A Study to Evaluate Safety, Pharmacokinetics, & 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; Urothelial Carcinoma Substudy in Association With RO7496353 Study GO44010

Phase 1

Active, not recruiting

• Conditions: Non-small Cell Lung Cancer; Gastric Cancer; Pancreatic Ductal Adenocarcinoma
• Interventions: Drug: RO7496353; Drug: Atezolizumab; Drug: Capecitabine; Drug: S-1; Drug: Nab-paclitaxel; Drug: Nivolumab; Drug: Gemcitabine; Drug: Oxaliplatin

• Registration Number: NCT05867121
• Lead Sponsor: Genentech, Inc.

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of RO7496353 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 substudy will evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary anti-tumor activity of RO7496353 in combination with atezolizumab in patients with locally advanced or metastatic urothelial carcinoma (UC).

The parent and substudy will be conducted in 2 stages: an initial safety run-in stage and an expansion stage.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-05-10
• Study First Submitted QC: 2023-05-10
• Study First Posted: 2023-05-19
• Study Start: 2023-10-02
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-04
• Last Update Posted: 2025-07-09
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 102

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of 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

• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort A: NSCLC	RO7496353	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 (PD).
Cohort A: NSCLC	Atezolizumab	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 (PD).
Cohort B: GC	RO7496353	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 PD.
Cohort B: GC	Capecitabine	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 PD.
Cohort B: GC	S-1	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 PD.
Cohort B: GC	Nivolumab	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 PD.
Cohort B: GC	Oxaliplatin	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 PD.
Cohort C: PDAC	RO7496353	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 PD.
Cohort C: PDAC	Atezolizumab	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 PD.
Cohort C: PDAC	Nab-paclitaxel	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 PD.
Cohort C: PDAC	Gemcitabine	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 PD.
Substudy: UC	RO7496353	Participants with UC will receive RO7496353, and atezolizumab, given as an IV infusion at an assigned dose on Day 1 of each 21-day cycle until unacceptable toxicity or symptomatic deterioration attributed to PD.
Substudy: UC	Atezolizumab	Participants with UC will receive RO7496353, and atezolizumab, given as an IV infusion at an assigned dose on Day 1 of each 21-day cycle until unacceptable toxicity or symptomatic deterioration attributed to PD.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events (AEs)	Up to approximately 33 months	AEs will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).

Secondary Outcome Measures

Name	Time	Method
Plasma Concentration of RO7496353	Up to approximately 33 months
Percentage of Participants With Anti-drug Antibody (ADA) to RO7496353	Up to approximately 33 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 33 months
Duration of Response (DOR) as Determined by the Investigator per RECIST v1.1	Up to approximately 33 months
Progression-free Survival (PFS) as Determined by the Investigator per RECIST v1.1	Up to approximately 33 months

Trial Locations

Locations (29)

Hospital de Clinicas de Porto Alegre (HCPA) - PPDS; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

The Catholic University of Korea, Seoul St. Mary's Hospital; 🇰🇷 Seoul, Korea, Republic of

UCLA University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

Yale School of Medicine; 🇺🇸 New Haven, Connecticut, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

St Vincent'S Hospital; 🇦🇺 Darlinghurst, New South Wales, Australia

Flinders Medical Centre; 🇦🇺 Bedford Park, South Australia, Australia

Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS); 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Hospital de Câncer de Barretos; 🇧🇷 Barretos, São Paulo, Brazil

Fondazione Policlinico Universitario A Gemelli; 🇮🇹 Roma, Lazio, Italy

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