A Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Preliminary Clinical Activity of RO7673396 in Participants With Advanced Solid Tumors Harboring Rat Sarcoma Viral Oncogene Homolog (RAS) Mutation(s)

A Phase I Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Clinical Activity of RO7673396 as a Single Agent and in Combination With Other Anticancer Therapies in Patients With Advanced Solid Tumors Harboring RAS Mutation(s)

This study aims to evaluate the safety and tolerability of RO7673396 in participants with advanced solid tumors harboring RAS mutation(s). This study consists of two stages: Stage 1 (Dose Escalation) and Stage 2 (Dose Expansion). Stage 1 will define the recommended dose(s) for expansion (RDEs) of RO7673396. Stage 2 will evaluate preliminary anti-tumor activity of the RDE(s) defined in Stage 1 and of other doses of interest for future development in selected solid tumor indications.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms
• Intervention / Treatment: Drug: RO7673396

• Study Type: Interventional
• Enrollment (Estimated): 405
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: YO45758 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S.); Email: global-roche-genentech-trials@gene.com

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • St Vincent's Hospital Sydney
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Recruiting
      • Peter MacCallum Cancer Center
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Hospital
• China
  • Guangzhou, China, 510050
    • Recruiting
    • Sun Yat-Sen University Cancer Center;Department of Thoracic Surgery
  • Shanghai, China, 201315
    • Recruiting
    • Fudan University Shanghai Cancer Center
  • Wuhan, China, 430079
    • Recruiting
    • Hubei Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510555
      • Recruiting
      • Sun Yat-Sen University Cancer Center - Huangpu Campus
• Denmark
  • København Ø, Denmark, 2100
    • Recruiting
    • Rigshospitalet
• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Prince of Wales Hospital
• New Zealand
  • Auckland, New Zealand, 1010
    • Recruiting
    • New Zealand Clinical Research - Auckland
  • Christchurch, New Zealand, 8011
    • Recruiting
    • New Zealand Clinical Research - Christchurch
• Singapore
  • Singapore, Singapore, 168583
    • Recruiting
    • National Cancer Centre - 30 Hospital Blvd
• Spain
  • Navarre
    • Pamplona, Navarre, Spain, 31008
      • Recruiting
      • Clinica Universidad de Navarra
• Taiwan
  • Tainan, Taiwan, 70403
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado - Anschutz Medical Campus - PPDS
  • Connecticut
    • New Haven, Connecticut, United States, 06519-1110
      • Recruiting
      • Smilow Cancer Hospital at Yale New Haven
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists - Sarasota (North Catttlemen Rd)
  • Texas
    • Houston, Texas, United States, 77030-3721
      • Recruiting
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229-4427
      • Recruiting
      • South Texas Accelerated Research Therapeutics (START)

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically documented, locally advanced, recurrent, or metastatic incurable solid tumors
• Participants with measurable disease according to RECIST v1.1 assessed by the investigator
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy ≥12 weeks
• Adequate hematologic and end-organ function
• Confirmed presence of the RAS mutation(s)

Exclusion Criteria:

• Current participant or enrollment in another interventional clinical trial
• Known hypersensitivity or medical contraindication to any component of RO7673396 formulation
• Refractory nausea and vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate study treatment absorption
• Known and untreated, or active central nervous system (CNS) metastases
• Participants with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal (GI) surgery including gastric resection, a history of inflammatory bowel disease (IBD)
• Treatment with chemotherapy, immunotherapy, biologic therapy, or an investigational agent as anti-cancer therapy within 4 weeks or five half-lives prior to initiation of study treatment
• Participants who are on acid-reducing agents and unable to safely discontinue them as required in the study
• Major surgical procedure within 28 days prior to initiation of study treatment, or incomplete recovery from surgery that would interfere with the determination of safety or efficacy of study treatment, or anticipation of need for a major surgical procedure during the study
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Known clinically significant liver disease

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage I; Participants with advanced solid tumors harboring RAS mutations will receive multiple ascending doses of RO7673396, as per a pre-defined dosing regimen until unacceptable toxicity or disease progression (PD) and/or loss of clinical benefit as determined by the investigator.	Drug: RO7673396; RO7673396 will be administered as per the schedule specified in the protocol.
Experimental: Stage II; Participants with advanced solid tumors harboring RAS mutations will receive RO7673396 at the dose determined in Stage 1, until unacceptable toxicity or PD and/or loss of clinical benefit as determined by the investigator.	Drug: RO7673396; RO7673396 will be administered as per the schedule specified in the protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Stage I: Number of Participants With Adverse Events (AEs)	Up to approximately 40 months
Stage I: Number of Participants With Dose-limiting Toxicities (DLTs)	Up to Day 21
Stage II: Objective Response Rate (ORR) as Assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)	Up to approximately 40 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentrations of RO7673396 and its Metabolite(s)	Up to approximately 49 months
Stage I: ORR as Assessed by the Investigator per RECIST V1.1	Up to approximately 49 months
Stage I and II: Duration of Response (DOR) as Assessed by the Investigator per RECIST V1.1	Up to approximately 49 months
Stage I and II: Progression-free Survival (PFS) as Assessed by the Investigator per RECIST V1.1	Up to approximately 49 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2025
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): May 25, 2029

Study Registration Dates

• First Submitted: March 18, 2025
• First Submitted That Met QC Criteria: March 18, 2025
• First Posted (Actual): March 19, 2025

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 16, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: RAS Mutated Solid Tumors
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: YO45758; 2024-519622-20-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

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