A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants with RCC (U03): Substudy 03B
- Conditions
- MedDRA version: 20.0Level: LLTClassification code 10038409Term: Renal cell carcinoma NOSSystem Organ Class: 100000004864Renal Cell CarcinomaTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003610-13-HU
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 370
1.Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC (with or without sarcomatoid features)
2.Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a PD-(L)1 checkpoint inhibitor (in sequence or in combination with a VEGF-TKI)
PD-(L)1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria:
-Has received at least 2 doses of an anti-PD-(L)1 mAb
-Has shown radiographic disease progression during or after an anti- PD-(L)1 mAb as defined by RECIST 1.1 by investigator
-Disease progression has been documented within 12 weeks from the last dose of an anti-PD-(L)1 mAb
3.Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a VEGF-TKI (in sequence or in combination with a PD-[L]1 checkpoint inhibitor).
VEGF-TKI treatment progression is defined by meeting the following criterion:
-Has shown radiographic disease progression during or after a treatment with a VEGF-TKI as defined by RECIST 1.1 by investigator
4.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
5.Has a KPS =70% assessed =10 days before to randomization/allocation.
6.Is able to swallow oral medication
7.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
8.Has adequate organ function. Specimens must be collected within 10 days before the start of study intervention
9.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
10.Has resolution of the toxic effect(s) of prior therapy to =Grade 1 (except alopecia or Grade 2 hypothyroidism) and if receiving systemic steroid therapy due to an irAE, the dose should not exceed 10 mg daily of prednisone or equivalent
11.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.
12.Is male or female, from 18 years to 120 years of age inclusive, at the time of signing the informed consent
13.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-4830 – 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)
14.A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applie
1.Has clinically significant cardiovascular diseasewithin 12 months from first dose of study intervention administration, or New York Heart Association Class III or IV congestive heart failure, unstable angina, acute 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. 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 previously received treatment with pembrolizumab plus lenvatinib (in combination)
13. Has received prior treatment with belzutifan or another HIF-2a inhibitor.
14 .Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids
15.Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
16.Has received more than 4 previous systemic anticancer treatment regimens
17.Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
18.Participants who have been previously allocated/randomized to study intervention in any substudy of protocol MK-3475-U03
19.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
20.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
21.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 (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days before first dose of study intervention
22.Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
23.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
24.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 cortico
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