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

Genentech

Status and phase: Active, not recruiting; Phase 1

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

Treatments: Drug: Oxaliplatin; Drug: Atezolizumab; Drug: Nivolumab; Drug: S-1; Drug: Capecitabine; Drug: RO7496353; Drug: Gemcitabine; Drug: Nab-paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT05867121

GO44010

2022-502615-11-00 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 102 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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102 participants in 4 patient groups

Cohort A: NSCLC

Experimental group

Description:

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).

Treatment:

Drug: RO7496353

Drug: Atezolizumab

Cohort B: GC

Experimental group

Description:

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.

Treatment:

Drug: RO7496353

Drug: S-1

Drug: Capecitabine

Drug: Nivolumab

Drug: Oxaliplatin

Cohort C: PDAC

Experimental group

Description:

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.

Treatment:

Drug: Nab-paclitaxel

Drug: Gemcitabine

Drug: RO7496353

Drug: Atezolizumab

Substudy: UC

Experimental group

Description:

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.

Treatment:

Drug: RO7496353

Drug: Atezolizumab