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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/NCT04305041




Registration number
NCT04305041
Ethics application status
Date submitted
9/03/2020
Date registered
12/03/2020
Date last updated
27/12/2023

Titles & IDs
Public title
Substudy 02A: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents in Participants With Programmed Cell-death 1 (PD-1) Refractory Melanoma (MK-3475-02A/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 02A
Secondary ID [1] 0 0
MK-3475-02A
Secondary ID [2] 0 0
3475-02A
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 - Quavonlimab
Other interventions - Vibostolimab
Treatment: Drugs - Lenvatinib
Treatment: Drugs - ATRA

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

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

Experimental: Pembrolizumab + all-trans retinoic acid (ATRA) - Participants will receive pembrolizumab IV plus ATRA orally 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: Quavonlimab
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

Treatment: Drugs: Lenvatinib
Administered via oral capsules at a specified dose on specified days

Treatment: Drugs: ATRA
Administered via oral capsules 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 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

Eligibility
Key inclusion criteria
- Has histologically or cytologically confirmed melanoma

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

- Has progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb)
administered either as monotherapy, or in combination with other therapies

- Has imaging documenting progression per RECIST 1.1 and iRECIST after initiation of an
anti-PD-1/L1 agent, or by RECIST 1.1 if progression occurred on adjuvant therapy or in
the setting of rapid progression.

- Has not received more than 3 lines of therapy for their advanced melanoma

- Has provided a tumor biopsy

- Male participants who receive lenvatinib or ATRA are abstinent from heterosexual
intercourse or agree to use contraception during the intervention period and for at
least 7 days after the last dose of lenvatinib or ATRA; for male participants who only
receive pembrolizumab, quavonlimab, vibostolimab, or a combination, no contraception
measures are needed

- Female participant 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, quavonlimab, vibostolimab or
30 days after the last dose of lenvatinib or ATRA, whichever occurs last

- Has adequate organ function

- Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less
(except alopecia)
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 known hypersensitivity including previous clinically significant hypersensitivity
reaction to treatment with another mAb

- 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 known history of hepatitis B

- 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 pre-existing Grade =3 gastrointestinal fistula or nongastrointestinal fistula

- Has radiographic evidence of encasement of invasion of 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

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
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/04/2030
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Calvary Mater Newcastle-Medical Oncology ( Site 1404) - Waratah
Recruitment hospital [2] 0 0
Melanoma Institute Australia ( Site 1402) - Wollstonecraft
Recruitment hospital [3] 0 0
Tasman Oncology Research Pty Ltd ( Site 1403) - Southport
Recruitment hospital [4] 0 0
Fiona Stanley Hospital ( Site 1401) - Murdoch
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [3] 0 0
4215 - 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
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
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
France
State/province [12] 0 0
Bouches-du-Rhone
Country [13] 0 0
France
State/province [13] 0 0
Gironde
Country [14] 0 0
France
State/province [14] 0 0
Haute-Garonne
Country [15] 0 0
France
State/province [15] 0 0
Ile-de-France
Country [16] 0 0
France
State/province [16] 0 0
Rhone
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
Israel
State/province [18] 0 0
Afula
Country [19] 0 0
Israel
State/province [19] 0 0
Haifa
Country [20] 0 0
Israel
State/province [20] 0 0
Jerusalem
Country [21] 0 0
Israel
State/province [21] 0 0
Ramat Gan
Country [22] 0 0
Italy
State/province [22] 0 0
Milano
Country [23] 0 0
Italy
State/province [23] 0 0
Napoli
Country [24] 0 0
Italy
State/province [24] 0 0
Padova
Country [25] 0 0
Italy
State/province [25] 0 0
Siena
Country [26] 0 0
Switzerland
State/province [26] 0 0
Geneve
Country [27] 0 0
Switzerland
State/province [27] 0 0
Vaud
Country [28] 0 0
Switzerland
State/province [28] 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 02A 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 02A is to evaluate the safety and efficacy of investigational treatment
arms in participants with PD-1 refractory melanoma to identify the investigational agent(s)
that, when used in combination, are superior to the current treatment options/historical
control available.

As of Amendment 4 (effective date: 05JAN2022), a third arm has been opened to participant
enrollment, treatment with pembrolizumab and all-trans retinoic acid (ATRA). Enrollment into
the first two arms, treatment with pembrolizumab + quavonlimab+ vibostolimab and treatment
with pembrolizumab + quavonlimab + lenvatinib has been completed per protocol as of September
2021.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04305041
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