Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02)
NCT ID: NCT04303169
Last Updated: 2025-10-27
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1/PHASE2
146 participants
INTERVENTIONAL
2020-06-26
2025-09-24
Brief Summary
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The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.
Arm 1: Pembrolizumab + Vibostolimab, Arm 2: Pembrolizumab + Gebasaxturev, and Arm 3: Pembrolizumab were added in the base protocol on 13-Nov-2019, and enrollment into those arms has been completed. Arm 4: Pembrolizumab + MK-4830 was added in Amendment 04 on 20-Dec-2021, and enrollment into that arm has been completed. Arm 5: Favezelimab + Pembrolizumab and Arm 6: Pembrolizumab + all-trans retinoic acid (ATRA) were added in Amendment 06 on 25-Jun-2022, and enrollment is ongoing.
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Detailed Description
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Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Pembrolizumab + Vibostolimab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Vibostolimab
Administered via IV infusion at a specified dose on specified days
Pembrolizumab + Gebasaxturev
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus gebasaxturev (V937) intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Gebasaxturev
Administered via IT injection at a specified dose on specified days
Pembrolizumab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Pembrolizumab + MK-4830
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus MK-4830 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
Pembrolizumab
Administered via IV infusion at a specified dose on specified days
MK-4830
Administered via IV infusion at a specified dose on specified days
Favezelimab + Pembrolizumab
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive MK-4280A (favezelimab and pembrolizumab administered as a co-formulation) IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
Favezelimab + Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Pembrolizumab + all-trans retinoic acid (ATRA)
Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.
Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.
Pembrolizumab
Administered via IV infusion at a specified dose on specified days
ATRA
Administered via oral capsules at a specified dose on specified days
Interventions
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Pembrolizumab
Administered via IV infusion at a specified dose on specified days
Vibostolimab
Administered via IV infusion at a specified dose on specified days
Gebasaxturev
Administered via IT injection at a specified dose on specified days
MK-4830
Administered via IV infusion at a specified dose on specified days
Favezelimab + Pembrolizumab
Administered via IV infusion at a specified dose on specified days
ATRA
Administered via oral capsules at a specified dose on specified days
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
* Has been untreated for Stage IIIB, IIIC or IIID melanoma
* surgical resection of primary melanoma is allowed
* prior radiotherapy to the primary melanoma is allowed
* Has provided a baseline tumor biopsy
* Male participants who receive gebasaxturev are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of gebasaxturev
* Male participants who receive 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 ATRA
* Female participants 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, vibostolimab, gebasaxturev, or MK-4830, favezelimab + pembrolizumab, or 30 days after the last dose of 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)
Exclusion Criteria
* 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 monoclonal antibody (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 or live-attenuated 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 only mucosal lesions
* Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses
18 Years
120 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director
Role: STUDY_DIRECTOR
Merck Sharp & Dohme LLC
Locations
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The Angeles Clinic and Research Institute ( Site 3009)
Los Angeles, California, United States
Providence Saint John's Health Center ( Site 3010)
Santa Monica, California, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 3012)
Aurora, Colorado, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 3022)
Baltimore, Maryland, United States
NYU Clinical Cancer Center ( Site 3002)
New York, New York, United States
Duke Cancer Institute ( Site 3005)
Durham, North Carolina, United States
Martha Morehouse Tower ( Site 3020)
Columbus, Ohio, United States
Oregon Health & Science University ( Site 3013)
Portland, Oregon, United States
University of Pennsylvania Abramson Cancer Center ( Site 3008)
Philadelphia, Pennsylvania, United States
West Cancer Center - East Campus ( Site 3014)
Germantown, Tennessee, United States
Inova Schar Cancer Institute ( Site 3011)
Fairfax, Virginia, United States
Melanoma Institute Australia ( Site 3402)
Wollstonecraft, New South Wales, Australia
Tasman Oncology Research Pty Ltd ( Site 3403)
Southport, Queensland, Australia
Fiona Stanley Hospital ( Site 3401)
Murdoch, Western Australia, Australia
Hopital La Timone ( Site 3103)
Marseille, Bouches-du-Rhone, France
Institut Claudius Regaud ( Site 3105)
Toulouse, Haute-Garonne, France
Centre Hospitalier Lyon Sud ( Site 3102)
Pierre-Bénite, Rhone, France
A.P.H. Paris, Hopital Saint Louis ( Site 3107)
Paris, , France
Gustave Roussy ( Site 3101)
Villejuif, Île-de-France Region, France
HaEmek Medical Center ( Site 3703)
Afula, , Israel
Rambam Health Care Campus-Oncology ( Site 3704)
Haifa, , Israel
Hadassah Ein Karem Jerusalem ( Site 3702)
Jerusalem, , Israel
Rabin Medical Center-Oncology ( Site 3705)
Petah Tikva, , Israel
Chaim Sheba Medical Center ( Site 3701)
Ramat Gan, , Israel
Istituto Europeo di Oncologia ( Site 3301)
Milan, , Italy
Policlinico Le Scotte - A.O. Senese ( Site 3377)
Siena, , Italy
Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 3603)
Geneva, Canton of Geneva, Switzerland
CHUV Centre Hospitalier Universitaire Vaudois ( Site 3602)
Lausanne, Canton of Vaud, Switzerland
Universitaetsspital Zuerich ( Site 3601)
Zuerich Flughafen, Canton of Zurich, Switzerland
Countries
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References
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Dummer R, Robert C, Scolyer RA, Taube JM, Tetzlaff MT, Menzies AM, Hill A, Grob JJ, Portnoy DC, Lebbe C, Khattak MA, Cohen J, Bar-Sela G, Mehmi I, Shapira-Frommer R, Meyer N, Webber AL, Ren Y, Fukunaga-Kalabis M, Krepler C, Long GV. Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial. Nat Med. 2025 Jan;31(1):144-151. doi: 10.1038/s41591-024-03411-x. Epub 2025 Jan 7.
Related Links
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Merck Clinical Trials Information
Plain Language Summary
Other Identifiers
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MK-3475-02C
Identifier Type: OTHER
Identifier Source: secondary_id
KEYMAKER-U02
Identifier Type: OTHER
Identifier Source: secondary_id
2023-506314-51-00
Identifier Type: REGISTRY
Identifier Source: secondary_id
U1111-1293-5665
Identifier Type: REGISTRY
Identifier Source: secondary_id
2019-003978-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
3475-02C
Identifier Type: -
Identifier Source: org_study_id
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