Clinical trial NCT04303169: 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)
Official 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Melanoma
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death ligand 1 (PD-L1, PDL1)
Coxsackievirus A21
Intracellular Adhesion Molecule-1 (ICAM-1)
T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine receptor motif domains (TIGIT)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-03-10
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

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

Primary outcomes:
measure: Percentage of participants who experience an adverse event (AE)
timeFrame: Up to ~16 months
measure: Percentage of participants who discontinue study treatment due to an AE
timeFrame: Up to ~12 months
measure: Pathological complete response (pCR) rate
timeFrame: Up to ~1.5 months
Secondary outcomes:
measure: Near pathological complete response (near pCR) rate
timeFrame: Up to ~1.5 months
measure: Pathological partial response (pPR) rate
timeFrame: Up to ~1.5 months
measure: Recurrence-free survival (RFS)
timeFrame: Up to ~60 months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: The Angeles Clinic and Research Institute ( Site 3009)
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Health Center ( Site 3010)
state: California
city: Aurora
country: United States
facility: University of Colorado, Anschutz Cancer Pavilion ( Site 3012)
state: Colorado
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 3022)
state: Maryland
city: New York
country: United States
facility: NYU Clinical Cancer Center ( Site 3002)
state: New York
city: Durham
country: United States
facility: Duke Cancer Institute ( Site 3005)
state: North Carolina
city: Columbus
country: United States
facility: Martha Morehouse Tower ( Site 3020)
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University ( Site 3013)
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center ( Site 3008)
state: Pennsylvania
city: Germantown
country: United States
facility: West Cancer Center - East Campus ( Site 3014)
state: Tennessee
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute ( Site 3011)
state: Virginia
city: Wollstonecraft
country: Australia
facility: Melanoma Institute Australia ( Site 3402)
state: New South Wales
city: Southport
country: Australia
facility: Tasman Oncology Research Pty Ltd ( Site 3403)
state: Queensland
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital ( Site 3401)
state: Western Australia
city: Marseille
country: France
facility: Hopital La Timone ( Site 3103)
state: Bouches-du-Rhone
city: Toulouse cedex 9
country: France
facility: Institut Claudius Regaud ( Site 3105)
state: Haute-Garonne
city: Villejuif
country: France
facility: Gustave Roussy ( Site 3101)
state: Ile-de-France
city: Pierre Benite
country: France
facility: Centre Hospitalier Lyon Sud ( Site 3102)
state: Rhone
city: Paris
country: France
facility: A.P.H. Paris, Hopital Saint Louis ( Site 3107)
city: Afula
country: Israel
facility: HaEmek Medical Center ( Site 3703)
city: Haifa
country: Israel
facility: Rambam Health Care Campus-Oncology ( Site 3704)
city: Jerusalem
country: Israel
facility: Hadassah Ein Karem Jerusalem ( Site 3702)
city: Petah-Tikva
country: Israel
facility: Rabin Medical Center-Oncology ( Site 3705)
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center ( Site 3701)
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia ( Site 3301)
city: Siena
country: Italy
facility: Policlinico Le Scotte - A.O. Senese ( Site 3377)
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 3603)
state: Geneve
city: Lausanne
country: Switzerland
facility: CHUV Centre Hospitalier Universitaire Vaudois ( Site 3602)
state: Vaud
city: Zuerich Flughafen
country: Switzerland
facility: Universitaetsspital Zuerich ( Site 3601)
state: Zurich
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: