NCT06096974

Pan-RAS Inhibitor YL-17231 in Patients With Advanced Solid Tumors Harboring Mutations in KRAS, HRAS, or NRAS

A Multi-Center, Open-Label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumor Activity of Pan-RAS Inhibitor YL-17231 in Patients With Advanced Solid Tumors Harboring Mutations in KRAS, HRAS, or NRAS

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Shanghai YingLi Pharmaceutical Co. Ltd. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the safety, tolerability, drug levels, pharmacodynamic effects, and clinical activity of YL 17231 in patients with advanced solid tumors harboring mutations in KRAS, HRAS, or NRAS.

Detailed description

The study is a Phase 1, multi-center, open label study in 2 parts. Part 1 (Phase Ia): This is a 3 + 3 design dose escalation study, to evaluate the safety and tolerability, and to determine the MTD and/or RP2D of YL-17231 treatment when administered orally QD in patients with advanced solid tumors harboring mutations in KRAS, HRAS or NRAS. Up to 9 doses cohorts are planned for the dose escalation part of the study, with the starting dose of 0.25mg QD. The actual number of dose cohorts to be explored in this study will be determined by the non-tolerable dose based on dose limiting toxicities (DLTs) in conjunction with the PK and preliminary efficacy signal data. If suggested by safety and PK findings from planned dose treatment cohorts, additional dose levels may be evaluated and dosing interval may be modified under the Safety Monitoring Committee (SMC) guidance. In Part 1, the 3+3 trial design for the dose escalation will be used and a total of 9 dose levels starting dose of 0.25 mg OD is planned. One cycle is 21 days. DLT observation period is one cycle. The maximum tolerated dose (MTD) is the highest dose at which ≤1 of 6 patients experiences a DLT during the DLT observation period. The study will identify a maximum tolerated dose (MTD) if possible, with safety and tolerability data. All available data, including safety, tolerability, PK, PD and preliminary anti-tumor activity from each cohort will be reviewed by the SMC to determine the RP2D. Patients may be permitted an intra-patient dose-escalation of YL-17231 to a higher dose level that has been cleared and deemed safe by the SMC if they have completed Cycle 2 at their initial enrolled dose level and continued on-study with no treatment related ≥ Grade 2 AEs. The Investigator must consult with the Medical Monitor to confirm if the patient is permitted be dose-escalated to a dose-level already cleared by the SMC. Backfilling Additional patients (up to total of 12) may be enrolled in the dose levels which have been cleared and deemed safe by SMC to further evaluate the safety, tolerability and PK. This is referred to as backfilling. Part 2 (Phase Ib): This is a dose expansion phase to further evaluate the safety, tolerability and preliminary anti-tumor activity of YL 17231 at the RP2D selected by SMC. The number of patients to be enrolled for the expansion cohorts, the RP2D and the desired patient population will be determined by the emerging data from part 1 of the study, including safety, tolerability, PK, PD and preliminary anti-tumor efficacy, as well as any other relevant evolving clinical data, and will be clarified through a protocol amendment.

Conditions

• Advanced Solid Tumors

Interventions

Type	Name	Description
DRUG	YL-17231	YL-17231 will be administered orally once daily in a continuous regimen

Timeline

• Start date: 2023-10-24
• Primary completion: 2025-10-01
• Completion: 2026-04-01
• First posted: 2023-10-24
• Last updated: 2025-04-09

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study