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.

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Advanced Melanoma

Intervention / Treatment
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* Biological: Autogene cevumeran
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECISTv.1.1) After Randomization |  | The time from randomization to disease progression/death (up to approximately 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) According to RECISTv.1.1 After Randomization |  | Up to approximately 24 months | 
| Overall Survival (OS) After Randomization |  | 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 |  | 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 | 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. | From randomization up to approximately 24 months. | 
| Objective Response Rate (ORR) According to RECISTv.1.1 After Cross Over |  | Up 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) |