Carcinoma, Renal Cell Clinical Trial
Official title:
A Phase 1b/2 Study of Immune and Targeted Combination Therapies in Participants With RCC (U03): Substudy 03B
| Verified date | January 2024 |
| Source | Merck Sharp & Dohme LLC |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Substudy 03B is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC). The larger study is the umbrella study (U03). The goal of substudy 03B is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with advanced second line plus (2L+) clear cell renal cell carcinoma (ccRCC). This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to demonstrate a tolerable safety profile for the combination of investigational agents. There will be no hypothesis testing in this study.
| Status | Active, not recruiting |
| Enrollment | 370 |
| Est. completion date | September 7, 2025 |
| Est. primary completion date | September 7, 2025 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 120 Years |
| Eligibility | Inclusion Criteria: - Has a histologically confirmed diagnosis of locally advanced/metastatic ccRCC - 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 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 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 - 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. - Is able to swallow oral medication - Has adequate organ function - Participants receiving bone resorptive therapy must have therapy initiated at least 2 weeks before randomization/allocation - Has resolution of toxic effects of prior therapy to =Grade 1 - Has adequately controlled blood pressure (BP =150/90 mm Hg) with no change in hypertensive medications within 1 week before randomization/allocation - 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 - 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 Exclusion Criteria: - 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 - Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention administration - Has had major surgery within 3 weeks before first dose of study interventions - Has a history of lung disease - Has a history of inflammatory bowel disease - Has preexisting gastrointestinal (GI) or non-GI fistula - Has malabsorption due to prior GI surgery or disease - Has previously received treatment with a combination of pembrolizumab plus lenvatinib - Has received prior treatment with belzutifan - Has received prior radiotherapy within 2 weeks of start of study intervention - Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention; killed vaccines are allowed - Has received more than 4 previous systemic anticancer treatment regimens - Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days prior to the first dose of study intervention - Has known additional malignancy that is progressing or has required active treatment within the past 3 years - Has known central nervous system (CNS) metastases and/or carcinomatous meningitis - 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 - Has an active infection requiring systemic therapy - Has a known history of human immunodeficiency virus (HIV) infection - Has a known history of Hepatitis B - Has had an allogenic tissue/solid organ transplant |
| Country | Name | City | State |
|---|---|---|---|
| Australia | Western Sydney Local Health District ( Site 3601) | Blacktown | New South Wales |
| Australia | Royal Brisbane and Women s Hospital ( Site 3603) | Herston | Queensland |
| Australia | St George Hospital ( Site 3602) | Kogarah | New South Wales |
| Australia | Austin Health ( Site 3600) | Melbourne | Victoria |
| Canada | Jewish General Hospital ( Site 3100) | Montreal | Quebec |
| Canada | Princess Margaret Cancer Centre ( Site 3101) | Toronto | Ontario |
| Chile | Bradfordhill-Clinical Area ( Site 4101) | Santiago | Region M. De Santiago |
| Chile | FALP-UIDO ( Site 4100) | Santiago | Region M. De Santiago |
| Chile | CIDO SpA-Oncology ( Site 4106) | Temuco | Araucania |
| Chile | James Lind Centro de Investigación del Cáncer ( Site 4108) | Temuco | Araucania |
| Chile | ONCOCENTRO APYS-ACEREY ( Site 4103) | Viña del Mar | Valparaiso |
| France | Institut de cancérologie Strasbourg Europe (ICANS) ( Site 3203) | Strasbourg | Alsace |
| France | Institut Claudius Regaud ( Site 3200) | Toulouse Cedex 9 | Haute-Garonne |
| France | Institut De Cancerologie De Lorraine ( Site 3204) | Vandoeuvre les Nancy | Ain |
| France | Gustave Roussy ( Site 3202) | Villejuif | Val-de-Marne |
| Hungary | Országos Onkológiai Intézet-Urogenitális Tumorok és Klinikai Farmakológiai Osztály ( Site 4301) | Budapest | Pest |
| Israel | Rambam Health Care Campus-Oncology Division ( Site 3500) | Haifa | |
| Israel | Hadassah Medical Center-Oncology ( Site 3504) | Jerusalem | |
| Israel | Rabin Medical Center ( Site 3502) | Petah Tiqwa | |
| Israel | Sheba Medical Center - Oncology Division ( Site 3501) | Ramat Gan | |
| Israel | Sourasky Medical Center ( Site 3503) | Tel Aviv | |
| Korea, Republic of | Samsung Medical Center ( Site 3801) | Seoul | |
| Korea, Republic of | Severance Hospital ( Site 3802) | Seoul | |
| Korea, Republic of | Asan Medical Center ( Site 3800) | Songpagu | Seoul |
| Netherlands | Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 4402) | Amsterdam | Noord-Holland |
| Netherlands | Erasmus Medisch Centrum ( Site 4401) | Rotterdam | Zuid-Holland |
| New Zealand | Auckland City Hospital ( Site 3700) | Auckland | |
| Poland | Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 4201) | Bydgoszcz | Kujawsko-pomorskie |
| Poland | Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 4202) | Gdansk | Pomorskie |
| Poland | Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Oddzial Badan Wczesnych Faz ( Site 4200 | Warszawa | Mazowieckie |
| Spain | Hospital Universitari Vall d Hebron ( Site 3300) | Barcelona | Cataluna |
| Spain | Hospital Universitario Ramon y Cajal ( Site 3301) | Madrid | |
| United Kingdom | Velindre Cancer Centre Hospital ( Site 3407) | Cardiff | Wales |
| United Kingdom | Western General Hospital ( Site 3402) | Edinburgh | Midlothian |
| United Kingdom | The Beatson West of Scotland Cancer Centre ( Site 3405) | Glasgow | Glasgow City |
| United Kingdom | Leicester Royal Infirmary ( Site 3408) | Leicester | Leicestershire |
| United Kingdom | Barts Health NHS Trust ( Site 3401) | London | London, City Of |
| United Kingdom | The Christie NHS Foundation Trust ( Site 3400) | Manchester | |
| United Kingdom | Royal Preston Hospital ( Site 3406) | Preston | Lancashire |
| United Kingdom | Southampton General Hospital ( Site 3403) | Southampton | England |
| United States | University of Chicago ( Site 3013) | Chicago | Illinois |
| United States | UTSW Medical Center ( Site 3003) | Dallas | Texas |
| United States | Henry Ford Health System ( Site 3014) | Detroit | Michigan |
| United States | Duke Cancer Institute ( Site 3015) | Durham | North Carolina |
| United States | University of Iowa ( Site 3012) | Iowa City | Iowa |
| United States | Vanderbilt University Medical Center ( Site 3004) | Nashville | Tennessee |
| United States | Yale-New Haven Hospital-Yale Cancer Center ( Site 3011) | New Haven | Connecticut |
| United States | Laura and Isaac Perlmutter Cancer Center ( Site 3016) | New York | New York |
| United States | Memorial Sloan Kettering Cancer Center ( Site 3002) | New York | New York |
| United States | UPMC Cancer Center/Hillman Cancer Center ( Site 3017) | Pittsburgh | Pennsylvania |
| United States | University of California at San Francisco ( Site 3008) | San Francisco | California |
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme LLC |
United States, Australia, Canada, Chile, France, Hungary, Israel, Korea, Republic of, Netherlands, New Zealand, Poland, Spain, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Safety Lead-in Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs) | DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting =3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the safety lead-in phase will be presented. | Up to ~21 days | |
| Primary | Safety Lead-in Phase: Number of participants who experience one or more adverse events (AEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs in the safety lead-in phase will be presented. | Up to ~21 days | |
| Primary | Safety Lead-in Phase: Number of participants who discontinue study treatment due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE in the safety lead-in phase will be presented. | Up to ~21 days | |
| Primary | Efficacy Phase: Number of participants who experienced DLTs | DLTs are defined as one or more of the following toxicities: (1) grade (gr) 4 nonhematologic toxicity (2) gr 4 hematologic toxicity lasting >7 days OR gr 4 platelet count decreased of any duration OR gr 3 platelet count decreased if associated with bleeding (3) gr 3 nonhematologic toxicity except gr 3 fatigue (lasting =3 days), diarrhea, nausea, vomiting or rash without standard of care (4) gr 3 or 4 nonhematologic abnormality if medical intervention is required or if it leads to hospitalization or persists for >1 week (5) gr 3 or 4 febrile neutropenia (6) gr 3 or 4 alanine aminotransferase, aspartate aminotransferase and/or bilirubin laboratory value (7) treatment related adverse event (AE) causing study intervention discontinuation during the first 21 days (8) treatment related AE causing intervention administration delay for >14 days during the first 21 days (9) gr 5 toxicity. The number of participants who experience one or more DLTs in the efficacy phase will be presented. | Up to ~21 days | |
| Primary | Efficacy Phase: Number of participants who experience one or more AEs | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience one or more AEs in the efficacy phase will be presented. | Up to ~56 months | |
| Primary | Efficacy Phase: Number of participants who discontinue study treatment due to an AE | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study treatment due to an AE in the efficacy phase will be presented. | Up to ~56 months | |
| Primary | Efficacy Phase: Objective response rate (ORR) | ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR). | Up to ~56 months | |
| Secondary | Efficacy Phase: Duration of response (DOR) | For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR. | Up to ~56 months | |
| Secondary | Efficacy Phase: Progression-free survival (PFS) | PFS is defined as the time from randomization to the first documented progressive disease or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 by BICR. | Up to ~56 months | |
| Secondary | Efficacy Phase: Overall survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to ~56 months | |
| Secondary | Efficacy Phase: Clinical benefit rate (CBR) | CBR is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) of =6 months. Responses are according to RECIST 1.1 by BICR. | Up to ~56 months |
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