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)
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT04700072
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 300
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Coformulation Pembrolizumab/Quavonlimab + Lenvatinib Pembrolizumab 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. Coformulation Pembrolizumab/Quavonlimab + Lenvatinib Pembrolizumab/Quavonlimab 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. Pembrolizumab + Lenvatinib Pembrolizumab 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. Pembrolizumab + Lenvatinib Lenvatinib 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. Coformulation Pembrolizumab/Quavonlimab + Lenvatinib Lenvatinib 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.
- Primary Outcome Measures
Name Time Method Percentage of participants who experience an adverse event (AE) Up to ~28 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience an AE will be reported.
Percentage of participants who discontinue study treatment due to an AE Up to ~24 months An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinue study treatment due to an AE will be reported.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) Up to ~30 months ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) per RECIST 1.1 Up to ~30 months For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of ≥1 new lesion is also considered PD. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM) Up to ~30 months BMRR is defined as the percentage of participants in the analysis population who achieve a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids and stable or improved clinical status) or PR (≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status). Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases.
Brain metastasis duration of response (BM-DOR) per RANO-BM Up to ~30 months For participants in the analysis population who demonstrate a confirmed intracranial CR (disappearance of all lesions, no usage of corticosteroids, stable or improved clinical status) or PR (≥30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters, no progression of non-target lesions or new lesions, stable or decreased corticosteroid use, or stable or improved clinical status), DOR is defined as the time from first documented CR or PR until PD or death due to any cause, whichever occurs first. Per RANO-BM, PD is defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm in ≥1 lesion. Unequivocal increase in non-target lesions, the appearance of ≥1 new lesion or worsening of clinical status is also considered PD. Responses are according to RANO-BM as assessed by BICR. RANO-BM uses a combination of RECIST 1.1 and clinical data to assess response to treatment in brain metastases.
Progression-free survival (PFS) per RECIST 1.1 Up to ~30 months PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. Responses are according to RECIST 1.1 as assessed by BICR. RECIST 1.1 has been modified for this study to include a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
Trial Locations
- Locations (36)
The Angeles Clinic and Research Institute ( Site 4009)
🇺🇸Los Angeles, California, United States
UCLA Hematology & Oncology ( Site 4004)
🇺🇸Los Angeles, California, United States
Martha Morehouse Tower ( Site 4020)
🇺🇸Columbus, Ohio, United States
Inova Schar Cancer Institute ( Site 4011)
🇺🇸Fairfax, Virginia, United States
Cape Town Oncology Trials ( Site 4864)
🇿🇦Cape Town, Western Cape, South Africa
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 4022)
🇺🇸Baltimore, Maryland, United States
Institut Claudius Regaud ( Site 4105)
🇫🇷Toulouse cedex 9, Haute-Garonne, France
Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 4603)
🇨🇭Genève, Geneve, Switzerland
Istituto Nazionale Tumori Fondazione Pascale ( Site 4302)
🇮🇹Napoli, Italy
Providence Saint John's Health Center ( Site 4010)
🇺🇸Santa Monica, California, United States
NYU Clinical Cancer Center ( Site 4002)
🇺🇸New York, New York, United States
Calvary Mater Newcastle ( Site 4404)
🇦🇺Waratah, New South Wales, Australia
Melanoma Institute Australia ( Site 4402)
🇦🇺Wollstonecraft, New South Wales, Australia
Hopital La Timone ( Site 4103)
🇫🇷Marseille, Bouches-du-Rhone, France
CHU de Bordeaux- Hopital Saint Andre ( Site 4108)
🇫🇷Bordeaux, Gironde, France
Gustave Roussy ( Site 4101)
🇫🇷Villejuif, Ile-de-France, France
A.P.H. Paris, Hopital Saint Louis ( Site 4107)
🇫🇷Paris, France
HaEmek Medical Center ( Site 4703)
🇮🇱Afula, Israel
Centre Hospitalier Lyon Sud ( Site 4102)
🇫🇷Pierre Benite, Rhone, France
Rambam Health Care Campus-Oncology ( Site 4704)
🇮🇱Haifa, Israel
Hadassah Ein Karem Jerusalem ( Site 4702)
🇮🇱Jerusalem, Israel
Rabin Medical Center-Oncology ( Site 4705)
🇮🇱Petah-Tikva, Israel
Chaim Sheba Medical Center ( Site 4701)
🇮🇱Ramat Gan, Israel
Istituto Europeo di Oncologia ( Site 4301)
🇮🇹Milano, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 4399)
🇮🇹Milano, Italy
CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE ( Site 4865)
🇿🇦Port Elizabeth, Eastern Cape, South Africa
Istituto Oncologico Veneto IRCCS ( Site 4355)
🇮🇹Padova, Italy
Policlinico Le Scotte - A.O. Senese ( Site 4377)
🇮🇹Siena, Italy
LIFE GROENKLOOF-Mary Potter Cancer Centre ( Site 4861)
🇿🇦Pretoria, Gauteng, South Africa
Sandton Oncology Medical Group (Pty) Ltd-Research ( Site 4863)
🇿🇦Sandton, Gauteng, South Africa
HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Sit
🇪🇸Barcelona, Cataluna, Spain
Hospital Universitario Ramón y Cajal ( Site 4802)
🇪🇸Madrid, Madrid, Comunidad De, Spain
Universitaetsspital Zuerich ( Site 4601)
🇨🇭Zurich, Switzerland
CHUV Centre Hospitalier Universitaire Vaudois ( Site 4602)
🇨🇭Lausanne, Vaud, Switzerland
University of Colorado, Anschutz Cancer Pavilion ( Site 4012)
🇺🇸Aurora, Colorado, United States
Duke Cancer Institute ( Site 4005)
🇺🇸Durham, North Carolina, United States