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)

Melanoma Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04303169
• Other study ID #: 3475-02C
• Secondary ID: MK-3475-02CKEYMA
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: June 26, 2020
• Est. completion date: April 3, 2030

Study information

• Verified date: January 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 90
• Est. completion date: April 3, 2030
• Est. primary completion date: April 3, 2030
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Melanoma

Intervention

Biological:
• Pembrolizumab
Administered via IV infusion at a specified dose on specified days
• Vibostolimab
Administered via IV infusion at a specified dose on specified days
• Gebasaxturev
Administered via IT injection at a specified dose on specified days
• MK-4830
Administered via IV infusion at a specified dose on specified days
• Favezelimab + Pembrolizumab
Administered via IV infusion at a specified dose on specified days

Drug:
• ATRA
Administered via oral capsules at a specified dose on specified days

Locations

Country	Name	City	State
Australia	Fiona Stanley Hospital ( Site 3401)	Murdoch	Western Australia
Australia	Tasman Oncology Research Pty Ltd ( Site 3403)	Southport	Queensland
Australia	Melanoma Institute Australia ( Site 3402)	Wollstonecraft	New South Wales
France	Hopital La Timone ( Site 3103)	Marseille	Bouches-du-Rhone
France	A.P.H. Paris, Hopital Saint Louis ( Site 3107)	Paris
France	Centre Hospitalier Lyon Sud ( Site 3102)	Pierre Benite	Rhone
France	Institut Claudius Regaud ( Site 3105)	Toulouse cedex 9	Haute-Garonne
France	Gustave Roussy ( Site 3101)	Villejuif	Ile-de-France
Israel	HaEmek Medical Center ( Site 3703)	Afula
Israel	Rambam Health Care Campus-Oncology ( Site 3704)	Haifa
Israel	Hadassah Ein Karem Jerusalem ( Site 3702)	Jerusalem
Israel	Rabin Medical Center-Oncology ( Site 3705)	Petah-Tikva
Israel	Chaim Sheba Medical Center ( Site 3701)	Ramat Gan
Italy	Istituto Europeo di Oncologia ( Site 3301)	Milano
Italy	Policlinico Le Scotte - A.O. Senese ( Site 3377)	Siena
Switzerland	Hôpitaux Universitaires de Genève (HUG)-Oncology ( Site 3603)	Genève	Geneve
Switzerland	CHUV Centre Hospitalier Universitaire Vaudois ( Site 3602)	Lausanne	Vaud
Switzerland	Universitaetsspital Zuerich ( Site 3601)	Zuerich Flughafen	Zurich
United States	University of Colorado, Anschutz Cancer Pavilion ( Site 3012)	Aurora	Colorado
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 3022)	Baltimore	Maryland
United States	Martha Morehouse Tower ( Site 3020)	Columbus	Ohio
United States	Duke Cancer Institute ( Site 3005)	Durham	North Carolina
United States	Inova Schar Cancer Institute ( Site 3011)	Fairfax	Virginia
United States	West Cancer Center - East Campus ( Site 3014)	Germantown	Tennessee
United States	The Angeles Clinic and Research Institute ( Site 3009)	Los Angeles	California
United States	NYU Clinical Cancer Center ( Site 3002)	New York	New York
United States	University of Pennsylvania Abramson Cancer Center ( Site 3008)	Philadelphia	Pennsylvania
United States	Oregon Health & Science University ( Site 3013)	Portland	Oregon
United States	Providence Saint John's Health Center ( Site 3010)	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  France,  Israel,  Italy,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to ~16 months
Primary	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.	Up to ~12 months
Primary	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.	Up to ~1.5 months
Secondary	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.	Up to ~1.5 months
Secondary	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.	Up to ~1.5 months
Secondary	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.	Up to ~60 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary