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)

• ClinicalTrials.gov Identifier: NCT03815058
• Recruitment Status: Active, not recruiting
• First Posted: January 24, 2019
• Last Update Posted: April 26, 2024
• Sponsor: Genentech, Inc.
• Collaborator: BioNTech SE
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: January 7, 2019
• First Posted Date: January 24, 2019
• Last Update Posted Date: April 26, 2024
• Actual Study Start Date: January 8, 2019
• Estimated Primary Completion Date: October 30, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 3, 2019): Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECISTv.1.1) After Randomization [ Time Frame: The time from randomization to disease progression/death (up to approximately 24 months) ]

Original Primary Outcome Measures (submitted: January 23, 2019)

• Progression-free Survival (PFS) in RO7198457 + pembrolizumab treated participants compared with pembrolizumab-only participants [ Time Frame: The time from randomization to disease progression/death (up to approximately 24 months) ]
  According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Objective Response Rate (ORR) in RO7198457 + pembrolizumab treated participants compared with pembrolizumab-only participants [ Time Frame: Proportion of participants with Complete Response (CR) or Partial Response (PR) (up to approximately 24 months) ]
  According to RECIST v1.1

Current Secondary Outcome Measures (submitted: November 15, 2023)

• Objective Response Rate (ORR) According to RECISTv.1.1 After Randomization [ Time Frame: Up to approximately 24 months ]
• Overall Survival (OS) After Randomization [ Time Frame: The time from randomization to death from any cause (up to approximately 24 months). ]
• Duration of Response (DOR) According to RECISTv.1.1 After Randomization [ Time Frame: The time from randomization up to approximately 24 months. ]
• Mean Change in Global Health Status (GHS)/Health-related Quality of Life (HRQoL) Score After Randomization [ Time Frame: From 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 Over [ Time Frame: Up to 12 months from the time of cross-over ]
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Baseline up to 90 days after the final dose of study drug (up to approximately 27 months) ]

Original Secondary Outcome Measures (submitted: January 23, 2019)

• Overall Survival (OS) in RO7198457 + pembrolizumab treated participants compared with pembrolizumab-only participants [ Time Frame: The time from randomization to death from any cause (up to approximately 24 months). ]
  Survival follow-up will be collected approximately every 3 months until death, loss to follow-up, withdrawal of consent, whichever occurs first.
• Duration of Response (DOR) in RO7198457 + pembrolizumab treated participants compared with pembrolizumab-only participants [ Time Frame: The time from randomization up to approximately 24 months. ]
  Determined by the Investigator according to RECIST v1.1
• Mean change in health-related quality of life (HRQoL) scores in RO7198457 + pembrolizumab treated participants compared with pembrolizumab-only participants [ Time Frame: The time from randomization up to approximately 24 months. ]
• Percentage of Participants with Objective Response of CR or PR following cross-over from pembrolizumab monotherapy to combination therapy [ Time Frame: Up to 12 months from the time of cross-over ]
  According to RECIST v1.1
• Incidence and Severity of Adverse Events (AEs) [ Time Frame: Baseline Up to 90 days after the final dose of study drug ]
  According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.
• Official Title: 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Melanoma

Intervention

• Biological: Autogene cevumeran
  Participants will receive a recommended dose of autogene cevumeran administered by IV infusion at protocol-defined intervals.
  Other Name: RO7198457
• Drug: Pembrolizumab
  Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W.
  Other Name: Keytruda

Study Arms

• 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.
  Interventions:

  • Biological: Autogene cevumeran
  • Drug: Pembrolizumab
• 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.
  Intervention: Drug: Pembrolizumab
• 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.
  Interventions:

  • Biological: Autogene cevumeran
  • Drug: Pembrolizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: February 23, 2022): 131
• Original Estimated Enrollment (submitted: January 23, 2019): 132
• Estimated Study Completion Date: October 30, 2025
• Estimated Primary Completion Date: October 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Germany, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03815058
• Other Study ID Numbers: GO40558; 2018-001773-24 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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).

• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: BioNTech SE

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Genentech, Inc.
• Verification Date: April 2024