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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04700072




Registration number
NCT04700072
Ethics application status
Date submitted
5/01/2021
Date registered
7/01/2021
Date last updated
19/11/2024

Titles & IDs
Public title
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)
Scientific 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
Secondary ID [1] 0 0
MK-3475-02D
Secondary ID [2] 0 0
3475-02D
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Pembrolizumab
Treatment: Other - Pembrolizumab/Quavonlimab
Treatment: Drugs - Lenvatinib

Experimental: Coformulation Pembrolizumab/Quavonlimab + 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.

Experimental: Pembrolizumab + 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.


Treatment: Other: Pembrolizumab
Administered via IV infusion at a specified dose on specified days

Treatment: Other: Pembrolizumab/Quavonlimab
Administered via IV infusion at a specified dose on specified days

Treatment: Drugs: Lenvatinib
Administered via oral capsule at a specified dose on specified days
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of participants who experience an adverse event (AE)
Timepoint [1] 0 0
Up to ~28 months
Primary outcome [2] 0 0
Percentage of participants who discontinue study treatment due to an AE
Timepoint [2] 0 0
Up to ~24 months
Primary outcome [3] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Timepoint [3] 0 0
Up to ~30 months
Secondary outcome [1] 0 0
Duration of Response (DOR) per RECIST 1.1
Timepoint [1] 0 0
Up to ~30 months
Secondary outcome [2] 0 0
Brain metastasis response rate (BMRR) per Response Assessment in Neuro- Oncology Brain Metastases (RANO-BM)
Timepoint [2] 0 0
Up to ~30 months
Secondary outcome [3] 0 0
Brain metastasis duration of response (BM-DOR) per RANO-BM
Timepoint [3] 0 0
Up to ~30 months
Secondary outcome [4] 0 0
Progression-free survival (PFS) per RECIST 1.1
Timepoint [4] 0 0
Up to ~30 months

Eligibility
Key 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
Minimum age
18 Years
Maximum age
120 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/05/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/04/2030
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Calvary Mater Newcastle ( Site 4404) - Waratah
Recruitment hospital [2] 0 0
Melanoma Institute Australia ( Site 4402) - Wollstonecraft
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
2065 - Wollstonecraft
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Virginia
Country [8] 0 0
France
State/province [8] 0 0
Bouches-du-Rhone
Country [9] 0 0
France
State/province [9] 0 0
Gironde
Country [10] 0 0
France
State/province [10] 0 0
Haute-Garonne
Country [11] 0 0
France
State/province [11] 0 0
Ile-de-France
Country [12] 0 0
France
State/province [12] 0 0
Rhone
Country [13] 0 0
France
State/province [13] 0 0
Paris
Country [14] 0 0
Israel
State/province [14] 0 0
Afula
Country [15] 0 0
Israel
State/province [15] 0 0
Haifa
Country [16] 0 0
Israel
State/province [16] 0 0
Jerusalem
Country [17] 0 0
Israel
State/province [17] 0 0
Petah-Tikva
Country [18] 0 0
Israel
State/province [18] 0 0
Ramat Gan
Country [19] 0 0
Italy
State/province [19] 0 0
Milano
Country [20] 0 0
Italy
State/province [20] 0 0
Napoli
Country [21] 0 0
Italy
State/province [21] 0 0
Padova
Country [22] 0 0
Italy
State/province [22] 0 0
Siena
Country [23] 0 0
South Africa
State/province [23] 0 0
Eastern Cape
Country [24] 0 0
South Africa
State/province [24] 0 0
Gauteng
Country [25] 0 0
South Africa
State/province [25] 0 0
Western Cape
Country [26] 0 0
Spain
State/province [26] 0 0
Cataluna
Country [27] 0 0
Spain
State/province [27] 0 0
Madrid, Comunidad De
Country [28] 0 0
Switzerland
State/province [28] 0 0
Geneve
Country [29] 0 0
Switzerland
State/province [29] 0 0
Vaud
Country [30] 0 0
Switzerland
State/province [30] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT04700072
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04700072