Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/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

30 Jul 2020 → 25 Aug 2025

Decision date (initial)

2023-12-04

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC.

External identifiers

EU CT number

2023-506312-41-00

EudraCT number

2019-003956-35

WHO UTN

U1111-1293-5630

ClinicalTrials.gov

NCT04305041

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To assess the safety and tolerability of investigational treatment combinations based on the proportion of participants with adverse events (AEs)
2. To evaluate objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Secondary objectives 1

1. To evaluate the duration of response (DOR) as assessed by BICR per RECIST 1.1

Conditions and MedDRA coding

PD-1 refractory melanoma

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Has histologically or cytologically confirmed melanoma.
2. Has unresectable Stage III or Stage IV melanoma, per AJCC 8th Edition Staging Criteria, not amenable to local therapy.
3. Has progressed on treatment with an anti-PD-1/L1 mAb administered either as monotherapy, or in combination with other therapies.
4. Has imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in the setting of rapid progression.
5. Has not received more than 3 lines of therapy for their advanced melanoma.
6. Has provided a tumor biopsy.
7. Male participants who receive lenvatinib or 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 lenvatinib or ATRA; for male participants who only receive pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception measures are needed.
8. Female participant 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, quavonlimab, vibostolimab or 30 days after the last dose of lenvatinib or ATRA, whichever occurs last.
9. Has adequate organ function.
10. Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia).

Exclusion criteria 21

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 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 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 a pre-existing Grade ≥3 gastrointestinal fistula or non-gastrointestinal fistula.
19. Has radiographic evidence of encasement of invasion of major blood vessel or of intratumoral cavitation.
20. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention.
21. Has clinically significant cardiovascular disease within 12 months from first dose of study intervention.

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. Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Secondary endpoints 1

1. Duration of response (DOR) per RECIST 1.1

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

Rohini Singh

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Rohini Singh

Third parties 5

Locations

2 EU/EEA countries · 11 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 10 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