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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04303169
Ethics application status
Date submitted
9/03/2020
Date registered
10/03/2020
Date last updated
19/04/2021

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
2019-003978-22
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
Other interventions - Pembrolizumab
Other interventions - Vibostolimab
Other interventions - V937

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 + V937 - Prior to tumor resection surgery, in the neoadjuvant phase, participants will receive pembrolizumab IV plus 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.


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: V937
Administered via IT injection at a specified dose on specified days

Intervention code [1] 0 0
Other interventions
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 ~16 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 ~12 months
Primary outcome [3] 0 0
Pathological complete response (pCR) rate - pCR rate is defined as the proportion of participants with complete absence of viable tumor in the treated tumor bed. Assessments are according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by central review of the pathology results. 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 ~1.5 months
Secondary outcome [1] 0 0
Near pathological complete response (near pCR) rate - Near pCR is defined as the proportion of participants with >0% but =10% of viable tumor cells in the treated tumor bed. Assessments are according to RECIST 1.1 by central review of the pathology results. 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 ~1.5 months
Secondary outcome [2] 0 0
Pathological partial response (pPR) rate - pPR rate is defined as the proportion of participants with >10% but =50% of the treated tumor bed occupied by viable tumor cells. Assessments are according to RECIST 1.1 by central review of the pathology results. 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 [2] 0 0
Up to ~1.5 months
Secondary outcome [3] 0 0
Recurrence-free survival (RFS) - RFS is defined as the time from the date of surgery to (1) any recurrence (local, regional, or distant) as assessed by the investigator or (2) death due to any cause (both cancer and noncancer causes of death). Assessments are according to RECIST 1.1 which 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 ~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 V937 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 V937

- 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, V937, 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 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 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/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)
QLD,WA
Recruitment hospital [1] 0 0
Tasman Oncology Research Pty Ltd ( Site 3403) - Southport
Recruitment hospital [2] 0 0
Fiona Stanley Hospital ( Site 3401) - Murdoch
Recruitment postcode(s) [1] 0 0
4215 - Southport
Recruitment postcode(s) [2] 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
Oregon
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
Tennessee
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
Israel
State/province [14] 0 0
Afula
Country [15] 0 0
Italy
State/province [15] 0 0
Toscana
Country [16] 0 0
Italy
State/province [16] 0 0
Milano
Country [17] 0 0
Switzerland
State/province [17] 0 0
Vaud
Country [18] 0 0
Switzerland
State/province [18] 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 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.
Trial website
https://clinicaltrials.gov/show/NCT04303169
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/NCT04303169