An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-Risk Melanoma (KEYNOTE-942)

Sponsor

ModernaTX, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03897881

Collaborator

Merck Sharp & Dohme LLC (Industry)

157

Enrollment

Locations

Arms

62.4

Anticipated Duration (Months)

7.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence free survival (RFS) compared to pembrolizumab alone in participants with complete resection of cutaneous melanoma and a high risk of recurrence.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: mRNA-4157 Biological: Pembrolizumab	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

157 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Masking Description:

Open Label

Primary Purpose:

Treatment

Official Title:

A Phase 2 Randomized Study of Adjuvant Immunotherapy With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab Versus Pembrolizumab Alone After Complete Resection of High-Risk Melanoma (KEYNOTE- 942)

Actual Study Start Date :

Jul 18, 2019

Anticipated Primary Completion Date :

Sep 29, 2024

Anticipated Study Completion Date :

Sep 29, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: mRNA-4157 and Pembrolizumab Participants will receive up to 9 doses of mRNA-4157 (every 21 days). Participants may continue on pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.	Biological: mRNA-4157 Personalized cancer vaccine Biological: Pembrolizumab Intravenous infusion
Active Comparator: Pembrolizumab Participants will receive pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.	Biological: Pembrolizumab Intravenous infusion

Arm

Intervention/Treatment

Experimental: mRNA-4157 and Pembrolizumab

Participants will receive up to 9 doses of mRNA-4157 (every 21 days). Participants may continue on pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.

Biological: mRNA-4157

Personalized cancer vaccine

Biological: Pembrolizumab

Intravenous infusion

Active Comparator: Pembrolizumab

Participants will receive pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner.

Biological: Pembrolizumab

Intravenous infusion

Outcome Measures

Primary Outcome Measures

Recurrence-Free Survival (RFS), Assessed Using Radiological Imaging [Up to 3 years]
RFS is defined as the time between the date of first dose of pembrolizumab and the date of recurrence (local, regional, or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first.

Secondary Outcome Measures

Distant Metastasis-Free Survival (DMFS), Assessed Using Radiological Imaging [Up to 3 years]
DMFS is defined as the time between the date of first dose of pembrolizumab and the date of the first distant metastasis or the date of death (whatever the cause), whichever occurs first.
Number of Participants With Adverse Events (AEs) [Baseline through 100 days after last mRNA-4157 dose (for mRNA-4157 and Pembrolizumab combination arm) and up to 90 days after last pembrolizumab dose (for Pembrolizumab only arm) (up to a total of 3 years for both arms)]
Number of Participants Who Discontinued Due to AEs [Baseline through 100 days after last mRNA-4157 dose (for mRNA-4157 and Pembrolizumab combination arm) and up to 90 days after last pembrolizumab dose (for Pembrolizumab only arm) (up to a total of 3 years for both arms)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Resectable cutaneous melanoma metastatic to a lymph node and at high risk of recurrence
Complete resection within 13 weeks prior to the first dose of pembrolizumab
Disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases
Has an formalin fixed paraffin embedded (FFPE) tumor sample available suitable for sequencing
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
Normal organ and marrow function reported at screening

Key Exclusion Criteria:

Prior malignancy, unless no evidence of that disease for at least 5 years prior to study entry
Prior systemic anti-cancer treatment (except surgery and interferon for thick primary melanomas. Radiotherapy after lymph node dissection is permitted)
Live vaccine within 30 days prior to the first dose of pembrolizumab
Transfusion of blood or administration of colony stimulating factors within 2 weeks of the screening blood sample
Active autoimmune disease
Immunodeficiency, systemic steroid therapy, or any other immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
Solid organ or allogeneic bone marrow transplant
Pneumonitis or a history of (noninfectious) pneumonitis that required steroids
Prior interstitial lung disease
Clinically significant heart failure
Known history of human immunodeficiency virus (HIV)
Known active hepatitis B or C
Active infection requiring treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona	Tucson	Arizona	United States	85719
2	California Pacific Medical Center Research Institute -CPMCRI	San Francisco	California	United States	94115
3	Angeles Clinic and Research Institute	Santa Monica	California	United States	90404
4	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
5	Smilow Cancer Center at Yale New Haven Hospital	New Haven	Connecticut	United States	06520
6	Lombardi Cancer Center	Washington	District of Columbia	United States	20007
7	Orlando Health UF Health Cancer Center	Orlando	Florida	United States	32806
8	UPMC Hillman Cancer Center	Chicago	Illinois	United States	60637
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
11	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
12	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
13	NYU Langone Medical Center	New York	New York	United States	10016
14	Providence Cancer Institute	Portland	Oregon	United States	97213
15	Oregon Health & Science University	Portland	Oregon	United States	97239
16	Sarah Cannon Cancer Center	Nashville	Tennessee	United States	37203
17	Texas Oncology PA	Dallas	Texas	United States	75246
18	Melanoma Institute Australia	North Sydney	New South Wales	Australia	2060
19	Westmead Hospital	Westmead	New South Wales	Australia	2145
20	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
21	Affinity Clinical Research	Murdoch	Western Australia	Australia	6150
22	St John of God Hospital Subiaco	Subiaco	Western Australia	Australia	6008