraception for those participating in clinical
studies.
11. 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 the time needed to eliminate each study intervention after the last dose
of study intervention and agrees not to donate eggs (ova, oocytes) to others of
freeze/store for her own use for the purpose of reproduction during this
period. The length of time required to continue contraception for each study
intervention is as follows:
- Pembrolizumab 120 days
- Lenvatinib 30 days
- TACE 180 days
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 within 24 hours
for urine or 72 hours for serum 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.
• Additional requirements for pregnancy testing during and after study
intervention are located in Appendix 2.
• The investigator is respon
1. Has HCC lesion(s) measuring >=10 cm in any dimension, has more than 10
lesions on radiographic evaluation or has HCC lesions occupying >=50% of the
liver volume, confirmed by BICR.
2. Is currently a candidate for liver transplantation.
3. 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 the first dose of
study intervention. 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 intervention are excluded.
4. Has bleeding or thrombotic disorders or is using factor X inhibitors or
anticoagulants requiring therapeutic INR monitoring, eg, warfarin or similar
agents. Treatment with anti-platelet agents and low molecular weight heparin is
permitted.
5. Has clinically apparent ascites on physical examination that is not
controlled with medication.
Note: Ascites detectable on imaging studies only are allowed.
6. Has any macrovascular tumor thrombosis in the portal veins, confirmed by
BICR.
Note: microvascular tumor thrombosis detected on biopsy, but not radiographic
scan, is permitted.
7. 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 excluded.
8. Has medical contraindications that preclude all forms of contrast enhanced
imaging (CT or MRI).
9. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any
other condition that might affect the absorption of lenvatinib.
10. Has a preexisting Grade >=3 gastrointestinal or non-gastrointestinal fistula.
11. Has clinically significant hemoptysis from any source or tumor bleeding
within 2 weeks prior to the first dose of study intervention.
12. Has significant cardiovascular impairment within 12 months of the first
dose of study intervention such as history of congestive heart failure greater
than NYHA Class II (Appendix 12), unstable angina, myocardial infarction or
cerebrovascular accident stroke, or cardiac arrhythmia associated with
hemodynamic instability.
13. Has had major surgery to the liver within 4 weeks prior to the first dose
of study intervention.
Note: If participant underwent major surgery, they must have adequately
recovered from the toxicity and/or complications from the intervention prior to
starting study intervention.
14. Has had a minor surgery (ie, simple excision) within 7 days prior to the
first dose of study intervention (Cycle 1 Day 1).
15. Has serious nonhealing wound, ulcer, or bone fracture.
16. Has HAP score D.
17. Has received any systemic chemotherapy, including anti-VEGF therapy, or any
systemic investigational anticancer agents for HCC.
18. 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 co-inhibitory T-cell
receptor (eg, CTLA-4, OX-40, or CD137).
19. Has received locoregional therapy to liver (such as TACE, transarterial
embolization, TARE, hepatic arterial infusion, or radiation,) for treatment of
H
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>1) PFS per RECIST 1.1 assessed by BICR modified to follow a maximum of 10<br /><br>target lesions and a maximum of 5 target lesions per organ, with new<br /><br>intrahepatic lesions meeting LI-RADS 5 criteria.<br /><br>2) OS</p><br>
- Secondary Outcome Measures
Name Time Method <p>- PFS<br /><br>- OR: CR or PR.<br /><br>- Disease control (DC): a best overall response of complete response (CR),<br /><br>partial response (PR), or stable disease (SD). SD must be achieved at >=6 weeks<br /><br>after randomization to be considered best overall response.<br /><br>- DOR: the time from the first documented evidence of CR or PR until the first<br /><br>documented disease progression or death due to any cause, whichever occurs<br /><br>first.<br /><br>- TTP: the time from randomization to the first documented disease progression<br /><br>- Adverse Events (AEs), serious adverse events (SAEs) and hepatic AEs<br /><br>- Study intervention discontinuations due to AEs<br /><br>- OR, DC, DOR and TTP</p><br>