Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02)
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT04305054
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Substudy 02B is part of a larger research study where researchers are looking for new ways to treat advanced melanoma that has not been treated before. The larger study is the umbrella study. Researchers want to know if adding other treatments to pembrolizumab can treat advanced melanoma. The goals of this study are to learn:
* About the safety and how well people tolerate pembrolizumab given with other treatments
* How many people have melanoma that responds (gets smaller or goes away) to treatment
- Detailed Description
With Amendment 6, all arms are closed to enrollment. Participants in arms 2 (pembrolizumab), 3 (coformulation pembrolizumab/quavonlimab), and 4 (coformulation pembrolizumab/quavonlimab + lenvatinib) who complete study treatment or otherwise meet end of treatment (EOT) criteria will be discontinued from the study after completing the EOT visit and any required safety follow-up visits. Participants in arm 6 (coformulation favezelimab/pembrolizumab + All-trans Retinoic Acid \[ATRA\]) will discontinue ATRA and participants in arms 5 and 6 can continue on coformulation favezelimab/pembrolizumab or pembrolizumab.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 315
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Has histologically or cytologically confirmed melanoma
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Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
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Has been untreated for advanced disease.
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Has provided a tumor biopsy
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If capable of producing sperm, male participants 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 (7 days):
- Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
- Uses contraception unless confirmed to be azoospermic
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A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:
- Is not a WOCBP OR
- Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) 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:
- MK-4280A: 120 days
- MK-1308A: 120 days
- MK-7684: 50 days
- MK-3475: 120 days
- Lenvatinib: 30 days
- ATRA: 30 days
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Has adequate organ function
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Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)
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Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
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Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
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Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
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Has ocular or mucosal melanoma
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Has an active autoimmune disease that has required systemic treatment in the past 2 years
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Has an active infection requiring systemic therapy
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Has known history of human immunodeficiency virus (HIV)
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Has history of Hepatitis B or known Hepatitis C virus infection
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Has a history of (noninfectious) pneumonitis
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Has a history of active tuberculosis (TB)
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Has received prior systemic anticancer therapy within 4 weeks prior to randomization
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Has received prior radiotherapy within 2 weeks of first dose of study intervention
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Has had major surgery <3 weeks prior to first dose of study intervention
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Has received a live vaccine within 30 days before the first dose of study intervention
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Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
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Has had an allogeneic tissue/solid organ transplant
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Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
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Participants who receive lenvatinib have the following additional exclusion criteria:
- Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula
- Has radiographic evidence of encasement of invasion of a 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
- Has urine protein ≥1 g/24-hour.
- Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab Pembrolizumab Participants will receive pembrolizumab IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years. Coformulation Pembrolizumab/Quavonlimab Pembrolizumab Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years. Coformulation Pembrolizumab/Quavonlimab Pembrolizumab/Quavonlimab Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years. Pembrolizumab + Vibostolimab Vibostolimab Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years. Coformulation Favezelimab/Pembrolizumab Favezelimab/Pembrolizumab Participants will receive cofomulation of favezelimab + pembrolizumab (MK-4280A) IV at specified dose on specified days every 3 weeks (Q3W) for up to approximately 2 years Coformulation Favezelimab/Pembrolizumab + Vibostolimab Vibostolimab Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years. Coformulation Favezelimab/Pembrolizumab + Vibostolimab Favezelimab/Pembrolizumab Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years. Coformulation Pembrolizumab/Quavonlimab + Lenvatinib Pembrolizumab/Quavonlimab Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years. Pembrolizumab + Vibostolimab Pembrolizumab Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years. Coformulation Pembrolizumab/Quavonlimab + Lenvatinib Pembrolizumab Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years. Coformulation Pembrolizumab/Quavonlimab + Lenvatinib Lenvatinib Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years. Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA) ATRA Participants will receive coformulation of favezelimab and pembrolizumab IV Q3W for up to 35 cycles, plus ATRA orally (for 3 days surrounding each infusion of MK-4280A, including Days 1, 2, and 3 of Cycle 1 and on Days -1, 1, and 2 of all subsequent cycles).
- Primary Outcome Measures
Name Time Method Percentage of participants who experience a dose-limiting toxicity (DLT): Safety lead-in phase Up to ~3 weeks The percentage of participants who experience 1 or more protocol-defined DLTs during the safety lead-in period will be reported.
Percentage of participants who experience an adverse event (AE): Safety lead-in Up to ~3 weeks 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 during the safety lead-in period will be reported.
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.
Percentage of participants who discontinue study treatment due to an AE: Safety lead-in Up to ~3 weeks 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 during the safety lead-in will be reported.
- 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 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 (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 (60)
The Angeles Clinic and Research Institute ( Site 2009)
🇺🇸Los Angeles, California, United States
UCLA Hematology & Oncology ( Site 2004)
🇺🇸Los Angeles, California, United States
Providence Saint John's Health Center ( Site 2010)
🇺🇸Santa Monica, California, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 2012)
🇺🇸Aurora, Colorado, United States
University of Florida College of Medicine-UF Health Cancer Center/Clinical Trials Office ( Site 2026)
🇺🇸Gainesville, Florida, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 2022)
🇺🇸Baltimore, Maryland, United States
R.J. Zuckerberg Cancer Center ( Site 2032)
🇺🇸Lake Success, New York, United States
NYU Clinical Cancer Center ( Site 2002)
🇺🇸New York, New York, United States
Duke Cancer Institute ( Site 2005)
🇺🇸Durham, North Carolina, United States
Martha Morehouse Tower ( Site 2020)
🇺🇸Columbus, Ohio, United States
Scroll for more (50 remaining)The Angeles Clinic and Research Institute ( Site 2009)🇺🇸Los Angeles, California, United States