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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/NCT04303169
Registration number
NCT04303169
Ethics application status
Date submitted
9/03/2020
Date registered
10/03/2020
Date last updated
26/01/2024
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)
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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
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Secondary ID [1]
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MK-3475-02C
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Secondary ID [2]
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3475-02C
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Melanoma
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Condition category
Condition code
Cancer
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Malignant melanoma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Other interventions - Vibostolimab
Other interventions - Gebasaxturev
Other interventions - MK-4830
Other interventions - 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.
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: Gebasaxturev
Administered via IT injection at a specified dose on specified days
Other interventions: MK-4830
Administered via IV infusion 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 capsules at a specified dose on specified days
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Percentage of participants who experience an adverse event (AE)
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Assessment method [1]
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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.
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Timepoint [1]
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Up to ~16 months
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Primary outcome [2]
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Percentage of participants who discontinue study treatment due to an AE
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Assessment method [2]
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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.
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Timepoint [2]
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Up to ~12 months
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Primary outcome [3]
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Pathological complete response (pCR) rate
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Assessment method [3]
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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.
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Timepoint [3]
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Up to ~1.5 months
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Secondary outcome [1]
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Near pathological complete response (near pCR) rate
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Assessment method [1]
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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.
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Timepoint [1]
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Up to ~1.5 months
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Secondary outcome [2]
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Pathological partial response (pPR) rate
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Assessment method [2]
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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.
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Timepoint [2]
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Up to ~1.5 months
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Secondary outcome [3]
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Recurrence-free survival (RFS)
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Assessment method [3]
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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.
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Timepoint [3]
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Up to ~60 months
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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)
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Minimum age
18
Years
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Maximum age
120
Years
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Sex
Both males and females
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Can healthy volunteers participate?
No
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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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1/Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Active, not recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
26/06/2020
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
3/04/2030
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Actual
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Sample size
Target
90
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
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Recruitment hospital [1]
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Melanoma Institute Australia ( Site 3402) - Wollstonecraft
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Recruitment hospital [2]
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Tasman Oncology Research Pty Ltd ( Site 3403) - Southport
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Recruitment hospital [3]
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Fiona Stanley Hospital ( Site 3401) - Murdoch
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Recruitment postcode(s) [1]
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2065 - Wollstonecraft
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Recruitment postcode(s) [2]
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4215 - Southport
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Recruitment postcode(s) [3]
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6150 - Murdoch
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Recruitment outside Australia
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United States of America
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State/province [1]
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California
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United States of America
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Colorado
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United States of America
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Maryland
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United States of America
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New York
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United States of America
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North Carolina
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Ohio
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United States of America
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Oregon
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Pennsylvania
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United States of America
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Tennessee
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United States of America
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Virginia
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France
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Bouches-du-Rhone
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France
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Haute-Garonne
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France
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Ile-de-France
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France
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Rhone
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France
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Paris
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Israel
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Afula
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Petah-Tikva
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Israel
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Ramat Gan
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Italy
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Milano
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Italy
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Siena
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Switzerland
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Geneve
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Switzerland
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Vaud
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Switzerland
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Zurich
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Merck Sharp & Dohme LLC
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Address
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Ethics approval
Ethics application status
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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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04303169
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Medical Director
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Address
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Merck Sharp & Dohme LLC
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Contact person for public queries
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04303169
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