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)

Phase 1

Recruiting

• Conditions: Neoplasms
• Interventions: Drug: RO7673396

• Registration Number: NCT06884618
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-18
• Study First Submitted QC: 2025-03-18
• Study First Posted: 2025-03-19
• Study Start: 2025-04-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-13
• Primary Completion: 2028-08-31
• Study Completion: 2029-05-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 345

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
• 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
• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Stage I	RO7673396	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 and/or loss of clinical benefit as determined by the investigator.
Stage II	RO7673396	Participants with advanced solid tumors harboring RAS mutations will receive RO7673396 at the dose determined in Stage 1, until unacceptable toxicity or disease progression and/or loss of clinical benefit as determined by the investigator.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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

Trial Locations

Locations (2)

New Zealand Clinical Research - Auckland; 🇳🇿 Auckland, New Zealand

New Zealand Clinical Research - Christchurch; 🇳🇿 Christchurch, New Zealand