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)

Roche

Status and phase: Enrolling; Phase 1

Conditions: Neoplasms

Treatments: Drug: RO7673396

Study type: Interventional

Funder types: Industry

Identifiers

NCT06884618

2024-519622-20-00 (Registry Identifier)

YO45758

Details and patient eligibility

About

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.

Enrollment: 345 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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345 participants in 2 patient groups

Stage I

Experimental group

Description:

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.

Treatment:

Drug: RO7673396

Stage II

Experimental group

Description:

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.

Treatment:

Drug: RO7673396