A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants with RCC (U03): Substudy 03B
- Conditions
- Renal Cell CarcinomaMedDRA version: 20.0Level: LLTClassification code 10038409Term: Renal cell carcinoma NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003610-13-FR
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- 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 demonstrated 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 demonstrated 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 demonstrated in such lesions
5.Has a KPS =70% assessed =10 days prior 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 prior to 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 prior to randomization/allocation
10.Has resolution of the toxic effect(s) of the most recent 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.If participants received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention
12.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 prior to randomization/allocation.
13.Is male or female, from 18 years to 120 years of age inclusive, at the time of signing the informed consent
14.Male participants are eligible to participate if they agree to the following during treatment with and for at least 5 days after the last dose of lenvatinib and/or MK-6482:
-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) 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 c
1.Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 12 months from Day 1 of study intervention administration, or New York Heart Association Class III or IV congestive heart failure, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability. Medically controlled arrhythmia stable on medication is permitted
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 prior to 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 following 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.Has previously received treatment with pembrolizumab plus lenvatinib (in combination)
12. Has received prior treatment with MK-6482 or another HIF-2a inhibitor.
13 .Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease
14.Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
15.Has received more than 4 previous systemic anticancer treatment regimens
16.Is currently participating in a study of an investigational agent or is currently using an investigational device
17.Participants who have been previously allocated/randomized to study intervention in any substudy of protocol MK-3475-U03
18.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
19.Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
20.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 prior to first dose of study intervention
21.Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
22.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
23.Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modi
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