Substudy 02B: Safety and Efficacy of Pembrolizumab in Combination With Investigational Agents or Pembrolizumab Alone in Participants With First Line (1L) Advanced Melanoma (MK-3475-02B/KEYMAKER-U02)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04305054

Collaborator

(none)

315

Enrollment

Locations

Arms

117.1

Anticipated Duration (Months)

9.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Substudy 02B 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 02B is to evaluate the safety and efficacy of investigational treatment arms in participants with 1L advanced melanoma and to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/pembrolizumab monotherapy.

Condition or Disease	Intervention/Treatment	Phase
Melanoma	Biological: Pembrolizumab Biological: Vibostolimab Biological: Pembrolizumab/Quavonlimab Drug: Lenvatinib	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

315 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 02B

Actual Study Start Date :

Jul 1, 2020

Anticipated Primary Completion Date :

Apr 3, 2030

Anticipated Study Completion Date :

Apr 3, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab + Vibostolimab Participants will receive pembrolizumab intravenously (IV) plus vibostolimab IV at specified doses on specified days for a total treatment duration of up to approximately 2 years.	Biological: Pembrolizumab Administered via IV infusion at a specified dose on specified days Other Names: MK-3475 KEYTRUDA® Biological: Vibostolimab Administered via IV infusion at a specified dose on specified days Other Names: MK-7684
Active Comparator: Pembrolizumab Participants will receive pembrolizumab IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.	Biological: Pembrolizumab Administered via IV infusion at a specified dose on specified days Other Names: MK-3475 KEYTRUDA®
Experimental: Coformulation Pembrolizumab/Quavonlimab Participants will receive coformulation of pembrolizumab and quavonlimab (MK-1308A) IV at a specified dose on specified days for a total treatment duration of up to approximately 2 years.	Biological: Pembrolizumab Administered via IV infusion at a specified dose on specified days Other Names: MK-3475 KEYTRUDA® Biological: Pembrolizumab/Quavonlimab Administered via IV infusion at a specified dose on specified days Other Names: MK-1308A
Experimental: Coformulation Pembrolizumab/Quavonlimab + Lenvatinib Participants will receive coformulation of pembrolizumab and quavonlimab IV plus lenvatinib orally at specified doses on specified days for a total treatment duration of up to approximately 2 years.	Biological: Pembrolizumab Administered via IV infusion at a specified dose on specified days Other Names: MK-3475 KEYTRUDA® Biological: Pembrolizumab/Quavonlimab Administered via IV infusion at a specified dose on specified days Other Names: MK-1308A Drug: Lenvatinib Administered via oral capsule at a specified dose on specified days Other Names: MK-7902 E7080 LENVIMA®

Outcome Measures

Primary Outcome Measures

Percentage of participants who experience an adverse event (AE) [Up to ~28 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 ~24 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.
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) [Up to ~30 months]
ORR is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by blinded independent central review (BICR). 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.

Secondary Outcome Measures

Duration of Response (DOR) per RECIST 1.1 [Up to ~30 months]
For participants in the analysis population who demonstrate a confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to RECIST 1.1 as assessed by BICR. 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Has histologically or cytologically confirmed melanoma
Has unresectable Stage III or Stage IV melanoma, not amenable to local therapy
Has been untreated for advanced disease
Has provided a tumor biopsy
Male participants 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 lenvatinib; 7 days after lenvatinib is stopped, if participants are on pembrolizumab, pembrolizumab/quavonlimab, vibostolimab or a combination of the aforementioned drugs, no additional male contraception measures are needed
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, pembrolizumab/quavonlimab, vibostolimab, or 30 days after the last dose of lenvatinib, 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 and Grade 2 neuropathy)

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 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 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 a known psychiatric or substance abuse disorder that would interfere with requirements of the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Angeles Clinic and Research Institute ( Site 2009)	Los Angeles	California	United States	90025
2	UCLA Hematology & Oncology ( Site 2004)	Los Angeles	California	United States	90095
3	Providence Saint John's Health Center ( Site 2010)	Santa Monica	California	United States	90404
4	University of Colorado, Anschutz Cancer Pavilion ( Site 2012)	Aurora	Colorado	United States	80045
5	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Site 2022)	Baltimore	Maryland	United States	21231
6	NYU Clinical Cancer Center ( Site 2002)	New York	New York	United States	10016
7	Duke Cancer Institute ( Site 2005)	Durham	North Carolina	United States	27710
8	Oregon Health & Science University ( Site 2013)	Portland	Oregon	United States	97239
9	University of Pennsylvania Abramson Cancer Center ( Site 2008)	Philadelphia	Pennsylvania	United States	19104
10	West Cancer Center - East Campus ( Site 2014)	Germantown	Tennessee	United States	38138
11	Inova Schar Cancer Institute ( Site 2011)	Fairfax	Virginia	United States	22031
12	Calvary Mater Newcastle-Medical Oncology ( Site 2404)	Waratah	New South Wales	Australia	2298
13	Melanoma Institute Australia ( Site 2402)	Wollstonecraft	New South Wales	Australia	2065
14	Tasman Oncology Research Pty Ltd ( Site 2403)	Southport	Queensland	Australia	4120
15	Fiona Stanley Hospital ( Site 2401)	Murdoch	Western Australia	Australia	6150
16	Hopital La Timone ( Site 2103)	Marseille	Bouches-du-Rhone	France	13005
17	CHU de Bordeaux- Hopital Saint Andre ( Site 2108)	Bordeaux	Gironde	France	33075
18	Gustave Roussy ( Site 2101)	Villejuif	Ile-de-France	France	94800
19	C.H. Lyon Sud ( Site 2102)	Pierre Benite	Rhone	France	69495
20	A.P.H. Paris, Hopital Saint Louis ( Site 2107)	Paris		France	75010
21	HaEmek Medical Center ( Site 2703)	Afula		Israel	1834111
22	Rambam Health Care Campus-Oncology ( Site 2704)	Haifa		Israel	3109601
23	Hadassah Ein Karem Jerusalem ( Site 2702)	Jerusalem		Israel	9112001
24	Rabin Medical Center-Oncology ( Site 2705)	Petah-Tikva		Israel	4941492
25	Chaim Sheba Medical Center ( Site 2701)	Ramat Gan		Israel	5265601
26	Istituto Oncologico Veneto IRCCS ( Site 2355)	Padova	Veneto	Italy	35128
27	Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 2399)	Milano		Italy	20133
28	Istituto Europeo di Oncologia ( Site 2301)	Milano		Italy	20141
29	Istituto Nazionale Tumori Fondazione Pascale ( Site 2302)	Napoli		Italy	80131
30	Policlinico Le Scotte - A.O. Senese ( Site 2377)	Siena		Italy	53100
31	CANCERCARE LANGENHOVEN DRIVE ONCOLOGY CENTRE-Clinical Trials Unit ( Site 2865)	Port Elizabeth	Eastern Cape	South Africa	6055
32	Cape Town Oncology Trials ( Site 2864)	Cape Town	Western Cape	South Africa	7570
33	CHUV Centre Hospitalier Universitaire Vaudois ( Site 2602)	Lausanne	Vaud	Switzerland	1011
34	Universitaetsspital Zuerich ( Site 2601)	Zuerich Flughafen	Zurich	Switzerland	8058