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)

Study Purpose

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.

Arm 1: Pembrolizumab + Vibostolimab was added in the base protocol on 13-Nov-2019, and enrollment into this arm has been completed. Arm 2: Pembrolizumab was added in the base protocol on 13-Nov-2019, and enrollment stopped prematurely on 15-Aug-2022. Arm 3: Coformulation Pembrolizumab/Quavonlimab was added in Amendment 01 on 20-Oct-2020, and enrollment stopped prematurely on 15-Aug-2022. Arm 4: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib was added in Amendment 01 on 20-Oct-2020, and enrollment is ongoing. Arm 5: Coformulation Favezelimab/Pembrolizumab was added in Amendment 03 on 01-DEC-2022 and has paused enrollment, Arm 6: Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA) was added in Amendment 03 on 01-DEC-2022 and has paused enrollment, and Arm 7: Coformulation Favezelimab/Pembrolizumab + Vibostolimab was added in Amendment 03 on 01-DEC-2022 and enrollment was stopped prematurely on 22-SEP-2023.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

Inclusion Criteria:

- Has histologically or cytologically confirmed melanoma.

- Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy.

- Has been untreated for advanced disease.

- Has provided a tumor biopsy.

- 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.

- 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.

- Has adequate organ function.

- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)
Exclusion Criteria:
- 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 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 history of Hepatitis B or known Hepatitis C virus infection.

- 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 known psychiatric or substance abuse disorder that would interfere with requirements of the study.

- 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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04305054
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 1/Phase 2
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Merck Sharp & Dohme LLC
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Medical Director
Principal Investigator Affiliation	Merck Sharp & Dohme LLC
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Chile, Colombia, France, Greece, Hungary, Israel, Italy, Poland, South Africa, Spain, Switzerland, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Melanoma
Study Website:	View Trial Website

Additional Details

With Amendment 5, participants receiving vibostolimab (Arm 1 and Arm 7) will discontinue treatment with vibostolimab and will be transitioned within their arm to pembrolizumab monotherapy. Participants receiving favezelimab (Arm 5, Arm 6, and Arm 7) may continue on study therapy until the end of study or may transition within their arm to pembrolizumab monotherapy. Participants with access to approved standard of care (SOC, pembrolizumab plus chemotherapy) should be considered for discontinuation from the study. Those benefiting from pembrolizumab with chemotherapy, but unable to access it as SOC outside the study, may continue on study and receive treatment with pembrolizumab plus chemotherapy until discontinuation criteria are met.

Arms & Interventions

Arms

Experimental: Pembrolizumab + 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.

Active Comparator: Pembrolizumab

Participants will receive pembrolizumab IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.

Experimental: Coformulation 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.

Experimental: Coformulation Pembrolizumab/Quavonlimab + 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.

Experimental: Coformulation 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

Experimental: Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (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).

Experimental: Coformulation Favezelimab/Pembrolizumab + 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.

Interventions

Biological: - Pembrolizumab

Administered via IV infusion at a specified dose on specified days

Biological: - Vibostolimab

Administered via IV infusion at a specified dose on specified days

Biological: - Pembrolizumab/Quavonlimab

Administered via IV infusion at a specified dose on specified days

Drug: - Lenvatinib

Administered via oral capsule at a specified dose on specified days

Biological: - Favezelimab/Pembrolizumab

Administered via IV infusion at a specified dose on specified days

Drug: - ATRA

Administered via oral capsule at a specified dose on specified days

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Los Angeles, California

Status

Recruiting

Address

The Angeles Clinic and Research Institute ( Site 2009)

Los Angeles, California, 90025

Site Contact

Study Coordinator

Cookie Policy

Main Menu

Clinical Trial Finder