Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants with Melanoma (KEYMAKER-U02): Substudy 02B

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

3 Aug 2020 → 18 May 2026

Decision date (initial)

2024-02-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506313-21-00

EudraCT number

2019-003977-24

WHO UTN

U1111-1293-5644

ClinicalTrials.gov

NCT04305054

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. Safety Lead-in Phase: To assess the safety and tolerability, and to establish an RP2D if applicable, of treatment combinations that have not been evaluated in a separate study.
2. To assess the safety and tolerability of investigational treatment combinations based on the proportion of participants with adverse events (AEs)
3. 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 8

1. Has histologically or cytologically confirmed melanoma
2. Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
3. Has been untreated for advanced disease.
4. Has provided a tumor biopsy
5. If capable of producing sperm, male participants agree to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (7 days): • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR • Uses contraception unless confirmed to be azoospermic
6. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and Uses a contraceptive method that is highly effective, with low user dependency, or be abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is: o MK-4280A: 120 days o MK-1308A: 120 days o MK-7684: 50 days o MK-3475: 120 days o Lenvatinib: 30 days o ATRA: 30 days
7. Has adequate organ function
8. Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia and Grade 2 neuropathy)

Exclusion criteria 18

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 an active autoimmune disease that has required systemic treatment in the past 2 years
6. Has an active infection requiring systemic therapy
7. Has known history of human immunodeficiency virus (HIV)
8. Has history of Hepatitis B or known Hepatitis C virus infection
9. Has a history of (noninfectious) pneumonitis
10. Has a history of active tuberculosis (TB)
11. Has received prior systemic anticancer therapy within 4 weeks prior to randomization
12. Has received prior radiotherapy within 2 weeks of first dose of study intervention
13. Has had major surgery <3 weeks prior to first dose of study intervention
14. Has received a live vaccine within 30 days before the first dose of study intervention
15. Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
16. Has had an allogeneic tissue/solid organ transplant
17. Has a known psychiatric or substance abuse disorder that would interfere with requirements of the study
18. Participants who receive lenvatinib have the following additional exclusion criteria: • Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula • Has radiographic evidence of encasement of invasion of a major blood vessel, or of intratumoral cavitation • Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study intervention • Has clinically significant cardiovascular disease within 12 months from first dose of study intervention • Has urine protein ≥1 g/24-hour. • Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Percentage of participants who experience a dose-limiting toxicity (DLT) during safety lead-in phase
2. Percentage of participants who experience an adverse event (AE) during safety lead-in phase
3. Percentage of participants who discontinue study treatment due to an AE during safety lead-in phase
4. Percentage of participants who experience an adverse event (AE)
5. Percentage of participants who discontinue study treatment due to an AE
6. 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 7

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

Rohit Lal

Public contact point

Organisation

Merck Sharp & Dohme LLC

Contact name

Rohit Lal

Third parties 4

Locations

6 EU/EEA countries · 17 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 65 files

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

Application history

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