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A Study to Evaluate the Efficacy and Safety of Autogene Cevumeran (RO7198457) in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With Previously Untreated Advanced Melanoma.

Phase 2
Completed
Conditions
Advanced Melanoma
Interventions
Registration Number
NCT03815058
Lead Sponsor
Genentech, Inc.
Brief Summary

This study will evaluate the efficacy, safety, pharmacokinetics, and patient-reported outcomes (PROs) of autogene cevumeran (RO7198457) plus pembrolizumab compared with pembrolizumab alone in patients with previously untreated advanced melanoma.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
131
Inclusion Criteria
  • Histologically confirmed metastatic (recurrent or de novo Stage IV) or unresectable locally advanced (Stage IIIC or IIID) cutaneous, acral, or mucosal melanoma;
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  • Life expectancy >/= 12 weeks;
  • Adequate hematologic and end-organ function;
  • Naive to prior systemic anti-cancer therapy for advanced melanoma with some exceptions;
  • Tumor specimen availability;
  • Measurable disease per RECIST v1.1.

Exclusion criteria:

  • Ocular/uveal melanoma;
  • Any anti-cancer therapy with the exceptions as specified in the protocol;
  • Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases;
  • Previous splenectomy;
  • History of autoimmune disease;
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation;
  • Positive test for Human Immunodeficiency Virus (HIV) infection;
  • Active hepatitis B or C or tuberculosis;
  • Significant cardiovascular disease;
  • Known clinically significant liver disease.
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Safety Run-in Period: Autogene Cevumeran + PembrolizumabAutogene cevumeranParticipants will receive at least one cycle of 200 mg pembrolizumab monotherapy by intravenous (IV) infusion followed by 200 mg pembrolizumab IV infusion every 3 weeks (Q3W) plus a recommended dose of autogene cevumeran.
Randomized Period: Arm B: Autogene Cevumeran + PembrolizumabAutogene cevumeranParticipants will receive at least one cycle of 200 mg pembrolizumab monotherapy by IV infusion followed by 200 mg pembrolizumab IV infusion Q3W plus a recommended dose of autogene cevumeran.
Safety Run-in Period: Autogene Cevumeran + PembrolizumabPembrolizumabParticipants will receive at least one cycle of 200 mg pembrolizumab monotherapy by intravenous (IV) infusion followed by 200 mg pembrolizumab IV infusion every 3 weeks (Q3W) plus a recommended dose of autogene cevumeran.
Randomized Period: Arm A: PembrolizumabPembrolizumabParticipants will receive 200 mg pembrolizumab administered by IV infusion Q3W. Participants in Arm A have the option to cross over to combination treatment with autogene cevumeran plus pembrolizumab (Arm B) after confirmed disease progression.
Randomized Period: Arm B: Autogene Cevumeran + PembrolizumabPembrolizumabParticipants will receive at least one cycle of 200 mg pembrolizumab monotherapy by IV infusion followed by 200 mg pembrolizumab IV infusion Q3W plus a recommended dose of autogene cevumeran.
Primary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECISTv.1.1) After RandomizationThe time from randomization to disease progression/death (up to approximately 24 months)
Secondary Outcome Measures
NameTimeMethod
Objective Response Rate (ORR) According to RECISTv.1.1 After RandomizationUp to approximately 24 months
Overall Survival (OS) After RandomizationThe time from randomization to death from any cause (up to approximately 24 months).
Duration of Response (DOR) According to RECISTv.1.1 After RandomizationThe time from randomization up to approximately 24 months.
Mean Change in Global Health Status (GHS)/Health-related Quality of Life (HRQoL) Score After RandomizationFrom randomization up to approximately 24 months.

The 2-item GHS/HRQoL questionnaire of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ C30) uses a 7-point scale from 1=very poor to 7= excellent. Score range for GHS/HRQoL is 2-14. A negative change from baseline indicates deterioration in GHS.

Objective Response Rate (ORR) According to RECISTv.1.1 After Cross OverUp to 12 months from the time of cross-over
Percentage of Participants With Adverse Events (AEs)Baseline up to 90 days after the final dose of study drug (up to approximately 27 months)

Trial Locations

Locations (41)

Seattle Cancer Care Alliance

🇺🇸

Seattle, Washington, United States

Liverpool Hospital

🇦🇺

Liverpool, New South Wales, Australia

Atlanta Cancer Care

🇺🇸

Alpharetta, Georgia, United States

Case Western Research University

🇺🇸

Cleveland, Ohio, United States

Elbe Kliniken Stade-Buxtehude GmbH

🇩🇪

Buxtehude, Germany

Clinica Universidad de Navarra

🇪🇸

Pamplona, Navarra, Spain

City of Hope Comprehensive Cancer Center

🇺🇸

Duarte, California, United States

University of California San Diego Moores Cancer Center

🇺🇸

La Jolla, California, United States

UCSF Comprehensive Cancer Ctr

🇺🇸

San Francisco, California, United States

University of Colorado

🇺🇸

Denver, Colorado, United States

Cancer Specialists

🇺🇸

Jacksonville, Florida, United States

Moffitt McKinley Outpatient Center

🇺🇸

Tampa, Florida, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Massachusetts General Hospital.

🇺🇸

Boston, Massachusetts, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Oregon Health and Science University

🇺🇸

Portland, Oregon, United States

Sarah Cannon Research Institute / Tennessee Oncology

🇺🇸

Nashville, Tennessee, United States

Intermountain Surgical Oncology

🇺🇸

Murray, Utah, United States

Huntsman Cancer Institute

🇺🇸

Salt Lake City, Utah, United States

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

The Queen Elizabeth Hospital

🇦🇺

Woodville South, South Australia, Australia

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Alfred Hospital

🇦🇺

Melbourne, Victoria, Australia

St. John of God - Subiaco Hospital

🇦🇺

Subiaco, Western Australia, Australia

Antwerp University Hospital

🇧🇪

Edegem, Belgium

Sint Augustinus Wilrijk

🇧🇪

Wilrijk, Belgium

Universitatsklinikum Eppendorf

🇩🇪

Hamburg, Germany

Universitätsklinikum Heidelberg

🇩🇪

Heidelberg, Germany

Universitätsklinikum Koeln

🇩🇪

Koeln, Germany

Uni Schleswig-Holstein

🇩🇪

Lübeck, Germany

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR, Hautklinik und Poliklinik

🇩🇪

Mainz, Germany

Med. Fakultat Mannheim der Universitat Heidelberg

🇩🇪

Mannheim, Germany

Fachklinik Hornheide

🇩🇪

Muenster, Germany

Universitätshautk. Tübingen

🇩🇪

Tübingen, Germany

Instituto Oncológico Dr. Rosell

🇪🇸

Barcelona, Spain

Vall d?Hebron Institute of Oncology (VHIO), Barcelona

🇪🇸

Barcelona, Spain

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hospital General Universitario Gregorio Marañon

🇪🇸

Madrid, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Barts and The London

🇬🇧

London, United Kingdom

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