MK-4830 for Renal cell carcinoma

Inclusion criteria

• {"criterion_text":"- Has a histologically confirmed diagnosis of locally advanced/metastatic clear cell renal cell carcinoma (ccRCC)"}
• {"criterion_text":"- Female participant is not pregnant or breastfeeding and is not a woman of childbearing potential (WOCBP) or is a WOCBP abstinent from heterosexual intercourse or using contraception during the intervention period and for at least 120 days after the last dose of pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, MK-4830 or 30 days after the last dose of lenvatinib or belzutifan, whichever occurs last and must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention"}
• {"criterion_text":"- Has experienced disease progression on or after having received systemic treatment for locally advanced or metastatic RCC with a programmed cell death ligand 1 (PD-(L)1) checkpoint inhibitor (in sequence or in combination with a vascular endothelial growth factor tyrosine kinase inhibitor [VEGF-TKI]) where PD-(L)1 checkpoint inhibitor treatment progression is defined by meeting ALL of the following criteria: (a) has received ≥2 doses of an anti-PD-(L)1 monoclonal antibody (mAb) (b) has shown radiographic disease progression during or after an anti-PD-(L)1 mAb as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by investigator (c) disease progression has been documented within 12 weeks from the last dose of an anti-PD-(L)1 mAb"}
• {"criterion_text":"- 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) where 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"}
• {"criterion_text":"- Is able to swallow oral medication"}
• {"criterion_text":"- Has adequate organ function"}
• {"criterion_text":"- Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation"}
• {"criterion_text":"- Has resolution of toxic effects of prior therapy to ≤Grade 1"}
• {"criterion_text":"- Has adequately controlled blood pressure (BP ≤150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation"}
• {"criterion_text":"- Male participants are abstinent from heterosexual intercourse or agree to use contraception during treatment with and for at least 7 days after the last dose of lenvatinib and /or belzutifan; 7 days after lenvatinib and/or belzutifan is stopped, if the participant is only receiving pembrolizumab, pembrolizumab/quavonlimab, favezelimab/pembrolizumab, MK-4830 or a combination of the aforementioned drugs, no contraception is needed"}

Exclusion criteria

• {"criterion_text":"- Has urine protein ≥1 g/24 hours and has any of the following: (a) a pulse oximeter reading <92% at rest, or (b) requires intermittent supplemental oxygen, or (c) requires chronic supplemental oxygen (d) active hemoptysis within 3 weeks prior to the first dose of study intervention"}
• {"criterion_text":"- Has received prior radiotherapy within 2 weeks of start of study intervention"}
• {"criterion_text":"- Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention; killed vaccines are allowed"}
• {"criterion_text":"- Has received more than 4 previous systemic anticancer treatment regimens"}
• {"criterion_text":"- Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention"}
• {"criterion_text":"- Has known additional malignancy that is progressing or has required active treatment within the past 3 years"}
• {"criterion_text":"- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis"}
• {"criterion_text":"- Has an active autoimmune disease that has required systemic treatment in the past 2 years; replacement therapy is not considered a form of systemic treatment and is allowed"}
• {"criterion_text":"- Has an active infection requiring systemic therapy"}
• {"criterion_text":"- Has a known history of human immunodeficiency virus (HIV) infection"}
• {"criterion_text":"- Has a known history of Hepatitis B"}
• {"criterion_text":"- Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration"}
• {"criterion_text":"- Has had an allogenic tissue/solid organ transplant"}
• {"criterion_text":"- Has had major surgery within 3 weeks before first dose of study interventions"}
• {"criterion_text":"- Has a history of lung disease"}
• {"criterion_text":"- Has a history of inflammatory bowel disease"}
• {"criterion_text":"- Has preexisting gastrointestinal (GI) or non-GI fistula"}
• {"criterion_text":"- Has malabsorption due to prior GI surgery or disease"}
• {"criterion_text":"- Has previously received treatment with a combination of pembrolizumab plus lenvatinib"}
• {"criterion_text":"- Has received prior treatment with belzutifan"}

Primary endpoints

• {"endpoint_text":"- Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)","definition_or_measurement_approach":"Count of participants experiencing one or more DLTs during the safety lead-in phase (DLT definition not provided in the CTIS excerpt)"}
• {"endpoint_text":"- Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs)","definition_or_measurement_approach":"Count of participants with one or more adverse events (AEs)"}
• {"endpoint_text":"- Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE","definition_or_measurement_approach":"Count of participants who discontinue study treatment due to an AE"}
• {"endpoint_text":"- Efficacy Phase: Number of participants who experienced DLTs","definition_or_measurement_approach":"Count of participants who experienced DLTs during the efficacy phase"}
• {"endpoint_text":"- Efficacy Phase: Number of participants who experience one or more AEs","definition_or_measurement_approach":"Count of participants with one or more adverse events during the efficacy phase"}
• {"endpoint_text":"- Efficacy Phase: Number of participants who discontinue study treatment due to an AE","definition_or_measurement_approach":"Count of participants who discontinue study treatment due to an AE during the efficacy phase"}
• {"endpoint_text":"- Efficacy Phase: Objective response (OR)","definition_or_measurement_approach":"Objective response assessed per RECIST 1.1"}

Secondary endpoints

• {"endpoint_text":"- Efficacy Phase: Duration of response (DOR)","definition_or_measurement_approach":"DOR assessed per RECIST 1.1"}
• {"endpoint_text":"- Efficacy Phase: Progression-free survival (PFS)","definition_or_measurement_approach":"PFS assessed per RECIST 1.1"}
• {"endpoint_text":"- Efficacy Phase: Overall survival (OS)","definition_or_measurement_approach":"Overall survival measured as time from baseline to death from any cause"}
• {"endpoint_text":"- Efficacy Phase: Clinical benefit rate (CBR)","definition_or_measurement_approach":"Clinical benefit rate assessed per RECIST 1.1"}

Netherlands

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

06-11-2024

Processing Time Days

292

Number Of Sites

3

Number Of Participants

3

Poland

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

12-05-2025

Processing Time Days

479

Number Of Sites

3

Number Of Participants

10

Hungary

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

08-05-2025

Processing Time Days

475

Number Of Sites

1

Number Of Participants

9

Spain

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

26-11-2025

Processing Time Days

677

Number Of Sites

2

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

19-01-2024

Latest Decision Or Authorization Date

06-05-2026

Processing Time Days

838

Number Of Sites

4

Number Of Participants

38

Primary sponsor

Full Name

Merck Sharp & Dohme LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Almac Clinical Technologies LLC

Responsibilities

sponsorDuties code 3

Name

PPD Global Central Labs

Responsibilities

sponsorDuties code 4

Name

Parexel International Corp.

Responsibilities

EUB services (call center and medical services)

Name

PRA International

Responsibilities

Central imaging

Third parties

• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"sponsorDuties code 3","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"sponsorDuties code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Parexel International Corp.","duties_or_roles":"EUB services (call center and medical services)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PRA International","duties_or_roles":"Central imaging","organisation_type":"Pharmaceutical company"}