Substudy 02D: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Melanoma Brain Metastasis (MK-3475-02D/KEYMAKER-U02)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Melanoma

Treatments: Biological: Pembrolizumab; Drug: Lenvatinib; Biological: Pembrolizumab/Quavonlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04700072

3475-02D

MK-3475-02D (Other Identifier)

KEYMAKER-U02 (Other Identifier)

2020-003742-36 (EudraCT Number)

Details and patient eligibility

About

Substudy 02D 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 02D is to evaluate the safety and efficacy of investigational treatment arms in programmed cell-death 1 (PD-1) naïve or PD-1 exposed participants with melanoma brain metastasis (MBM) and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

As of amendment 2 (effective 01DEC2022) enrollment into the treatment arm of pembrolizumab and lenvatinib has been discontinued.

Enrollment: 300 estimated patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Has American Joint Committee on Cancer (AJCC) Stage IV, M1D melanoma
• Is neurologically asymptomatic from brain metastases and has not received systemic corticosteroid therapy in the 10 days prior to beginning study intervention
• 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
• 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
• 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
• Has adequate organ function
• 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

• Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 10 days before the first dose of study intervention
• Has current or history of known leptomeningeal involvement
• Has received stereotactic or highly conformal radiotherapy within 2 weeks before the start of dosing
• Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
• Has untreated or unresolved intracranial hemorrhage from central nervous system (CNS) metastasis
• Has an active infection requiring systemic therapy
• Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
• Has ocular melanoma
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• Has known history of immunodeficiency virus (HIV)
• Has known history of hepatitis B or known hepatitis C virus
• Has a history of (noninfectious) pneumonitis that required steroids or current pneumonitis
• Has received prior systemic anticancer therapy within 4 weeks prior to randomization/allocation
• Has a history of whole brain irradiation
• 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 prior to the first dose of study intervention
• Has had an allogeneic tissue/solid organ transplant

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 2 patient groups

Coformulation Pembrolizumab/Quavonlimab + Lenvatinib

Experimental group

Description:

Participants will receive pembrolizumab/quavonlimab (coformulation of pembrolizumab and quavonlimab) intravenously (IV) plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Treatment:

Biological: Pembrolizumab/Quavonlimab

Drug: Lenvatinib

Biological: Pembrolizumab

Pembrolizumab + Lenvatinib

Experimental group

Description:

Participants will receive pembrolizumab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Treatment:

Drug: Lenvatinib

Biological: Pembrolizumab