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MelanomaPhase 1/2NCT04303169

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)

A Phase 1/2 study testing Pembrolizumab, Vibostolimab and Gebasaxturev in people with Melanoma, run by Merck Sharp & Dohme LLC at 29 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 to 120 years
Conditions the study is for
Melanoma
What is being tested?
Pembrolizumab, Vibostolimab and Gebasaxturev
Could I receive a placebo?
No, everyone receives an active treatment
How many people
146 participants
Where
29 sitesin 6 countries
Study dates
26 Jun 2020to 24 Sep 2025
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Has histologically or cytologically confirmed melanoma
  • 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 and re-resection of primary melanoma is allowed
  • Prior radiotherapy to the primary melanoma is allowed
  • Has provided a baseline tumor biopsy
Show all 11Show fewer
  • 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 all-trans retinoic acid (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)

Who cannot join

  • 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 monoclonal antibody (mAb)
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years
Show all 19Show fewer
  • 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

Trial locations and contacts

29 sites in 6 countries.

29 sites in 6 countries

United States11 sites

  • University of Colorado, Anschutz Cancer Pavilion ( Site 3012)

    Aurora, Colorado, 80045

  • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 3022)

    Baltimore, Maryland, 21287

  • Martha Morehouse Tower ( Site 3020)

    Columbus, Ohio, 43221

  • Duke Cancer Institute ( Site 3005)

    Durham, North Carolina, 27710

  • Inova Schar Cancer Institute ( Site 3011)

    Fairfax, Virginia, 22031

  • West Cancer Center - East Campus ( Site 3014)

    Germantown, Tennessee, 38138

  • The Angeles Clinic and Research Institute ( Site 3009)

    Los Angeles, California, 90025

  • NYU Clinical Cancer Center ( Site 3002)

    New York, New York, 10016

  • University of Pennsylvania Abramson Cancer Center ( Site 3008)

    Philadelphia, Pennsylvania, 19104

  • Oregon Health & Science University ( Site 3013)

    Portland, Oregon, 97239

  • Providence Saint John's Health Center ( Site 3010)

    Santa Monica, California, 90404

Other trials in United States

France5 sites

  • Hopital La Timone ( Site 3103)

    Marseille, Bouches-du-Rhone, 13005

  • A.P.H. Paris, Hopital Saint Louis ( Site 3107)

    Paris, 75010

  • Centre Hospitalier Lyon Sud ( Site 3102)

    Pierre-Bénite, Rhone, 69495

  • Institut Claudius Regaud ( Site 3105)

    Toulouse, Haute-Garonne, 31059

  • Gustave Roussy ( Site 3101)

    Villejuif, Île-de-France Region, 94805

Other trials in France

Israel5 sites

  • HaEmek Medical Center ( Site 3703)

    Afula, 1834111

  • Rambam Health Care Campus-Oncology ( Site 3704)

    Haifa, 3109601

  • Hadassah Ein Karem Jerusalem ( Site 3702)

    Jerusalem, 9112001

  • Rabin Medical Center-Oncology ( Site 3705)

    Petah Tikva, 4941492

  • Chaim Sheba Medical Center ( Site 3701)

    Ramat Gan, 5265601

Other trials in Israel

Australia3 sites

  • Fiona Stanley Hospital ( Site 3401)

    Murdoch, Western Australia, 6150

  • Tasman Oncology Research Pty Ltd ( Site 3403)

    Southport, Queensland, 4215

  • Melanoma Institute Australia ( Site 3402)

    Wollstonecraft, New South Wales, 2065

Other trials in Australia

Switzerland3 sites

  • Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 3603)

    Geneva, Canton of Geneva, 1211

  • CHUV Centre Hospitalier Universitaire Vaudois ( Site 3602)

    Lausanne, Canton of Vaud, 1011

  • Universitaetsspital Zuerich ( Site 3601)

    Zuerich Flughafen, Canton of Zurich, 8058

Other trials in Switzerland

Italy2 sites

  • Istituto Europeo di Oncologia ( Site 3301)

    Milan, 20141

  • Policlinico Le Scotte - A.O. Senese ( Site 3377)

    Siena, 53100

Other trials in Italy

About this study

Official title: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02C

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.

Conditions
Melanoma
Being tested
Pembrolizumab, Vibostolimab, Gebasaxturev, MK-4830, Favezelimab + Pembrolizumab
Keywords
programmed cell death 1 (PD-1, PD1), programmed cell death ligand 1 (PD-L1, PDL1), Coxsackievirus A21, Intracellular Adhesion Molecule-1 (ICAM-1), T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domains (TIGIT)
Medical subject headings
Melanoma, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabBiological

    Also called MK-3475, KEYTRUDA®

    Administered via IV infusion at a specified dose on specified days

  • VibostolimabBiological

    Also called MK-7684

    Administered via IV infusion at a specified dose on specified days

  • GebasaxturevBiological

    Also called Coxsackievirus A21 (CVA21), Formerly known as CAVATAK®, CAV21, V937

    Administered via IT injection at a specified dose on specified days

  • MK-4830Biological

    Administered via IV infusion at a specified dose on specified days

  • Favezelimab + PembrolizumabBiological

    Also called MK-4280A

    Administered via IV infusion at a specified dose on specified days

  • ATRADrug

    Also called Tretinoin, Vesanoid®

    Administered via oral capsules at a specified dose on specified days

Study groups in NCT04303169
Study groupRoleWhat they receive
Pembrolizumab + VibostolimabExperimentalNeoadjuvant 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.
Receives: Biological: Pembrolizumab; Biological: Vibostolimab
Pembrolizumab + GebasaxturevExperimentalNeoadjuvant 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.
Receives: Biological: Pembrolizumab; Biological: Gebasaxturev
PembrolizumabExperimentalNeoadjuvant 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.
Receives: Biological: Pembrolizumab
Pembrolizumab + MK-4830ExperimentalNeoadjuvant 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.
Receives: Biological: Pembrolizumab; Biological: MK-4830
Favezelimab (+) PembrolizumabExperimentalNeoadjuvant 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.
Receives: Biological: Favezelimab + Pembrolizumab
Pembrolizumab + All-Trans Retinoic Acid (ATRA)ExperimentalNeoadjuvant 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.
Receives: Biological: Pembrolizumab; Drug: ATRA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Who Experienced an Adverse Event (AE)

    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 experienced an AE was reported.

    Measured: Up to approximately 17 months

  2. Percentage of Participants Who Discontinued Study Intervention Due to an AE

    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 discontinued study intervention due to an AE was reported.

    Measured: Up to approximately 13 months

  3. Pathological Complete Response (pCR) Rate With 90% Confidence Interval (CI)

    pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 90% CI was reported.

    Measured: Up to approximately 6 weeks

  4. pCR Rate With 95% CI

    pCR rate was defined as the percentage of participants with complete absence of viable tumor in the treated tumor bed as assessed by central review of the pathology results. Per protocol, pCR rate with 95% CI was reported.

    Measured: Up to approximately 6 weeks

Secondary outcomes (5)

  1. Near pCR Rate With 90% CI

    Near pCR was defined as the percentage of participants with >0% but ≤10% of viable tumor cells in the treated tumor bed as assessed by central review of the pathology results. Per protocol, near pCR rate with 90% CI was reported.

    Measured: Up to approximately 6 weeks

  2. Near pCR Rate With 95% CI

    Near pCR was defined as the percentage of participants with >0% but ≤10% of viable tumor cells in the treated tumor bed as assessed by central review of the pathology results. Per protocol, near pCR rate with 95% CI was reported.

    Measured: Up to approximately 6 weeks

  3. Pathological Partial Response (pPR) Rate With 90% CI

    pPR rate was defined as the percentage of participants with >10% but ≤50% of the treated tumor bed occupied by viable tumor cells as assessed by central review of the pathology results. Per protocol, pPR rate with 90% CI was reported.

    Measured: Up to approximately 6 weeks

  4. pPR Rate With 95% CI

    pPR rate was defined as the percentage of participants with >10% but ≤50% of the treated tumor bed occupied by viable tumor cells as assessed by central review of the pathology results. Per protocol, pPR rate with 95% CI was reported.

    Measured: Up to approximately 6 weeks

  5. Recurrence-Free Survival (RFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by The Investigator

    RFS was defined as the time from the date of surgery to (1) any recurrence (local, regional, or distant) per RECIST 1.1 as assessed by the investigator or (2) death due to any cause (both cancer and noncancer causes of death). Per protocol, RECIST 1.1 was modified to allow up to 10 target lesions total (up to 5 per organ). Per protocol, RFS per RECIST 1.1 as assessed by the investigator was presented.

    Measured: Up to approximately 62 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2020
  2. Study start26 Jun 2020
  3. Primary completion24 Sep 2025
  4. Study completion24 Sep 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
146 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04303169
Sponsor's protocol ID
3475-02C
Other IDs
MK-3475-02C, KEYMAKER-U02, 2023-506314-51-00, U1111-1293-5665, 2019-003978-22, 2019, 2023
Status last verified
Aug 2026
First submitted
9 Mar 2020
Last updated
27 Aug 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Publications

  • 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.

    PubMed 39775043

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab, Vibostolimab and Gebasaxturev in people with Melanoma, run by Merck Sharp & Dohme LLC at 29 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, France, Israel, Australia, Switzerland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Experienced an Adverse Event (AE) (time frame: Up to approximately 17 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04303169, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2026.

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