Clinical trial NCT04700072: 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)
Official title: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants With Melanoma (KEYMAKER-U02): Substudy 02D
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Melanoma
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2021-01-07
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of participants who experience an adverse event (AE)
timeFrame: Up to ~28 months
measure: Percentage of participants who discontinue study treatment due to an AE
timeFrame: Up to ~24 months
measure: Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
timeFrame: Up to ~30 months
Secondary outcomes:
measure: Duration of Response (DOR) per RECIST 1.1
timeFrame: Up to ~30 months
measure: Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM)
timeFrame: Up to ~30 months
measure: Brain metastasis duration of response (BM-DOR) per RANO-BM
timeFrame: Up to ~30 months
measure: Progression-free survival (PFS) per RECIST 1.1
timeFrame: Up to ~30 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute ( Site 4009)
state: California
city: Los Angeles
country: United States
facility: UCLA Hematology & Oncology ( Site 4004)
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center ( Site 4010)
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Cancer Pavilion ( Site 4012)
state: Colorado
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 4022)
state: Maryland
city: New York
country: United States
facility: NYU Clinical Cancer Center ( Site 4002)
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute ( Site 4005)
state: North Carolina
city: Columbus
country: United States
facility: Martha Morehouse Tower ( Site 4020)
state: Ohio
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute ( Site 4011)
state: Virginia
city: Waratah
country: Australia
facility: Calvary Mater Newcastle ( Site 4404)
state: New South Wales
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia ( Site 4402)
state: New South Wales
city: Marseille
country: France
facility: Hopital La Timone ( Site 4103)
state: Bouches-du-Rhone
city: Bordeaux
country: France
facility: CHU de Bordeaux- Hopital Saint Andre ( Site 4108)
state: Gironde
city: Toulouse cedex 9
country: France
facility: Institut Claudius Regaud ( Site 4105)
state: Haute-Garonne
city: Villejuif
country: France
facility: Gustave Roussy ( Site 4101)
state: Ile-de-France
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud ( Site 4102)
state: Rhone
city: Paris
country: France
facility: A.P.H. Paris, Hopital Saint Louis ( Site 4107)
city: Afula
country: Israel
facility: HaEmek Medical Center ( Site 4703)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 4704)
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Jerusalem ( Site 4702)
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center-Oncology ( Site 4705)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 4701)
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 4399)
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia ( Site 4301)
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Pascale ( Site 4302)
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS ( Site 4355)
city: Siena
country: Italy
facility: Policlinico Le Scotte - A.O. Senese ( Site 4377)
city: Port Elizabeth
country: South Africa
facility: CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 4865)
state: Eastern Cape
city: Pretoria
country: South Africa
facility: LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 4861)
state: Gauteng
city: Sandton
country: South Africa
facility: Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 4863)
state: Gauteng
city: Cape Town
country: South Africa
facility: Cape Town Oncology Trials ( Site 4864)
state: Western Cape
city: Barcelona
country: Spain
facility: HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Site 4801)
state: Cataluna
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal ( Site 4802)
state: Madrid, Comunidad De
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 4603)
state: Geneve
city: Lausanne
country: Switzerland
facility: CHUV Centre Hospitalier Universitaire Vaudois ( Site 4602)
state: Vaud
city: Zurich
country: Switzerland
facility: Universitaetsspital Zuerich ( Site 4601)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: