A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants with RCC (U03): Substudy 03A
- Conditions
- Renal Cell CarcinomaMedDRA version: 26.0Level: LLTClassification code 10038409Term: Renal cell carcinoma NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003609-84-NL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 430
1. Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC (with or without sarcomatoid features), ie, Stage IV RCC per AJCC
2. Has received no prior systemic therapy for advanced RCC. [1L participants]
3. Has measurable disease per RECIST 1.1 as assessed by BICR. Lesions situated in a previously irradiated area are considered measurable if progression has been shown in such lesions
4. Has a KPS =70% assessed =10 days before randomization/allocation.
5. Is able to swallow oral medication
6. Submits an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
7. Has adequate organ function. Specimens must be collected within 10 days before the start of study intervention
8. Participants receiving bone resorptive therapy (including but not limited to bisphosphonate or RANK-L inhibitor) must have therapy initiated at least 2 weeks before randomization/allocation
9. Has adequately controlled BP with or without antihypertensive medications, defined as BP =150/90 mm Hg with no change in antihypertensive medications within 1 week before randomization/allocation
10. Is male or female, from 18 years to 120 years of age inclusive, at the time of signing the informed consent
11. 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, belzutifan – 7 days
- Pembrolizumab, MK-1308A, MK-4280A, MK-7684A– no male contraception measures are required
- 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) documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant
- Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
12. 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 :
- uses 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. The length of time required to continue contraception for each study intervention is as follows:
- Lenvatinib, belzutifan – 30 days
- Pembrolizumab, MK-1308A, MK-4280A, MK-7684A – 120 days
The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of s
1. Has clinically significant cardiavasculair disease, within 12 months from first dose of study intervention,including or New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.
2. Prolongation of QTcF interval to >480 ms
3. Has a LVEF below the institutional (or local laboratory) normal range as determined by MUGA or ECHO
4. Has had major surgery within 3 weeks before first dose of study interventions
5. Has urine protein =1 g/24 hours
6. Has a history of interstitial lung disease, history of (non-infectious) pneumonitis that required steroids, or has current pneumonitis
7. 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
8. Has a history of inflammatory bowel disease
9. Has preexisting =Grade 3 GI or non-GI fistula
10. Has malabsorption due to prior GI surgery or GI disease
11. Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study intervention.
12. Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation related toxicities requiring corticosteroids
13. Has received a live or live attenuated vaccine within 30 days before the first dose of study drug.
14. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
15. Have been previously allocated/randomized to study intervention in any substudy of protocol MK-3475-U03
16. 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 drug
17. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
18. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
19. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
20. Has a history of hypersensitivity reaction to any of the investigational agent(s) included in this study. For example, but not limited to:
- Has a severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients
- Has a history of severe hypersensitivity reaction (eg, generalized rash/erythema, hypotension, bronchospasm, angioedema, or anaphylaxis) to lenvatinib
21. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
22. Has an active infection requiring systemic therapy
23. Has a known history of HIV infection. No HIV testing is required unless mandated by local hea
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