Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/KEYMAKER-U02)
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT04305041
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Substudy 02A is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study.
The goal of substudy 02A is to evaluate the safety and efficacy of investigational treatment arms in participants with PD-1 refractory melanoma to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September 2021.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 200
- Has histologically or cytologically confirmed melanoma
- Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
- Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy, or in combination with other therapies
- Has imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in the setting of rapid progression.
- Has not received more than 3 lines of therapy for their advanced melanoma
- Has provided a tumor biopsy
- Male participants who receive lenvatinib or ATRA are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of lenvatinib or ATRA; for male participants who only receive pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception measures are needed
- Female participant are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab, quavonlimab, vibostolimab or 30 days after the last dose of lenvatinib or ATRA, whichever occurs last
- Has adequate organ function
- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)
- Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
- Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has ocular or mucosal melanoma
- Has known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another mAb
- Has an active autoimmune disease that has required systemic treatment in the past 2 years
- Has an active infection requiring systemic therapy
- Has known history of human immunodeficiency virus (HIV)
- Has known history of hepatitis B
- Has a history of (noninfectious) pneumonitis
- Has a history of active tuberculosis (TB)
- Has received prior systemic anticancer therapy within 4 weeks prior to randomization
- Has received prior radiotherapy within 2 weeks of first dose of study intervention
- Has had major surgery <3 weeks prior to first dose of study intervention
- Has received a live vaccine within 30 days before the first dose of study intervention
- Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
- Has had an allogeneic tissue/solid organ transplant
- Has a pre-existing Grade ≥3 gastrointestinal fistula or nongastrointestinal fistula
- Has radiographic evidence of encasement of invasion of major blood vessel or of intratumoral cavitation
- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention
- Has clinically significant cardiovascular disease within 12 months from first dose of study intervention
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Quavonlimab + Lenvatinib Pembrolizumab Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years. Pembrolizumab + Quavonlimab + Lenvatinib Quavonlimab Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years. Pembrolizumab + Quavonlimab + Vibostolimab Pembrolizumab Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years. Pembrolizumab + Quavonlimab + Vibostolimab Vibostolimab Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years. Pembrolizumab + Quavonlimab + Lenvatinib Lenvatinib Participants will receive pembrolizumab IV plus quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years. Pembrolizumab + all-trans retinoic acid (ATRA) ATRA Participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days for a total treatment duration of up to approximately 2 years Pembrolizumab + Quavonlimab + Vibostolimab Quavonlimab Participants will receive pembrolizumab intravenously (IV) plus quavonlimab IV plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.
- Primary Outcome Measures
Name Time Method Percentage of participants who experience an adverse event (AE) Up to ~28 months 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 percentage of participants who experience an AE will be reported.
Percentage of participants who discontinue study treatment due to an AE Up to ~24 months 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 percentage of participants who discontinue study treatment due to an AE will be reported.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) Up to ~30 months 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 RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) per RECIST 1.1 Up to ~30 months For participants in the analysis population who show 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 (PD) or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Trial Locations
- Locations (35)
Chaim Sheba Medical Center ( Site 1701)
🇮🇱Ramat Gan, Israel
A.P.H. Paris, Hopital Saint Louis ( Site 1107)
🇫🇷Paris, France
Hopital Saint Andre ( Site 1108)
🇫🇷Bordeaux, Gironde, France
Rambam Health Care Campus-Oncology ( Site 1704)
🇮🇱Haifa, Israel
West Cancer Center - East Campus ( Site 1014)
🇺🇸Germantown, Tennessee, United States
Tasman Oncology Research Pty Ltd ( Site 1403)
🇦🇺Southport, Queensland, Australia
Institut Claudius Regaud ( Site 1105)
🇫🇷Toulouse cedex 9, Haute-Garonne, France
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 1399)
🇮🇹Milano, Italy
Policlinico Le Scotte - A.O. Senese ( Site 1377)
🇮🇹Siena, Italy
NYU Clinical Cancer Center ( Site 1002)
🇺🇸New York, New York, United States
Gustave Roussy ( Site 1101)
🇫🇷Villejuif, Ile-de-France, France
Hadassah Ein Karem Jerusalem ( Site 1702)
🇮🇱Jerusalem, Israel
Hopital La Timone ( Site 1103)
🇫🇷Marseille, Bouches-du-Rhone, France
Centre Hospitalier Lyon Sud ( Site 1102)
🇫🇷Pierre Benite, Rhone, France
HaEmek Medical Center ( Site 1703)
🇮🇱Afula, Israel
Calvary Mater Newcastle-Medical Oncology ( Site 1404)
🇦🇺Waratah, New South Wales, Australia
University of Texas MD Anderson Cancer Center ( Site 1006)
🇺🇸Houston, Texas, United States
Inova Schar Cancer Institute ( Site 1011)
🇺🇸Fairfax, Virginia, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 1022)
🇺🇸Baltimore, Maryland, United States
The Angeles Clinic and Research Institute ( Site 1009)
🇺🇸Los Angeles, California, United States
Melanoma Institute Australia ( Site 1402)
🇦🇺Wollstonecraft, New South Wales, Australia
Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 1603)
🇨🇭Genève, Geneve, Switzerland
CHUV Centre Hospitalier Universitaire Vaudois ( Site 1602)
🇨🇭Lausanne, Vaud, Switzerland
Fiona Stanley Hospital ( Site 1401)
🇦🇺Murdoch, Western Australia, Australia
UCLA Hematology & Oncology ( Site 1004)
🇺🇸Los Angeles, California, United States
Providence Saint John's Health Center ( Site 1010)
🇺🇸Santa Monica, California, United States
Martha Morehouse Tower ( Site 1020)
🇺🇸Columbus, Ohio, United States
University of Pennsylvania Abramson Cancer Center ( Site 1008)
🇺🇸Philadelphia, Pennsylvania, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 1012)
🇺🇸Aurora, Colorado, United States
Duke Cancer Institute ( Site 1005)
🇺🇸Durham, North Carolina, United States
Oregon Health & Science University ( Site 1013)
🇺🇸Portland, Oregon, United States
Istituto Nazionale Tumori Fondazione Pascale ( Site 1302)
🇮🇹Napoli, Italy
Universitaetsspital Zuerich ( Site 1601)
🇨🇭Zuerich Flughafen, Zurich, Switzerland
Istituto Europeo di Oncologia ( Site 1301)
🇮🇹Milano, Italy
Istituto Oncologico Veneto IRCCS ( Site 1355)
🇮🇹Padova, Italy