A Study of Multiple Doses of RO7247669 in Participants With Previously Untreated Unresectable or Metastatic Melanoma

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy, safety, pharmacokinetics (PK), and pharmacodynamics of two dose levels of RO7247669 in participants with unresectable or metastatic melanoma to select the recommended dose for further development.

Official Title
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A Randomized, Open-Label, Multicenter, Phase II Study of Multiple Doses of RO7247669 in Participants With Previously Untreated Unresectable or Metastatic Melanoma

Conditions
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Melanoma

Intervention / Treatment
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* Drug: RO7247669


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed unresectable or metastatic melanoma, per the American Joint Committee on Cancer (AJCC) staging system (unresectable Stage III or Stage IV) Radiologically measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 Known v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status Adequate cardiovascular, hematological, hepatic and renal function Willingness to abide by contraceptive measures for the duration of the study Participants must have known PD-L1 status Exclusion Criteria: Pregnancy, lactation, or breastfeeding Known hypersensitivity to any of the components of RO7247669 Participants must not have ocular melanoma Symptomatic central nervous system (CNS) metastases Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic, or other infection or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization within 28 days prior to randomization Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study Active or history of autoimmune disease or immune deficiency with some exceptions Prior systemic anticancer therapy for unresectable or metastatic melanoma Prior anticancer therapy with any-immunomodulatory agents including CPIs (such as anti-programmed death-ligand 1[PD-L1]/PD-1 and anti-cytotoxic T lymphocyte-associated antigen [CTLA-4]) with some exceptions if used as prior adjuvant or neoadjuvant melanoma therapies Prior treatment with anti-LAG3 therapy

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: Low dose every three weeks (Q3W)<br>Participants will receive RO7247669 Q3W until loss of clinical benefit, unacceptable toxicity, or a maximum of 24 months. | Drug: RO7247669<br>* Participants will receive intravenous (IV) RO7247669 Q3W<br>|
| Experimental: High dose Q3W<br>Participants will receive RO7247669 Q3W until loss of clinical benefit, unacceptable toxicity, or a maximum of 24 months. | Drug: RO7247669<br>* Participants will receive intravenous (IV) RO7247669 Q3W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) |  | From randomization to the first occurrence of progression or death during the treatment period or within 60 days of the last tumor assessment after treatment discontinuation from any cause, whichever occurs first (up to 25 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events |  | Up to 25 months | 
| Objective response rate (ORR) |  | Up to 25 months | 
| Disease control rate (DCR) |  | Up to 25 months | 
| Duration of response (DOR) |  | From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 25 months) | 
| Serum concentration of RO7247669 |  | Up to 25 months | 
| Percentage of participants with anti-drug antibodies (ADAs) |  | Baseline up to 25 months | 
| Change from baseline in the number and activation status of peripheral blood immune cells |  | Baseline up to 25 months | 
| Change from baseline in the number and activation of immune cells in the tumor microenvironment |  | Baseline to Cycle 2 Day 9 (cycle = 21 days) |