NCT03815058

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
131

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Dec 2018

Longer than P75 for phase_2

Geographic Reach
6 countries

41 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 21, 2018

Completed
17 days until next milestone

First Submitted

Initial submission to the registry

January 7, 2019

Completed
17 days until next milestone

First Posted

Study publicly available on registry

January 24, 2019

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 21, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 21, 2025

Completed
1 year until next milestone

Results Posted

Study results publicly available

January 30, 2026

Completed
Last Updated

January 30, 2026

Status Verified

January 1, 2026

Enrollment Period

6.1 years

First QC Date

January 7, 2019

Results QC Date

January 14, 2026

Last Update Submit

January 14, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) After Randomization

    PFS was defined as the time from randomization to the first documented PD as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (KM) method was used to estimate median PFS.

    From randomization to PD or death (up to approximately 60 months)

Secondary Outcomes (6)

  • Objective Response Rate (ORR) According to RECIST V.1.1 After Randomization

    Up to approximately 60 months

  • Overall Survival (OS) After Randomization

    From randomization to death (up to approximately 63 months)

  • Duration of Response (DOR) According to RECIST V.1.1 After Randomization

    Up to approximately 60 months

  • Change From Baseline in Global Health Status (GHS)/Health-related Quality of Life (HRQoL) Score Assessed by European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire (EORTC QLQ-C30)

    Baseline, Day 1 of Cycles 1 to 34, time of first PD, time to last dose, treatment discontinuation and study drug completion (up to approximately 29 months) (1 cycle = 21 days)

  • ORR According to RECIST V.1.1 After Crossover

    Up to 54.7 months

  • +1 more secondary outcomes

Study Arms (3)

Safety Run-in Period: Autogene Cevumeran + Pembrolizumab

EXPERIMENTAL

Participants 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.

Biological: Autogene cevumeranDrug: Pembrolizumab

Randomized Period: Arm A: Pembrolizumab

ACTIVE COMPARATOR

Participants 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.

Drug: Pembrolizumab

Randomized Period: Arm B: Autogene Cevumeran + Pembrolizumab

EXPERIMENTAL

Participants 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.

Biological: Autogene cevumeranDrug: Pembrolizumab

Interventions

Participants will receive a recommended dose of autogene cevumeran administered by IV infusion at protocol-defined intervals.

Also known as: RO7198457
Randomized Period: Arm B: Autogene Cevumeran + PembrolizumabSafety Run-in Period: Autogene Cevumeran + Pembrolizumab

Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W.

Also known as: Keytruda
Randomized Period: Arm A: PembrolizumabRandomized Period: Arm B: Autogene Cevumeran + PembrolizumabSafety Run-in Period: Autogene Cevumeran + Pembrolizumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (41)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92037, United States

Location

UCSF Comprehensive Cancer Ctr

San Francisco, California, 94115, United States

Location

University of Colorado

Denver, Colorado, 80262, United States

Location

Cancer Specialists

Jacksonville, Florida, 32256, United States

Location

Moffitt McKinley Outpatient Center

Tampa, Florida, 33612, United States

Location

Atlanta Cancer Care

Alpharetta, Georgia, 30005, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital.

Boston, Massachusetts, 02114, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Case Western Research University

Cleveland, Ohio, 44106-5067, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Intermountain Surgical Oncology

Murray, Utah, 84107, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22906, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

St. John of God - Subiaco Hospital

Subiaco, Western Australia, 6008, Australia

Location

Antwerp University Hospital

Edegem, 2650, Belgium

Location

ZAS Sint Augustinus Wilrijk

Wilrijk, 2610, Belgium

Location

Elbe Kliniken Stade-Buxtehude GmbH

Buxtehude, 21614, Germany

Location

Universitätsklinikum Koeln

Cologne, 50937, Germany

Location

Universitatsklinikum Eppendorf

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Uni Schleswig-Holstein

Lübeck, 23562, Germany

Location

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

Mainz, 55131, Germany

Location

Med. Fakultat Mannheim der Universitat Heidelberg

Mannheim, 68167, Germany

Location

Fachklinik Hornheide

Münster, 48157, Germany

Location

Universitätshautk. Tübingen

Tübingen, 72076, Germany

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Instituto Oncológico Dr. Rosell

Barcelona, 08028, Spain

Location

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

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28007, Spain

Location

Hospital Universitario La Paz

Madrid, 280146, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Barts and The London

London, EC1M 6BQ, United Kingdom

Location

MeSH Terms

Interventions

pembrolizumab

Results Point of Contact

Title
Medical Communications
Organization
Hoffmann-La Roche

Study Officials

  • Clinical Trials

    Hoffmann-La Roche

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 7, 2019

First Posted

January 24, 2019

Study Start

December 21, 2018

Primary Completion

January 21, 2025

Study Completion

January 21, 2025

Last Updated

January 30, 2026

Results First Posted

January 30, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will share

Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).

Locations