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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

Phase 1
Active, not recruiting
Conditions
Metastatic Solid Tumor
Non-small Cell Lung Cancer
Gastric Cancer
Pancreatic Ductal Adenocarcinoma
Interventions
Registration Number
NCT05867121
Lead Sponsor
Genentech, Inc.
Brief Summary

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.

Detailed Description

Not available

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 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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Cohort B: GCCapecitabineParticipants 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.
Cohort C: PDACGemcitabineParticipants 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.
Cohort C: PDACRO7496353Participants 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.
Cohort C: PDACAtezolizumabParticipants 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.
Cohort C: PDACNab-paclitaxelParticipants 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.
Cohort A: NSCLCRO7496353Participants 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.
Cohort B: GCRO7496353Participants 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.
Cohort B: GCS-1Participants 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.
Cohort A: NSCLCAtezolizumabParticipants 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.
Cohort B: GCNivolumabParticipants 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.
Cohort B: GCOxaliplatinParticipants 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.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants with Adverse Events (AEs)Up to approximately 29 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
NameTimeMethod
Percentage of Participants with Anti-Drug Antibody (ADA) to RO7496353Up 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 v1.1Up to approximately 29 months
Progression Free Survival (PFS) as Determined by the Investigator per RECIST v1.1Up to approximately 29 months
Plasma Concentration of RO7496353Up to approximately 29 months

Trial Locations

Locations (30)

Ege University Medical Faculty

🇹🇷

Izmir, Turkey

Dokuz Eylul Universitesi Tip Fakultesi

🇹🇷

Lzmir, Turkey

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

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

🇮🇹

Milano, Lombardia, Italy

Centro Ricerche Cliniche Di Verona

🇮🇹

Verona, Veneto, Italy

National Cancer Center Hospital East

🇯🇵

Chiba, Japan

Kanagawa Cancer Center

🇯🇵

Kanagawa, Japan

Shizuoka Cancer Center

🇯🇵

Shizuoka, Japan

National Cancer Center Hospital

🇯🇵

Tokyo, Japan

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

🇯🇵

Tokyo, Japan

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

Asan Medical Center

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center - PPDS

🇰🇷

Seoul, Korea, Republic of

Severance Hospital Yonsei University Health System - Clinical Trials Center Pharmacy

🇰🇷

Seoul, Korea, Republic of

Auckland City Hospital

🇳🇿

Auckland, New Zealand

University Clinical Center of Serbia -PPDS

🇷🇸

Belgrade, Serbia

Clinical Hospital Center Bezanijska Kosa

🇷🇸

Belgrade, Serbia

University Clinical Center Kragujevac

🇷🇸

Kragujevac, Serbia

NEXT Oncology-Hospital Quironsalud Madrid

🇪🇸

Pozuelo de Alarcon, Madrid, Spain

Clinica Universitaria de Navarra

🇪🇸

Pamplona, Navarra, Spain

Clinica Universidad de Navarra-Madrid

🇪🇸

Madrid, Spain

Hospital Clinico Universitario de Valencia

🇪🇸

Valencia, Spain

Ankara City Hospital

🇹🇷

Ankara, Turkey

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