Clinical trial NCT06884618: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Keywords: RAS Mutated Solid Tumors
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2025-03-19
Enrollment: 345
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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
* 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

Primary outcomes:
measure: Stage I: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 40 months
measure: Stage I: Number of Participants With Dose-limiting Toxicities (DLTs)
timeFrame: Up to Day 21
measure: Stage II: Objective Response Rate (ORR) as Assessed by the Investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST V1.1)
timeFrame: Up to approximately 40 months
Secondary outcomes:
measure: Plasma Concentrations of RO7673396 and its Metabolite(s)
timeFrame: Up to approximately 49 months
measure: Stage I: ORR as Assessed by the Investigator per RECIST V1.1
timeFrame: Up to approximately 49 months
measure: Stage I and II: Duration of Response (DOR) as Assessed by the Investigator per RECIST V1.1
timeFrame: Up to approximately 49 months
measure: Stage I and II: Progression-free Survival (PFS) as Assessed by the Investigator per RECIST V1.1
timeFrame: Up to approximately 49 months
Other outcomes:
Locations:
city: Parkville
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Auckland
country: New Zealand
facility: New Zealand Clinical Research - Auckland
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research - Christchurch
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: