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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04303169




Registration number
NCT04303169
Ethics application status
Date submitted
9/03/2020
Date registered
10/03/2020
Date last updated
19/11/2024

Titles & IDs
Public title
Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/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 02C
Secondary ID [1] 0 0
MK-3475-02C
Secondary ID [2] 0 0
3475-02C
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 - Vibostolimab
Treatment: Other - Gebasaxturev
Treatment: Other - MK-4830
Treatment: Other - Favezelimab + Pembrolizumab
Treatment: Drugs - ATRA

Experimental: Pembrolizumab + Vibostolimab - Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Experimental: Pembrolizumab + Gebasaxturev - Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus gebasaxturev (V937) intratumorally (IT) at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Experimental: Pembrolizumab - Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Experimental: Pembrolizumab + MK-4830 - Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus MK-4830 IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Experimental: Favezelimab + Pembrolizumab - Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive MK-4280A (favezelimab and pembrolizumab administered as a co-formulation) IV at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.

Experimental: Pembrolizumab + all-trans retinoic acid (ATRA) - Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus ATRA orally at specified doses on specified days. After surgery, in the adjuvant phase, participants will receive pembrolizumab IV at a specified dose on specified days.

Participants will receive treatments in the neoadjuvant and adjuvant phase for a total treatment duration of up to approximately 1 year.


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

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

Treatment: Other: Gebasaxturev
Administered via IT injection at a specified dose on specified days

Treatment: Other: MK-4830
Administered via IV infusion at a specified dose on specified days

Treatment: Other: Favezelimab + Pembrolizumab
Administered via IV infusion 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
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 ~16 months
Primary outcome [2] 0 0
Percentage of participants who discontinue study treatment due to an AE
Timepoint [2] 0 0
Up to ~12 months
Primary outcome [3] 0 0
Pathological complete response (pCR) rate
Timepoint [3] 0 0
Up to ~1.5 months
Secondary outcome [1] 0 0
Near pathological complete response (near pCR) rate
Timepoint [1] 0 0
Up to ~1.5 months
Secondary outcome [2] 0 0
Pathological partial response (pPR) rate
Timepoint [2] 0 0
Up to ~1.5 months
Secondary outcome [3] 0 0
Recurrence-free survival (RFS)
Timepoint [3] 0 0
Up to ~60 months

Eligibility
Key inclusion criteria
* Has histologically or cytologically confirmed melanoma
* Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
* Has been untreated for Stage IIIB, IIIC or IIID melanoma

* surgical resection of primary melanoma is allowed
* prior radiotherapy to the primary melanoma is allowed
* Has provided a baseline tumor biopsy
* Male participants who receive gebasaxturev are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of gebasaxturev
* Male participants who receive 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 ATRA
* 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, vibostolimab, gebasaxturev, or MK-4830, favezelimab + pembrolizumab, or 30 days after the last dose of 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 monoclonal antibody (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 or live-attenuated 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 only mucosal lesions
* Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses

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
26/06/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
3/04/2030
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Melanoma Institute Australia ( Site 3402) - Wollstonecraft
Recruitment hospital [2] 0 0
Tasman Oncology Research Pty Ltd ( Site 3403) - Southport
Recruitment hospital [3] 0 0
Fiona Stanley Hospital ( Site 3401) - 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
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
Virginia
Country [11] 0 0
France
State/province [11] 0 0
Bouches-du-Rhone
Country [12] 0 0
France
State/province [12] 0 0
Haute-Garonne
Country [13] 0 0
France
State/province [13] 0 0
Ile-de-France
Country [14] 0 0
France
State/province [14] 0 0
Rhone
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
Israel
State/province [16] 0 0
Afula
Country [17] 0 0
Israel
State/province [17] 0 0
Haifa
Country [18] 0 0
Israel
State/province [18] 0 0
Jerusalem
Country [19] 0 0
Israel
State/province [19] 0 0
Petah-Tikva
Country [20] 0 0
Israel
State/province [20] 0 0
Ramat Gan
Country [21] 0 0
Italy
State/province [21] 0 0
Milano
Country [22] 0 0
Italy
State/province [22] 0 0
Siena
Country [23] 0 0
Switzerland
State/province [23] 0 0
Geneve
Country [24] 0 0
Switzerland
State/province [24] 0 0
Vaud
Country [25] 0 0
Switzerland
State/province [25] 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 02C 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 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available.

Arm 1: Pembrolizumab + Vibostolimab, Arm 2: Pembrolizumab + Gebasaxturev, and Arm 3: Pembrolizumab were added in the base protocol on 13-Nov-2019, and enrollment into those arms has been completed. Arm 4: Pembrolizumab + MK-4830 was added in Amendment 04 on 20-Dec-2021, and enrollment into that arm has been completed. Arm 5: Favezelimab + Pembrolizumab and Arm 6: Pembrolizumab + all-trans retinoic acid (ATRA) were added in Amendment 06 on 25-Jun-2022, and enrollment is ongoing.
Trial website
https://clinicaltrials.gov/study/NCT04303169
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/NCT04303169