Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/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

25 Jun 2021 → 18 Oct 2025

Decision date (initial)

2024-02-23

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Sharp & Dohme LLC

External identifiers

EU CT number

2023-506315-17-00

EudraCT number

2020-003742-36

WHO UTN

U1111-1293-5704

ClinicalTrials.gov

NCT04700072

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

1. To assess the safety and tolerability of investigational treatment combinations based on the proportion of participations with adverse events (AEs).
2. To evaluate the objective response rate (ORR) as assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1), with modification of measurable lesion criteria ≥0.5 cm in one dimension by magnetic resonance imaging (MRI) and allowing up to 5 intracranial target lesions (in addition to any extracranial target lesions)

Secondary objectives 4

1. To evaluate the duration of response (DOR) as assessed by BICR per RECIST 1.1, with modification of measurable lesion criteria ≥0.5 cm in one dimension by MRI and allowing up to 5 intracranial target lesions (in addition to any extracranial target lesions).
2. To evaluate brain metastasis response rate (BMRR) as assessed by BICR per Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) with modification of measurable lesion criteria ≥0.5 cm in one dimension by MRI and allowing up to 5 intracranial target lesions (in addition to any extracranial target lesions).
3. To evaluate the brain metastasis duration of response (BM-DOR) as assessed by BICR per RANO-BM with modification of measurable lesion criteria ≥0.5 cm in one dimension by MRI and allowing up to 5 intracranial target lesions (in addition to any extracranial target lesions).
4. To evaluate progression-free survival (PFS) as assessed by BICR per RECIST 1.1 with modification of measurable lesion criteria ≥0.5 cm in one dimension by magnetic resonance imaging (MRI) and allowing up to 5 intracranial target lesions (in addition to any extracranial target lesions).

Conditions and MedDRA coding

Advanced melanoma with brain metastases, PD-1 refractory or PD-1 naive

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Has American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma
2. Is neurologically asymptomatic from brain metastases and has not received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
3. 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. The length of time required to continue contraception for each study intervention is: Lenvatinib: 7 days
4. 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
5. Uses contraception unless confirmed to be azoospermic
6. 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 or pembrolizumab/quavonlimab, or 30 days after the last dose of lenvatinib, whichever occurs last
7. Has adequate organ function
8. Female participants agree to abstain from breastfeeding during the study intervention period and for at least the time needed to eliminate study intervention after the last dose of study intervention. The length of time required for each study intervention is: MK-1308A: 120 days MK-3475: 120 days Lenvatinib: 30 days

Exclusion criteria 18

1. Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 10 days before the first dose of study intervention
2. Has current or history of known leptomeningeal involvement
3. Has received stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing
4. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
5. Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS) metastasis
6. Has an active infection requiring systemic therapy
7. Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
8. Has ocular melanoma
9. Has an active autoimmune disease that has required systemic treatment in the past 2 years
10. Has known history of immunodeficiency virus (HIV)
11. Has known history of hepatitis B or known hepatitis C virus
12. Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
13. Has received prior systemic anticancer therapy within 4 weeks prior to randomization/allocation
14. Has a history of whole brain irradiation
15. Has received prior radiotherapy within 2 weeks of first dose of study intervention
16. Has had major surgery <3 weeks prior to first dose of study intervention
17. Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
18. Has had an allogeneic tissue/solid organ transplant

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)

Secondary endpoints 4

1. Duration of Response (DOR)
2. Brain Metastasis Response Rate (BMRR)
3. Brain Metastasis Duration of Response (BM-DOR)
4. Progression-free Survival (PFS)

Investigational products

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

Test 4

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 5

Locations

6 EU/EEA countries · 19 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 40 files

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

Application history

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