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)

Conditions

• Melanoma

Eligibility Criteria

Sex

ALL

Age

18 Years - 120 Years

Healthy Volunteers

Not accepted

Interventions

• Pembrolizumab — BIOLOGICAL
  Administered via IV infusion at a specified dose on specified days
• Vibostolimab — BIOLOGICAL
  Administered via IV infusion at a specified dose on specified days
• Gebasaxturev — BIOLOGICAL
  Administered via IT injection at a specified dose on specified days
• MK-4830 — BIOLOGICAL
  Administered via IV infusion at a specified dose on specified days
• Favezelimab + Pembrolizumab — BIOLOGICAL
  Administered via IV infusion at a specified dose on specified days
• ATRA — DRUG
  Administered via oral capsules at a specified dose on specified days

Study Details

Substudy 02C 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 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.

Key Dates

First listed

Mar 10, 2020

Start date

Jun 26, 2020

Status verified

Aug 2026

Primary completion

Sep 24, 2025

Completion

Sep 24, 2025

Study Design

Enrollment

146 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Pembrolizumab + Vibostolimab
  Neoadjuvant treatment: Participants received pembrolizumab 200 mg by intravenous (IV) infusion administered on Day 1 of a 21-day cycle for 2 cycles, plus vibostolimab 200 mg by IV infusion administered on Day 1 of a 21-day cycle for 2 cycles, prior to surgery. Adjuvant treatment: Following surgery, participants who were disease free with tumor negative margins, as assessed by the investigator, received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 8 cycles. A subset of participants who had confirmed radiographic disease progression with unresectable tumor, unacceptable toxicity, a confirmed positive pregnancy test, withdrawal of consent, or distant metastasis did not receive surgery or adjuvant treatment.
• Experimental: Pembrolizumab + Gebasaxturev
  Neoadjuvant treatment: Participants received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 1 cycle, plus gebasaxturev 3 × 10\^8 tissue culture infectious dose 50%/mL (TCID50) administered intratumorally on Days 1, 3, 5, 8, and 22 of a 42-day cycle for 1 cycle, prior to surgery. Adjuvant treatment: Following surgery, participants who were disease free with tumor negative margins, as assessed by the investigator, received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 8 cycles. A subset of participants who had confirmed radiographic disease progression with unresectable tumor, unacceptable toxicity, a confirmed positive pregnancy test, withdrawal of consent, or distant metastasis did not receive surgery or adjuvant treatment.
• Experimental: Pembrolizumab
  Neoadjuvant treatment: Participants received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 1 cycle, prior to surgery. Adjuvant treatment: Following surgery, participants who were disease free with tumor negative margins, as assessed by the investigator, received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 8 cycles. A subset of participants who had confirmed radiographic disease progression with unresectable tumor, unacceptable toxicity, a confirmed positive pregnancy test, withdrawal of consent, or distant metastasis did not receive surgery or adjuvant treatment.
• Experimental: Pembrolizumab + MK-4830
  Neoadjuvant treatment: Participants received pembrolizumab 200 mg by IV infusion administered on Day 1 of a 21-day cycle for 2 cycles, plus MK-4830 800 mg by IV infusion administered on Day 1 of a 21-day cycle for 2 cycles, prior to surgery. Adjuvant treatment: Following surgery, participants who were disease free with tumor negative margins, as assessed by the investigator, received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 8 cycles. A subset of participants who had confirmed radiographic disease progression with unresectable tumor, unacceptable toxicity, a confirmed positive pregnancy test, withdrawal of consent, or distant metastasis did not receive surgery or adjuvant treatment.
• Experimental: Favezelimab (+) Pembrolizumab
  Neoadjuvant treatment: Participants received a coformulation of favezelimab 800 mg (+) pembrolizumab 200 mg by IV infusion administered on Day 1 of a 21-day cycle for 2 cycles, prior to surgery. Adjuvant treatment: Following surgery, participants who were disease free with tumor negative margins, as assessed by the investigator, received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 8 cycles. A subset of participants who had confirmed radiographic disease progression with unresectable tumor, unacceptable toxicity, a confirmed positive pregnancy test, withdrawal of consent, or distant metastasis did not receive surgery or adjuvant treatment.
• Experimental: Pembrolizumab + All-Trans Retinoic Acid (ATRA)
  Neoadjuvant treatment: Participants received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 1 cycle, plus ATRA 75 mg/m\^2 orally twice a day (bid) on Days 1, 2, and 3 of a 21-day cycle for 2 cycles, prior to surgery. Adjuvant treatment: Following surgery, participants who were disease free with tumor negative margins, as assessed by the investigator, received pembrolizumab 400 mg by IV infusion administered on Day 1 of a 42-day cycle for 8 cycles. A subset of participants who had confirmed radiographic disease progression with unresectable tumor, unacceptable toxicity, a confirmed positive pregnancy test, withdrawal of consent, or distant metastasis did not receive surgery or adjuvant treatment.

Primary Outcome Measure

Percentage of Participants Who Experienced an Adverse Event (AE) [ Time Frame: Up to approximately 17 months ]

Locations (11)

Related coverage on Hipa.ai

• Pembrolizumab melanoma trial posts near pCR rates up to 19.2%
  Pembrolizumab · Aug 27, 2026 · ClinicalTrials.gov

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