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)
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT04303169
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 90
-
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
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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
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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)
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab + Vibostolimab Pembrolizumab 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. Pembrolizumab + Gebasaxturev Pembrolizumab 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. Pembrolizumab + Vibostolimab 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. Favezelimab + Pembrolizumab 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. Pembrolizumab + all-trans retinoic acid (ATRA) 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. Pembrolizumab + Gebasaxturev 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. Pembrolizumab + all-trans retinoic acid (ATRA) Pembrolizumab 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. Pembrolizumab 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. Pembrolizumab + MK-4830 Pembrolizumab 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. Pembrolizumab + MK-4830 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.
- Primary Outcome Measures
Name Time Method Pathological complete response (pCR) rate Up to ~1.5 months 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.
Percentage of participants who experience an adverse event (AE) Up to ~16 months 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.
Percentage of participants who discontinue study treatment due to an AE Up to ~12 months 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.
- Secondary Outcome Measures
Name Time Method Near pathological complete response (near pCR) rate Up to ~1.5 months 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.
Pathological partial response (pPR) rate Up to ~1.5 months 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.
Recurrence-free survival (RFS) Up to ~60 months 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.
Trial Locations
- Locations (29)
Istituto Europeo di Oncologia ( Site 3301)
🇮🇹Milano, Italy
Policlinico Le Scotte - A.O. Senese ( Site 3377)
🇮🇹Siena, Italy
The Angeles Clinic and Research Institute ( Site 3009)
🇺🇸Los Angeles, California, United States
Inova Schar Cancer Institute ( Site 3011)
🇺🇸Fairfax, Virginia, United States
Martha Morehouse Tower ( Site 3020)
🇺🇸Columbus, Ohio, United States
West Cancer Center - East Campus ( Site 3014)
🇺🇸Germantown, Tennessee, United States
University of Pennsylvania Abramson Cancer Center ( Site 3008)
🇺🇸Philadelphia, Pennsylvania, United States
CHUV Centre Hospitalier Universitaire Vaudois ( Site 3602)
🇨🇭Lausanne, Vaud, Switzerland
Hopital La Timone ( Site 3103)
🇫🇷Marseille, Bouches-du-Rhone, France
Fiona Stanley Hospital ( Site 3401)
🇦🇺Murdoch, Western Australia, Australia
Gustave Roussy ( Site 3101)
🇫🇷Villejuif, Ile-de-France, France
Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 3603)
🇨🇭Genève, Geneve, Switzerland
Hadassah Ein Karem Jerusalem ( Site 3702)
🇮🇱Jerusalem, Israel
Universitaetsspital Zuerich ( Site 3601)
🇨🇭Zuerich Flughafen, Zurich, Switzerland
Providence Saint John's Health Center ( Site 3010)
🇺🇸Santa Monica, California, United States
NYU Clinical Cancer Center ( Site 3002)
🇺🇸New York, New York, United States
University of Colorado, Anschutz Cancer Pavilion ( Site 3012)
🇺🇸Aurora, Colorado, United States
Duke Cancer Institute ( Site 3005)
🇺🇸Durham, North Carolina, United States
Oregon Health & Science University ( Site 3013)
🇺🇸Portland, Oregon, United States
Melanoma Institute Australia ( Site 3402)
🇦🇺Wollstonecraft, New South Wales, Australia
Rabin Medical Center-Oncology ( Site 3705)
🇮🇱Petah-Tikva, Israel
Chaim Sheba Medical Center ( Site 3701)
🇮🇱Ramat Gan, Israel
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 3022)
🇺🇸Baltimore, Maryland, United States
Institut Claudius Regaud ( Site 3105)
🇫🇷Toulouse cedex 9, Haute-Garonne, France
Centre Hospitalier Lyon Sud ( Site 3102)
🇫🇷Pierre Benite, Rhone, France
HaEmek Medical Center ( Site 3703)
🇮🇱Afula, Israel
Rambam Health Care Campus-Oncology ( Site 3704)
🇮🇱Haifa, Israel
Tasman Oncology Research Pty Ltd ( Site 3403)
🇦🇺Southport, Queensland, Australia
A.P.H. Paris, Hopital Saint Louis ( Site 3107)
🇫🇷Paris, France