An Open-label, Randomized, Phase 3 Study of MK-6482 in Combination with Lenvatinib (MK-7902) vs Cabozantinib for Treatment in Participants with Advanced Renal Cell Carcinoma Who Have Progressed After Prior Anti-PD-1/L1 Therapy
- Conditions
- renal cell cancer10038430
- Registration Number
- NL-OMON52328
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
1. Must have a histologically confirmed diagnosis of unresectable, locally
advanced/metastatic RCC with clear cell component (with or without
sarcomatoid features) ie, Stage IV RCC per AJCC (8th Edition). Previous
nephrectomy or metastasectomy is allowed.
2. Has experienced disease progression on or after an anti-PD-1/L1 therapy as
either first- or second-line treatment for locally advanced/metastatic RCC or
as adjuvant or neoadjuvant/adjuvant treatment with progression on or within 6
months of last dose. The anti-PD-1/L1 therapy may have been monotherapy or in
combination with other agent(s) such as anti- CTLA4 or VEGFtargeted-
TKI. The immediately preceding line of treatment has to have been an
anti-PD-1/L1 therapy.
- Treatment progression is defined by meeting ALL of the following criteria:
o Has received at least 2 doses of an anti-PD-1/L1 mAb.
o Has shown radiographic disease progression during or after an anti-PD-1/L1
mAb as assessed by investigator.
3. Has measurable disease per RECIST 1.1 as assessed by the local site
investigator/radiology. Lesions situated in a previously irradiated area
are considered measurable if progression has been shown in such lesions.
4. Has a KPS >=70% assessed within 10 days before randomization.
5. Has received no more than 2 prior systemic regimens including:
- One anti-PD-1/L1 containing adjuvant or neoadjuvant/adjuvant regimens with
progression on or within 6 months from the last dose of that regimen
OR
-One or 2 regimens for locoregional/advanced disease
6. Has received only 1 prior anti-PD-1/L1 therapy for adjuvant,
neoadjuvant/adjuvant or locally advanced/metastatic RCC.
7. Has recovered from all AEs due to previous therapies to <=Grade 1 or
baseline. Participants with <=Grade 2 neuropathy may be eligible.
Participants with endocrine-related AEs Grade <=2 requiring treatment or hormone
replacement may be eligible.
8. If participants received major surgery or radiation therapy of >30 Gy, they
must have recovered from the toxicity and/or complications from
the intervention.
9. Is male or female, at least 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 7 days after the
last dose of belzutifan or lenvatinib in the belzutifan+lenvatinib arm,
whichever occurs last, and 23 days after the last dose of cabozantinib:
• 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.
-If the contraception requirements in the local label for any of the study
interventions is more stringent than the requirements above, the local
label requirements are to be followed.
11. A female participant is eligible to participate if they are not pregnant or
breastfeeding, and at least 1 of the following conditions applies:
• Is not a WOCBP.
OR
• Is a WOCBP and using a contraceptive method that is highly effective during
the treatment period and for at least 120 days after the last dose
of cabozantinib for participants in th
1. A WOCBP who has a positive urine pregnancy test within 24 hours before first
dose of study intervention. If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required.
2. Has any of the following:
- A pulse oximeter reading <92% at rest, or
- Requires intermittent supplemental oxygen, or
- Requires chronic supplemental oxygen.
3. Has a known additional malignancy that is progressing or has required active
treatment within the past 3 years.
4. Has known CNS metastases and/or carcinomatous meningitis.
5. Has clinically significant cardiovascular disease within 12 months from
first dose of study intervention, including but not limited to New York Heart
Association
Class III or IV congestive heart failure, unstable angina, myocardial
infarction, cerebral vascular accident, or cardiac arrhythmia.
6. Prolongation of QTc interval to >480 ms.
7. Has a LVEF below the institutional (or local laboratory) normal range as
determined by MUGA or ECHO.
8. Has urine protein >=1 g/24 hours.
9. Has symptomatic pleural effusion (for example cough, dyspnea, pleuritic
chest pain). A participant who is clinically stable after treatment
for these conditions (including therapeutic thoraco- or paracentesis) is
eligible.
10. Has pre-existing >=Grade 3 gastrointestinal or nongastrointestinal fistula.
11. Has moderate to severe hepatic impairment (Child-Pugh B or C).
12. Has clinically significant hematuria, hematemesis or hemoptysis (>2.5 ml)
of red blood, or other history of significant bleeding (eg,
pulmonary hemorrhage) within 3 months before randomization.
13. Has other clinically significant disorders such as:
a. Serious active nonhealing wound/ulcer/bone fracture
b. Requirement for hemodialysis or peritoneal dialysis
c. History of solid organ transplantation
14. Received colony-stimulating factors (eg, G-CSF, GMCSF or recombinant EPO)
within 28 days before randomization.
15. Has a known psychiatric or substance abuse disorder that would interfere
with cooperation with the requirements of the study.
16. Is unable to swallow orally administered medication or has a
gastrointestinal disorder affecting absorption (eg, gastrectomy, partial
bowel obstruction, malabsorption).
17. Has known hypersensitivity or allergy to the active pharmaceutical
ingredient or any component of the study intervention (belzutifan,
lenvatinib, or cabozantinib) formulations.
18. Has received prior treatment with belzutifan or another HIF-2a inhibitor.
19. Has received prior treatment with lenvatinib.
20. Has received prior treatment with cabozantinib.
21. Has received any type of small molecule kinase inhibitor (including
investigational kinase inhibitor) within 2 weeks before randomization.
22. Has received any type of systemic anticancer antibody (including
investigational antibody) <=28 days before randomization.
23. Has received prior radiotherapy within 2 weeks before randomization.
Participants must have recovered from all radiationrelated
toxicities and not require corticosteroids. A 1-week washout is required for
palliative radiation (<=2 weeks of radiotherapy) to non-CNS
disease.
24. Has had major surgery within 3 weeks before randomization.
25. Is receiving concomitant treatment, in therapeutic doses, with
anticoagulants such as heparin, thrombi
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>PFS: the time from randomization to the first documented disease progression or<br /><br>death due to any cause, whichever occurs first.<br /><br>OS: the time from randomization to death due to any cause.</p><br>
- Secondary Outcome Measures
Name Time Method <p>- Objective response (OR): complete response (CR) or partial response (PR).<br /><br>- DOR: the time from first documented evidence of CR or PR until either disease<br /><br>progression or death due to any cause, whichever occurs first.<br /><br>- Adverse events (AEs).<br /><br>- Study intervention discontinuation due to AEs.</p><br>