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

NCT05867121 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: GO440102022-502615-11-00
• Study Type: interventional
• Target: 102
• Locations: 9 countries
• Sites: 27

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.

Conditions

Non-small Cell Lung Cancer; Gastric Cancer; Pancreatic Ductal Adenocarcinoma

Keywords

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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 Outcomes (2)

• 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

Study Arms (4)

Cohort A: NSCLC

EXPERIMENTAL

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: RO7496353; Drug: Atezolizumab

Cohort B: GC

EXPERIMENTAL

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: RO7496353; Drug: Capecitabine; Drug: S-1; Drug: Nivolumab; Drug: Oxaliplatin

Cohort C: PDAC

EXPERIMENTAL

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: RO7496353; Drug: Atezolizumab; Drug: Nab-paclitaxel; Drug: Gemcitabine

Substudy: UC

EXPERIMENTAL

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: RO7496353; Drug: Atezolizumab

Interventions

RO7496353 DRUG

RO7496353 will be administered as per the schedules specified in the respective arms.

Also known as: SOF 10

Cohort A: NSCLC; Cohort B: GC; Cohort C: PDAC; Substudy: UC

Atezolizumab DRUG

Atezolizumab will be administered as per the schedules specified in the respective arms.

Also known as: RO5541267; Tecentriq

Cohort A: NSCLC; Cohort C: PDAC; Substudy: UC

Capecitabine DRUG

Capecitabine will be administered as per the schedule specified in the respective arm.

Cohort B: GC

S-1 DRUG

S-1 will be administered as per the schedule specified in the respective arm.

Also known as: Tegafur/Gimeracil/Oteracil potassium

Cohort B: GC

Nivolumab DRUG

Nivolumab will be administered as per the schedule specified in the respective arm.

Cohort B: GC

Oxaliplatin DRUG

Oxaliplatin will be administered as per the schedule specified in the respective arm.

Cohort B: GC

Nab-paclitaxel DRUG

Nab-paclitaxel will be administered as per the schedule specified in the respective arm.

Cohort C: PDAC

Gemcitabine DRUG

Gemcitabine will be administered as per the schedule specified in the respective arm.

Cohort C: PDAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead
• Chugai Pharmaceutical: collaborator

Study Sites (27)

UCLA University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510-3206, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

St Vincent'S Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Hospital de Câncer de Barretos

Barretos, São Paulo, 14784-400, Brazil

Location

Fondazione Policlinico Universitario A Gemelli

Rome, Lazio, 00168, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - Presidio Ospedaliero Ospedale Niguarda Ca' Granda

Milan, Lombardy, 20162, Italy

Location

Centro Ricerche Cliniche Di Verona

Verona, Veneto, 37134, Italy

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Kanagawa Cancer Center

Kanagawa, 241-8515, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Tokyo, 135-8550, Japan

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center - PPDS

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

Severance Hospital Yonsei University Health System - Clinical Trials Center Pharmacy

Seoul, 120-752, South Korea

Location

NEXT Oncology-Hospital Quironsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Clinica Universitaria de Navarra

Pamplona, Navarre, 31008, Spain

Location

Clinica Universidad de Navarra-Madrid

Madrid, 28027, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Ankara City Hospital

Ankara, 06800, Turkey (Türkiye)

Location

Dokuz Eylul Universitesi Tip Fakultesi

Lzmir, 35340, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Stomach Neoplasms; Carcinoma, Transitional Cell

Interventions

atezolizumab; Capecitabine; S 1 (combination); Tegafur; Nivolumab; Oxaliplatin; 130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2023
• First Posted: May 19, 2023
• Study Start: October 2, 2023
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2); KR (5); BR (2); ES (4); JP (5); US (3); AU (2); IT (3); NZ (1)