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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Sharp & Dohme LLC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

31 Jul 2020 → 24 Sep 2025

Decision date (initial)

2024-02-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506314-51-00

EudraCT number

2019-003978-22

ClinicalTrials.gov

NCT04303169

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacogenomic, Pharmacogenetic, Safety, Dose response, Therapy, Efficacy, Pharmacokinetic

1. To assess the safety and tolerability of investigational treatment combinations based on the proportion of participants with adverse events (AEs).
2. To evaluate pathological complete response (pCR) rate as assessed by central review of the pathology results.

Secondary objectives 3

1. To evaluate the near pathological complete response (near pCR) rate as assessed by central review of the pathology results.
2. To evaluate pathological partial response (pPR) rate as assessed by central review of the pathology results.
3. To evaluate recurrence-free survival (RFS) as assessed by the investigator.

Conditions and MedDRA coding

Stage IIIB or IIIC or IIID melanoma

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Has histologically or cytologically confirmed melanoma
2. Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
3. 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
4. Has provided a baseline tumor biopsy
5. 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
6. 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
7. 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
8. Has adequate organ function
9. Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)

Exclusion criteria 19

1. Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
2. Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
3. Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
4. Has ocular or mucosal melanoma
5. Has known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
6. Has an active autoimmune disease that has required systemic treatment in the past 2 years
7. Has an active infection requiring systemic therapy
8. Has known history of human immunodeficiency virus (HIV)
9. Has known history of hepatitis B
10. Has a history of (noninfectious) pneumonitis
11. Has a history of active tuberculosis (TB)
12. Has received prior systemic anticancer therapy within 4 weeks prior to randomization
13. Has received prior radiotherapy within 2 weeks of first dose of study intervention
14. Has had major surgery <3 weeks prior to first dose of study intervention
15. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
16. Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
17. Has had an allogeneic tissue/solid organ transplant
18. Has only mucosal lesions
19. Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Percentage of participants who experience an adverse event (AE)
2. Percentage of participants who discontinue study treatment due to an AE
3. Pathological complete response (pCR) rate

Secondary endpoints 3

1. Near pathological complete response (near pCR) rate
2. Pathological partial response (pPR) rate
3. Recurrence-free survival (RFS)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Sharp & Dohme LLC

Sponsor organisation

Merck Sharp & Dohme LLC

Address

126 East Lincoln Avenue

City

Rahway

Postcode

07065-4607

Country

United States

Scientific contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Mizuho Kalabis

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Mizuho Kalabis

Third parties 4

Locations

2 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 17 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications