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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Gastric Cancer; Non-small Cell Lung Cancer; Pancreatic Ductal Adenocarcinoma
• Intervention / Treatment: Drug: Atezolizumab; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: RO7496353; Drug: Capecitabine; Drug: S-1; Drug: Nivolumab; Drug: Nab-paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
  • São Paulo
    • Barretos, São Paulo, Brazil, 14784-400
      • Hospital de Cancer de Barretos
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A Gemelli
  • Lombardy
    • Milan, Lombardy, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda
  • Veneto
    • Verona, Veneto, Italy, 37134
      • Centro Ricerche Cliniche di Verona
• Japan
  • Chiba, Japan, 277-8577
    • National Cancer Center Hospital East
  • Kanagawa, Japan, 241-8515
    • Kanagawa cancer center
  • Shizuoka, Japan, 411-8777
    • Shizuoka Cancer Center
  • Tokyo, Japan, 104-0045
    • National Cancer Center Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer institute Hospital of Japanese Foundation for Cancer Research
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center - PPDS
  • Seoul, South Korea, 120-752
    • Severance Hospital Yonsei University Health System - Clinical Trials Center Pharmacy
• Spain
  • Madrid, Spain, 28027
    • Clinica Universidad de Navarra-Madrid
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • NEXT Oncology-Hospital Quironsalud Madrid
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Clinica Universitaria De Navarra
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06800
    • Ankara City Hospital
  • Lzmir, Turkey (Türkiye), 35340
    • Dokuz Eylul Universitesi Tip Fakultesi
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA University of California Los Angeles
  • Connecticut
    • New Haven, Connecticut, United States, 06510-3206
      • Yale School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: NSCLC; 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).	Drug: Atezolizumab; Atezolizumab will be administered as per the schedules specified in the respective arms.; Other Names: RO5541267; Tecentriq; Drug: RO7496353; RO7496353 will be administered as per the schedules specified in the respective arms.; Other Names: SOF 10
Experimental: Cohort B: GC; 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.	Drug: Oxaliplatin; Oxaliplatin will be administered as per the schedule specified in the respective arm.; Drug: RO7496353; RO7496353 will be administered as per the schedules specified in the respective arms.; Other Names: SOF 10; Drug: Capecitabine; Capecitabine will be administered as per the schedule specified in the respective arm.; Drug: S-1; S-1 will be administered as per the schedule specified in the respective arm.; Other Names: Tegafur/Gimeracil/Oteracil potassium; Drug: Nivolumab; Nivolumab will be administered as per the schedule specified in the respective arm.
Experimental: Cohort C: PDAC; 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.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedules specified in the respective arms.; Other Names: RO5541267; Tecentriq; Drug: Gemcitabine; Gemcitabine will be administered as per the schedule specified in the respective arm.; Drug: RO7496353; RO7496353 will be administered as per the schedules specified in the respective arms.; Other Names: SOF 10; Drug: Nab-paclitaxel; Nab-paclitaxel will be administered as per the schedule specified in the respective arm.
Experimental: Substudy: UC; 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.	Drug: Atezolizumab; Atezolizumab will be administered as per the schedules specified in the respective arms.; Other Names: RO5541267; Tecentriq; Drug: RO7496353; RO7496353 will be administered as per the schedules specified in the respective arms.; Other Names: SOF 10

What is the study measuring?

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 33 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Other Outcome Measures

Outcome Measure	Time Frame
Cohort A and C: Serum Concentration of Atezolizumab	Up to approximately 33 months
Cohort A and C: Percentage of Participants With ADAs to Atezolizumab	Up to approximately 33 months

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): October 2, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: May 10, 2023
• First Submitted That Met QC Criteria: May 10, 2023
• First Posted (Actual): May 19, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Urothelial Carcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Stomach Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Transitional Cell; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Fluorouracil; Capecitabine; Oxaliplatin; Nivolumab; Gemcitabine; Tegafur; atezolizumab; 130-nm albumin-bound paclitaxel; S 1 (combination)
• Other Study ID Numbers: GO44010; 2022-502615-11-00 (Ctis: EU Clinical Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No