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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04305041




Registration number
NCT04305041
Ethics application status
Date submitted
9/03/2020
Date registered
12/03/2020
Date last updated
20/11/2020

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
2019-003956-35
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 - MK-1308
Other interventions - MK-7684
Treatment: Drugs - Lenvatinib

Experimental: Pembrolizumab + MK-1308 + MK-7684 - Participants will receive pembrolizumab intravenously (IV) plus MK-1308 IV plus MK-7684 IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.

Experimental: Pembrolizumab + MK-1308 + Lenvatinib - Participants will receive pembrolizumab IV plus MK-1308 IV plus lenvatinib 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: MK-1308
Administered via IV infusion at a specified dose on specified days

Other interventions: MK-7684
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

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) - 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.
Timepoint [1] 0 0
Up to ~28 months
Primary outcome [2] 0 0
Percentage of participants who discontinue study treatment due to an AE - 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.
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) - 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 least a 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.
Timepoint [3] 0 0
Up to ~30 months
Secondary outcome [1] 0 0
Duration of Response (DOR) per RECIST 1.1 - For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 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 evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. 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.
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 submitted prestudy imaging

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

- Has provided a tumor biopsy

- Male participants who receive lenvatinib are abstinent from heterosexual intercourse
or agree to use contraception during the intervention period and for at least 5 days
after the last dose of lenvatinib; for male participants who only receive
pembrolizumab, MK-1308, MK-7684, 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, MK-1308, MK-7684 or 30 days
after the last dose of lenvatinib, 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
Gender
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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia ( Site 1402) - Wollstonecraft
Recruitment hospital [2] 0 0
Tasman Oncology Research Pty Ltd ( Site 1403) - Southport
Recruitment hospital [3] 0 0
Fiona Stanley Hospital ( Site 1401) - Murdoch
Recruitment postcode(s) [1] 0 0
2065 - Wollstonecraft
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 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
Oregon
Country [3] 0 0
United States of America
State/province [3] 0 0
Pennsylvania
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
France
State/province [7] 0 0
Bouches-du-Rhone
Country [8] 0 0
France
State/province [8] 0 0
Haute-Garonne
Country [9] 0 0
France
State/province [9] 0 0
Rhone
Country [10] 0 0
France
State/province [10] 0 0
Val-de-Marne
Country [11] 0 0
France
State/province [11] 0 0
Paris
Country [12] 0 0
Israel
State/province [12] 0 0
Tel Aviv
Country [13] 0 0
Israel
State/province [13] 0 0
Yerushalayim
Country [14] 0 0
Italy
State/province [14] 0 0
Toscana
Country [15] 0 0
Switzerland
State/province [15] 0 0
Vaud
Country [16] 0 0
Switzerland
State/province [16] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme Corp.
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.
Trial website
https://clinicaltrials.gov/show/NCT04305041
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme Corp.
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
Trialsites@merck.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04305041