A Study to Evaluate the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-Care Chemotherapy in Participants With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of RO7496353 when administered in combination with a checkpoint inhibitor (CPI) with or without standard-of-care (SOC) chemotherapy in participants with locally advanced or metastatic solid tumors such as non-small cell lung cancer (NSCLC), gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC). The study will be conducted in 2 stages: an initial safety run-in stage and an expansion stage.

Official Title
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A Phase Ib, Open-Label, Multicenter Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7496353 in Combination With a Checkpoint Inhibitor With or Without Standard-of-Care Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Metastatic Solid Tumor, Non-small Cell Lung Cancer, Gastric Cancer, Pancreatic Ductal Adenocarcinoma

Intervention / Treatment
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* Drug: RO7496353
* Drug: Atezolizumab
* Drug: Capecitabine
* Drug: S-1
* Drug: Nivolumab
* Drug: Oxaliplatin
* Drug: Nab-paclitaxel
* Drug: Gemcitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy at least 3 months Adequate hematologic and end organ function Histologically confirmed locally advanced, recurrent, or metastatic incurable solid tumor malignancy Measurable disease according to RECIST v1.1 on computed tomography (CT) or magnetic resonance imaging (MRI) images within 28 days prior to enrollment Availability of representative tumor specimens in formalin-fixed, paraffin-embedded (FFPE) blocks or at least 15 unstained slides Exclusion Criteria: Pregnant or breastfeeding, or intending to become pregnant during the study or within 9 months after the final dose of oxaliplatin and within 6 months after the final dose of all other study treatment Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, and/or radiotherapy, within 3 weeks prior to initiation of study treatment Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina History of leptomeningeal disease Uncontrolled tumor-related pain Positive test for human immunodeficiency virus (HIV) infection Positive hepatitis B surface antigen (HbsAg) test, and/or positive total hepatitis B core antibody (HbcAb) test at screening Positive hepatitis C virus (HCV) antibody test at screening Known allergy or hypersensitivity to any component of the RO7496353 formulation or any of the study drugs or their excipients 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: Cohort A: NSCLC<br>Participants with NSCLC will receive RO7496353, and atezolizumab, given as an intravenous (IV) infusion at an assigned dose on Day 1 of each 21-day cycle until unacceptable toxicity or symptomatic deterioration attributed to disease progression. | Drug: RO7496353<br>* RO7496353 will be administered as per the schedules specified in the respective arms.<br>* Other names: SOF 10;Drug: Atezolizumab<br>* Atezolizumab will be administered as per the schedules specified in the respective arms.<br>* Other names: RO554126 7; Tecentriq;|
| Experimental: Cohort B: GC<br>Participants with GC will receive RO7496353, nivolumab, and oxaliplatin, given as an IV infusion at an assigned dose on Day 1 of each 21-day cycle along with either capecitabine or S-1, orally, twice daily on Days 1 to 14 of each cycle until unacceptable toxicity or symptomatic deterioration attributed to disease progression. | Drug: RO7496353<br>* RO7496353 will be administered as per the schedules specified in the respective arms.<br>* Other names: SOF 10;Drug: Capecitabine<br>* Capecitabine will be administered as per the schedules specified in the respective arms<br>Drug: S-1<br>* S-1 will be administered as per the schedules specified in the respective arms.<br>* Other names: Tegafur/Gimeracil/Oteracil potassium;Drug: Nivolumab<br>* Nivolumab will be administered as per the schedules specified in the respective arms.<br>Drug: Oxaliplatin<br>* Oxaliplatin will be administered as per the schedules specified in the respective arms.<br>|
| Experimental: Cohort C: PDAC<br>Participants with PDAC will receive RO7496353, and atezolizumab, given as an IV infusion at an assigned dose on Days 1 and 15 of each 28-day cycle along with nab-paclitaxel, and gemcitabine, also given as an IV infusion on Days 1, 8, 15 of each 28-day cycle until unacceptable toxicity or symptomatic deterioration attributed to disease progression. | Drug: RO7496353<br>* RO7496353 will be administered as per the schedules specified in the respective arms.<br>* Other names: SOF 10;Drug: Atezolizumab<br>* Atezolizumab will be administered as per the schedules specified in the respective arms.<br>* Other names: RO554126 7; Tecentriq;Drug: Nab-paclitaxel<br>* Nab-paclitaxel will be administered as per the schedules specified in the respective arms.<br>Drug: Gemcitabine<br>* Gemcitabine 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 |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) | AEs will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). | Up to approximately 29 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of RO7496353 |  | Up to approximately 29 months | 
| Cohort A and C: Serum Concentration of Atezolizumab |  | Up to approximately 29 months | 
| Percentage of Participants with Anti-Drug Antibody (ADA) to RO7496353 |  | Up to approximately 29 months | 
| Cohort A and C: Percentage of Participants with ADA to Atezolizumab |  | Up to approximately 29 months | 
| Confirmed Objective Response Rate (ORR) as Determined by the Investigator per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) |  | Up to approximately 29 months | 
| Duration of Response (DOR) as Determined by the Investigator per RECIST v1.1 |  | Up to approximately 29 months | 
| Progression Free Survival (PFS) as Determined by the Investigator per RECIST v1.1 |  | Up to approximately 29 months |