A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7502175 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 study to evaluate the safety, tolerability, pharmacokinetics (PK), and anti-tumor activity of RO7502175 when administered as a single agent and in combination with atezolizumab in adult participants with locally advanced or metastatic solid tumors, including non-small-cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), melanoma, triple-negative breast cancer (TNBC), esophageal cancer, gastric cancer, cervical cancer, urothelial carcinoma (UC), clear cell renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). Participants will be enrolled in 2 stages: dose escalation and dose expansion.

Official Title
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A Phase Ia/Ib, Open Label, Multicenter, Dose-escalation Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7502175 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 or Metastatic Solid Tumors, NSCLC, HNSCC, Melanoma, TNBC, Esophageal Cancer, Gastric Cancer, Cervical Cancer, Urothelial Carcinoma, Clear Cell RCC, HCC

Intervention / Treatment
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* Drug: RO7502175
* Drug: Atezolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Life expectancy at least 12 weeks Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Measurable disease according to Response Evaluation criteria in Solid Tumors (RECIST) Version 1.1 Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy Tumor Specimen availability Exclusion Criteria: Pregnant or breastfeeding, or intending to become pregnant during the study or within 5 months after the final dose of study treatment Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment Active hepatitis B or C or tuberculosis Positive test for human immunodeficiency virus (HIV) infection Acute or chronic active Epstein-Barr virus (EBV) infection at screening Administration of a live, attenuated vaccine (e.g., FluMist) within 4 weeks before first RO7502175 infusion Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases Active or history of autoimmune disease Prior allogeneic stem cell or organ transplantation

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: Phase Ia: Dose Escalation<br>Participants in successive cohorts will receive escalating doses of RO7502175, as an intravenous (IV) infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. | Drug: RO7502175<br>* RO7502175 will be administered as per the schedules specified in the respective arms.<br>|
| Experimental: Phase Ia: Expansion<br>Participants with select solid tumors will receive a recommended dose of RO7502175, determined in Phase Ia Dose Escalation phase as an IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. | Drug: RO7502175<br>* RO7502175 will be administered as per the schedules specified in the respective arms.<br>|
| Experimental: Phase Ib: Dose Escalation<br>Participants in successive cohorts will receive escalating doses of RO7502175, 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: RO7502175<br>* RO7502175 will be administered as per the schedules specified in the respective arms.<br>Drug: Atezolizumab<br>* Atezolizumab will be administered as per the schedules specified in the respective arms.<br>|
| Experimental: Phase Ib: Expansion<br>Participants with select solid tumors will receive a recommended dose of RO7502175, determined in Phase Ib 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: RO7502175<br>* RO7502175 will be administered as per the schedules specified in the respective arms.<br>Drug: Atezolizumab<br>* Atezolizumab will be administered as per the schedules specified in the respective arms.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ia: Number of Participants with Dose Limiting Toxicities (DLTs) |  | From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment) | 
| Phase Ib: Number of Participants with DLTs |  | From Day 1 to Day 21 of Cycle 1 (21 days from date of first dose of study treatment) | 
| Phase Ia: Number of Participants with Treatment Emergent Adverse Events |  | Up to approximately 5 years | 
| Phase Ib: Number of Participants with Treatment Emergent Adverse Events |  | Up to approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase Ia and Phase Ib: Maximum Serum Concentration (Cmax) of RO7502175 |  | From Cycle 1 (each cycle is 21 days) Day1 and at multiple timepoints up to each follow-up visits (up to approximately 5 years) | 
| Phase Ia and Phase Ib: Objective Response Rate (ORR) |  | From Cycle 1(each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 5 years) | 
| Phase Ia and Phase Ib: Duration of Response (DOR) |  | From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 5 years) | 
| Phase Ia and Phase Ib: Progression Free Survival (PFS) |  | From Cycle 1 (each cycle is 21 days) Day 1, until disease progression, death, or end of study (up to approximately 5 years) | 
| Phase Ia and Phase Ib: Percentage of Participants With Anti-Drug Antibody (ADA) to RO7502175 |  | From Cycle 1 (each cycle is 21 days) Day 1 and at multiple timepoints up to treatment discontinuation (up to approximately 5 years) |