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. (IMCODE001)

A Phase II, Open-Label, Multicenter, Randomized Study of the Efficacy and Safety of RO7198457 in Combination With Pembrolizumab Versus Pembrolizumab in Patients With Previously Untreated Advanced Melanoma

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.

Study Overview

• Status: Completed
• Conditions: Advanced Melanoma
• Intervention / Treatment: Drug: Pembrolizumab; Biological: Autogene cevumeran

• Study Type: Interventional
• Enrollment (Actual): 131
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3181
      • Alfred Hospital
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • St. John of God - Subiaco Hospital
• Belgium
  • Edegem, Belgium, 2650
    • Antwerp University Hospital
  • Wilrijk, Belgium, 2610
    • ZAS Sint Augustinus Wilrijk
• Germany
  • Buxtehude, Germany, 21614
    • Elbe Kliniken Stade-Buxtehude GmbH
  • Cologne, Germany, 50937
    • Universitatsklinikum Koeln
  • Hamburg, Germany, 20246
    • Universitätsklinikum Eppendorf
  • Heidelberg, Germany, 69120
    • Universitätsklinikum Heidelberg
  • Lübeck, Germany, 23562
    • Uni Schleswig-Holstein
  • Mainz, Germany, 55131
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR, Hautklinik und Poliklinik
  • Mannheim, Germany, 68167
    • Med. Fakultat Mannheim der Universitat Heidelberg
  • Münster, Germany, 48157
    • Fachklinik Hornheide
  • Tübingen, Germany, 72076
    • Universitätshautk. Tübingen
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Barcelona, Spain, 08028
    • Instituto Oncológico Dr. Rosell
  • Barcelona, Spain, 08035
    • Vall d?Hebron Institute of Oncology (VHIO), Barcelona
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 280146
    • Hospital Universitario La Paz
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universidad de Navarra
• United Kingdom
  • London, United Kingdom, EC1M 6BQ
    • Barts and The London
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92037
      • University Of California San Diego Moores Cancer Center
    • San Francisco, California, United States, 94115
      • UCSF Comprehensive Cancer Ctr
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Cancer Specialists
    • Tampa, Florida, United States, 33612
      • Moffitt McKinley Outpatient Center
  • Georgia
    • Alpharetta, Georgia, United States, 30005
      • Atlanta Cancer Care
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital.
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University
  • Ohio
    • Cleveland, Ohio, United States, 44106-5067
      • Case Western Research University
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute / Tennessee Oncology
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Surgical Oncology
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22906
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Safety Run-in Period: Autogene Cevumeran + Pembrolizumab; 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.	Drug: Pembrolizumab; Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W.; Other Names: Keytruda; Biological: Autogene cevumeran; Participants will receive a recommended dose of autogene cevumeran administered by IV infusion at protocol-defined intervals.; Other Names: RO7198457
Active Comparator: Randomized Period: Arm A: Pembrolizumab; 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; Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W.; Other Names: Keytruda
Experimental: Randomized Period: Arm B: Autogene Cevumeran + Pembrolizumab; 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.	Drug: Pembrolizumab; Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W.; Other Names: Keytruda; Biological: Autogene cevumeran; Participants will receive a recommended dose of autogene cevumeran administered by IV infusion at protocol-defined intervals.; Other Names: RO7198457

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) According to RECIST V.1.1 After Randomization	ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off to the nearest whole number.	Up to approximately 60 months
Overall Survival (OS) After Randomization	OS was defined as the time from randomization to death from any cause. KM method was used to estimate the median OS.	From randomization to death (up to approximately 63 months)
Duration of Response (DOR) According to RECIST V.1.1 After Randomization	DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD or death from any cause, whichever occurred first, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the 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 mm. DOR was estimated using the KM methodology.	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)	EORTC QLQ-C30 consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding GHS (Question 29: GHS; "How would you rate your overall health during the past week?") and QoL (Question 30: QoL; "How would you rate your overall quality of life during the past week?") and were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized. Scores range from 0-100. A higher score indicates a better QoL.	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	ORR was defined as the percentage of participants with a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR.	Up to 54.7 months
Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.	Baseline up to 90 days after the final dose of study drug (Safety run-in and randomized stage: up to 32 months; Cross-over stage: up to 24 months)

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: BioNTech SE
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Actual): January 21, 2025
• Study Completion (Actual): January 21, 2025

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 23, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: GO40558; 2018-001773-24 (EudraCT Number); 2023-507389-15-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No