A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7566802 as a Single Agent and in Combination With Atezolizumab in Participants With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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This is a first-in-human Phase I, open-label, dose-escalation and expansion study designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamic, and preliminary anti-tumor activity of RO7566802 as a single agent and in combination with atezolizumab in participants with locally advanced, recurrent, or metastatic incurable solid tumor malignancies. Participants will be enrolled in 2 stages: dose escalation and expansion.

Official Title
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A Phase I, Open-Label, Multicenter, Dose-Escalation Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7566802 as a Single Agent and in Combination With Atezolizumab in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Locally Advanced Solid Tumors, Recurrent Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: RO7566802
* Drug: Atezolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 Life expectancy >=3 months, in the investigator's judgment Adequate hematologic and end-organ function Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy Measurable disease per RECIST v1.1 Disease that has progressed after at least one available standard therapy, and for which standard therapy has proven to be ineffective or intolerable or is considered inappropriate, or for which a clinical trial of an investigational agent is a recognized standard of care Tumor specimen availability, for certain cohorts Exclusion Criteria: Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to C1D1, with certain exceptions Active hepatitis B or C Active tuberculosis Positive test for HIV infection Administration of a live, attenuated vaccine (e.g., Flumist) within 4 weeks prior to RO7566802 infusion Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases Active or history of autoimmune disease Prior allogeneic stem cell or organ transplantation Uncontrolled tumor-related pain Significant cardiovascular disease Other protocol-defined inclusion/exclusion criteria may apply.

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort<br>Participants in successive cohorts will receive escalating doses of RO7566802, as an intravenous (IV) infusion on Day 1 of each 21-day cycle followed by RO7566802 in combination with a fixed dose of atezolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. | Drug: RO7566802<br>* RO7566802 solution for infusion will be administered as specified in each treatment arm.<br>Drug: Atezolizumab<br>* Atezolizumab solution for infusion will be administered as specified in each treatment arm.<br>* Other names: Tecentriq®;|
| Experimental: Dose Expansion Cohort<br>Participants with select solid tumors will receive a recommended dose of RO7566802, determined in Dose Escalation phase, as an IV infusion in combination with a fixed dose of atezolizumab, as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. | Drug: RO7566802<br>* RO7566802 solution for infusion will be administered as specified in each treatment arm.<br>Drug: Atezolizumab<br>* Atezolizumab solution for infusion will be administered as specified in each treatment arm.<br>* Other names: Tecentriq®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with DLTs |  | Cycle 1 Day 1 through 21 days after Cycle 2 Day 1 (Cycle length=21 days) (up to approximately 42 days) | 
| Percentage of Participants with Adverse Events (AEs) Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI CTCAE v5.0) |  | Up to approximately 39 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Serum Concentration Time Curve (AUC) of RO7566802 |  | Up to approximately 39 months | 
| Maximum Serum Concentration (Cmax) of RO7566802 |  | Up to approximately 39 months | 
| Minimum Serum Concentration (Cmin) of RO7566802 |  | Up to approximately 39 months | 
| Total Clearance (CL) of RO7566802 |  | Up to approximately 39 months | 
| Volume of Distribution at Steady State (Vss) of RO7566802 |  | Up to approximately 39 months | 
| Serum Concentration of Atezolizumab |  | Up to approximately 39 months | 
| Objective Response Rate as Determined by Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) |  | Up to approximately 39 months | 
| Percentage of Participants with Anti-Drug Antibodies (ADAs) to RO7566802 |  | From Baseline up to approximately 39 months |