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)

Official title

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)

Overview

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.

Interventions

• Drug RO7673396
  RO7673396 will be administered as per the schedule specified in the protocol.

Primary outcome measures

• Stage I: Number of Participants With Adverse Events (AEs) [Time frame: Up to approximately 40 months]
• Stage I: Number of Participants With Dose-limiting Toxicities (DLTs) [Time frame: 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) [Time frame: Up to approximately 40 months]

Secondary outcome measures (4)

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

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 6 centers

• City of Hope Comprehensive Cancer Center — Duarte
• University of Colorado - Anschutz Medical Campus - PPDS — Aurora
• Smilow Cancer Hospital at Yale New Haven — New Haven
• Florida Cancer Specialists - Sarasota (North Catttlemen Rd) — Sarasota
• MD Anderson Cancer Center — Houston
• South Texas Accelerated Research Therapeutics (START) — San Antonio

China · 4 centers

• Sun Yat-Sen University Cancer Center - Huangpu Campus — Guangzhou
• Sun Yat-Sen University Cancer Center;Department of Thoracic Surgery — Guangzhou
• Fudan University Shanghai Cancer Center — Shanghai
• Hubei Cancer Hospital — Wuhan

Australia · 2 centers

• St Vincent's Hospital Sydney — Darlinghurst
• Peter MacCallum Cancer Center — Parkville

New Zealand · 2 centers

• New Zealand Clinical Research - Auckland — Auckland
• New Zealand Clinical Research - Christchurch — Christchurch

Taiwan · 2 centers

• National Cheng Kung University Hospital — Tainan
• National Taiwan University Hospital — Taipei

Canada · 1 center

• Princess Margaret Hospital — Toronto

Denmark · 1 center

• Rigshospitalet — København Ø

Hong Kong · 1 center

• Prince of Wales Hospital — Hong Kong

Singapore · 1 center

• National Cancer Centre - 30 Hospital Blvd — Singapore

Spain · 1 center

• Clinica Universidad de Navarra — Pamplona

Identifiers

NCT: NCT06884618 · YO45758 · 2024-519622-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗