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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04305054




Registration number
NCT04305054
Ethics application status
Date submitted
9/03/2020
Date registered
12/03/2020
Date last updated
22/05/2024

Titles & IDs
Public title
Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/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 02B
Secondary ID [1] 0 0
MK-3475-02B
Secondary ID [2] 0 0
3475-02B
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
Other interventions - Pembrolizumab
Other interventions - Vibostolimab
Other interventions - Pembrolizumab/Quavonlimab
Treatment: Drugs - Lenvatinib
Other interventions - Favezelimab/Pembrolizumab
Treatment: Drugs - ATRA

Experimental: Pembrolizumab + Vibostolimab - Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Active Comparator: Pembrolizumab - Participants will receive pembrolizumab IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.

Experimental: Coformulation Pembrolizumab/Quavonlimab - Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.

Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib - Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Experimental: Coformulation Favezelimab/Pembrolizumab - Participants will receive cofomulation of favezelimab + pembrolizumab (MK-4280A) IV at specified dose on specified days every 3 weeks (Q3W) for up to approximately 2 years

Experimental: Coformulation Favezelimab/Pembrolizumab + All-trans Retinoic Acid (ATRA) - Participants will receive coformulation of favezelimab and pembrolizumab IV Q3W for up to 35 cycles, plus ATRA orally (for 3 days surrounding each infusion of MK-4280A, including Days 1, 2, and 3 of Cycle 1 and on Days -1, 1, and 2 of all subsequent cycles).

Experimental: Coformulation Favezelimab/Pembrolizumab + Vibostolimab - Participants will receive coformulation of favezelimab and pembrolizumab (MK-4280A) IV and vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.


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

Other interventions: Vibostolimab
Administered via IV infusion at a specified dose on specified days

Other interventions: 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

Other interventions: Favezelimab/Pembrolizumab
Administered via IV infusion at a specified dose on specified days

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

Outcomes
Primary outcome [1] 0 0
Percentage of participants who experience a dose-limiting toxicity (DLT): Safety lead-in phase
Timepoint [1] 0 0
Up to ~3 weeks
Primary outcome [2] 0 0
Percentage of participants who experience an adverse event (AE): Safety lead-in
Timepoint [2] 0 0
Up to ~3 weeks
Primary outcome [3] 0 0
Percentage of participants who discontinue study treatment due to an AE: Safety lead-in
Timepoint [3] 0 0
Up to ~3 weeks
Primary outcome [4] 0 0
Percentage of participants who experience an adverse event (AE)
Timepoint [4] 0 0
Up to ~28 months
Primary outcome [5] 0 0
Percentage of participants who discontinue study treatment due to an AE
Timepoint [5] 0 0
Up to ~24 months
Primary outcome [6] 0 0
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Timepoint [6] 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

Eligibility
Key inclusion criteria
- Has histologically or cytologically confirmed melanoma

- Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy

- Has been untreated for advanced disease.

- Has provided a tumor biopsy

- 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 (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

- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:

- Is not a WOCBP OR

- Is a WOCBP and Uses a contraceptive method that is highly effective, with low
user dependency, or be abstinent from penile-vaginal intercourse as their
preferred and usual lifestyle (abstinent on a long-term and persistent basis)
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:

- MK-4280A: 120 days

- MK-1308A: 120 days

- MK-7684: 50 days

- MK-3475: 120 days

- Lenvatinib: 30 days

- ATRA: 30 days

- Has adequate organ function

- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less
(except alopecia and Grade 2 neuropathy)
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 7
days before the first dose of study intervention

- Has a known additional malignancy that is progressing or requires active treatment
within the past 2 years

- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis

- Has ocular or mucosal melanoma

- Has an active autoimmune disease that has required systemic treatment in the past 2
years

- Has an active infection requiring systemic therapy

- Has known history of human immunodeficiency virus (HIV)

- Has history of Hepatitis B or known Hepatitis C virus infection

- Has a history of (noninfectious) pneumonitis

- Has a history of active tuberculosis (TB)

- Has received prior systemic anticancer therapy within 4 weeks prior to randomization

- 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 vaccine within 30 days before the first dose of study intervention

- Has participated in a study of an investigational agent within 4 weeks prior to the
first dose of study intervention

- Has had an allogeneic tissue/solid organ transplant

- Has a known psychiatric or substance abuse disorder that would interfere with
requirements of the study

- Participants who receive lenvatinib have the following additional exclusion criteria:

- Has a pre-existing Grade =3 gastrointestinal or non-gastrointestinal fistula

- Has radiographic evidence of encasement of invasion of a major blood vessel, or
of intratumoral cavitation

- Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to
the first dose of study intervention

- Has clinically significant cardiovascular disease within 12 months from first
dose of study intervention

- Has urine protein =1 g/24-hour.

- Has presence of gastrointestinal condition including malabsorption,
gastrointestinal anastomosis, or any other condition that might affect the
absorption of lenvatinib

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/Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/04/2030
Actual
Sample size
Target
315
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle-Medical Oncology ( Site 2404) - Waratah
Recruitment hospital [2] 0 0
Melanoma Institute Australia ( Site 2402) - Wollstonecraft
Recruitment hospital [3] 0 0
Tasman Oncology Research Pty Ltd ( Site 2403) - Southport
Recruitment hospital [4] 0 0
Fiona Stanley Hospital ( Site 2401) - Murdoch
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [3] 0 0
4120 - Southport
Recruitment postcode(s) [4] 0 0
6150 - Murdoch
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
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
North Carolina
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Virginia
Country [13] 0 0
Argentina
State/province [13] 0 0
Buenos Aires
Country [14] 0 0
Chile
State/province [14] 0 0
Araucania
Country [15] 0 0
Chile
State/province [15] 0 0
Coquimbo
Country [16] 0 0
Chile
State/province [16] 0 0
Region M. De Santiago
Country [17] 0 0
Colombia
State/province [17] 0 0
Distrito Capital De Bogota
Country [18] 0 0
Colombia
State/province [18] 0 0
Valle Del Cauca
Country [19] 0 0
France
State/province [19] 0 0
Bouches-du-Rhone
Country [20] 0 0
France
State/province [20] 0 0
Gironde
Country [21] 0 0
France
State/province [21] 0 0
Haute-Garonne
Country [22] 0 0
France
State/province [22] 0 0
Ile-de-France
Country [23] 0 0
France
State/province [23] 0 0
Rhone
Country [24] 0 0
France
State/province [24] 0 0
Paris
Country [25] 0 0
Greece
State/province [25] 0 0
Attiki
Country [26] 0 0
Greece
State/province [26] 0 0
Thessaloniki
Country [27] 0 0
Hungary
State/province [27] 0 0
Csongrad
Country [28] 0 0
Israel
State/province [28] 0 0
Afula
Country [29] 0 0
Israel
State/province [29] 0 0
Haifa
Country [30] 0 0
Israel
State/province [30] 0 0
Jerusalem
Country [31] 0 0
Israel
State/province [31] 0 0
Petah-Tikva
Country [32] 0 0
Israel
State/province [32] 0 0
Ramat Gan
Country [33] 0 0
Italy
State/province [33] 0 0
Milano
Country [34] 0 0
Italy
State/province [34] 0 0
Napoli
Country [35] 0 0
Italy
State/province [35] 0 0
Padova
Country [36] 0 0
Italy
State/province [36] 0 0
Siena
Country [37] 0 0
Poland
State/province [37] 0 0
Mazowieckie
Country [38] 0 0
Poland
State/province [38] 0 0
Pomorskie
Country [39] 0 0
South Africa
State/province [39] 0 0
Eastern Cape
Country [40] 0 0
South Africa
State/province [40] 0 0
Gauteng
Country [41] 0 0
South Africa
State/province [41] 0 0
Western Cape
Country [42] 0 0
Spain
State/province [42] 0 0
Cataluna
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid, Comunidad De
Country [44] 0 0
Switzerland
State/province [44] 0 0
Geneve
Country [45] 0 0
Switzerland
State/province [45] 0 0
Vaud
Country [46] 0 0
Switzerland
State/province [46] 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 02B 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 02B is to evaluate the safety and efficacy of investigational treatment
arms in participants with 1L advanced melanoma and to identify the investigational agent(s)
that, when used in combination, are superior to the current treatment options/pembrolizumab
monotherapy.

Arm 1: Pembrolizumab + Vibostolimab was added in the base protocol on 13-Nov-2019, and
enrollment into this arm has been completed. Arm 2: Pembrolizumab was added in the base
protocol on 13-Nov-2019, and enrollment stopped prematurely on 15-Aug-2022. Arm 3:
Coformulation Pembrolizumab/Quavonlimab was added in Amendment 01 on 20-Oct-2020, and
enrollment stopped prematurely on 15-Aug-2022. Arm 4: Coformulation Pembrolizumab/Quavonlimab
+ Lenvatinib was added in Amendment 01 on 20-Oct-2020, and enrollment is ongoing. Arm 5:
Coformulation Favezelimab/Pembrolizumab, Arm 6: Coformulation Favezelimab/Pembrolizumab +
All-trans Retinoic Acid (ATRA), and Arm 7: Coformulation Favezelimab/Pembrolizumab +
Vibostolimab were added in Amendment 04 on 10-May-2023, and enrollment for these arms will be
initiated in July 2023.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04305054
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
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04305054