Phase I Clinical Study on the Safety, Tolerance, Pharmacokinetics and Efficacy of Pan-KRAS Inhibitor YL-17231 in Patients With Advanced Solid Tumors With KRAS Mutation

Shanghai YingLi Pharmaceutical Co. Ltd.1 site in 1 country80 target enrollmentSeptember 28, 2023

ConditionsAdvanced Solid Tumor

InterventionsYL-17231

DrugsYL-17231

Overview

Phase: Phase 1
Intervention: YL-17231
Conditions: Advanced Solid Tumor
Sponsor: Shanghai YingLi Pharmaceutical Co. Ltd.
Enrollment: 80
Locations: 1
Primary Endpoint: DLTs
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a phase 1 open label multicenter study to evaluate the maximum tolerance, safety, tolerance and PK of oral YL-17231 in patients with advanced solid tumors with KRAS mutation, so as to confirm the recommended phase 2 dose of YL-17231 and obtain the preliminary efficacy information of patients with advanced solid tumors with KRAS mutation.

Detailed Description

The study will be conducted in China to provide safety, efficacy and PK data. A dose escalation part 1 will be conducted to determine the MTD, DLTs, and part 2 will confirm the safety/tolerability of the recommended Phase 2 dose (RP2D), of YL-17231 given twice daily, in patients with advanced solid tumors to obtain preliminary efficacy information. PK samplings at single dose stage Day 1 and at steady-state conditions (Cycle 1, Day 14) will be performed.

Registry

clinicaltrials.gov

Start Date

September 28, 2023

End Date

December 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Shanghai YingLi Pharmaceutical Co. Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•The patients must meet all the following inclusion criteria to be eligible for enrollment in this trial:
•Age between 18 and 75 years (inclusive), with no gender restriction.
•Locally advanced or metastatic solid tumors diagnosed histologically and genomically confirmed with KRAS mutation, excluding patients with a clear KRAS wild-type test report in the case of pancreatic cancer.
•A. For patients with NSCLC, previous treatment failure based on platinum-based first-line therapy; B. For patients with colorectal cancer, previous experience with at least two lines of systemic therapy (patients with colorectal cancer and high microsatellite instability should have received PD-1 or PD-L1 therapy if clinically applicable); C. For patients with solid tumors other than NSCLC or colorectal cancer, at least one prior systemic treatment is required.
•In the dose escalation phase, measurable or non-measurable tumor lesions are acceptable based on RECIST1.1 criteria; in the dose expansion phase, at least one measurable tumor lesion is required.
•ECOG performance status (PS) of 0-
•Estimated life expectancy of ≥3 months.
•Good organ function levels:
•Absolute neutrophil count (ANC) ≥1.5×109/L;
•Platelet count (PLT) ≥100×109/L;

Exclusion Criteria

•Patients with any of the following conditions are not eligible for enrollment in this study:
•Uncontrollable third-space effusion (such as large amounts of pleural or ascitic fluid).
•Grade 3 or 4 gastrointestinal bleeding or variceal bleeding requiring transfusion, endoscopy, or surgical intervention within the past 3 months.
•Previous diagnosis of other malignancies within the past five years, except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cured in situ cervical cancer.
•Inability to swallow, chronic diarrhea, or intestinal obstruction that could affect medication intake and absorption.
•History of significant neurological or psychiatric disorders.
•Active hepatitis B (positive for hepatitis B surface antigen and/or hepatitis B core antibody with HBV-DNA ≥103 copies/mL or ≥200 IU/mL) or hepatitis C (positive for hepatitis C virus antibody and/or HCV-RNA).
•History of immunodeficiency, including positive HIV test, acquired or congenital immunodeficiency disorders, organ transplantation, or allogeneic bone marrow transplantation.
•Major surgical procedures (excluding biopsy) within the past 4 weeks prior to the first administration of the study drug, significant trauma, or the need for elective surgery during the study period, or radical radiotherapy within the past 4 weeks prior to the first administration of the study drug.
•Moderate or severe cardiac diseases:

Arms & Interventions

YL-17231

YL-17231 will be administrated orally from 0.25mg QD, 0.5mg BID to 10mg BID in sequence during dose excalation part and selected doses in dose expansion part,for 21 consecutive days as a treatment cycle

Intervention: YL-17231

Outcomes

Primary Outcomes

DLTs

Time Frame: At the end of Cycle 1 (each cycle is 21 days)

Dose limited toxicities

TEAEs

Time Frame: From day 1 after taking the investigational product till 30 days after withdrawal from the study

Treatment emergent adverse events

Secondary Outcomes

Cmax(From day 1 to the end of Cycle 2 (each cycle is 21 days))
AUC(From day 1 to the end of Cycle 2 (each cycle is 21 days))
Disease control rate, DCR(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
Tmax(From day 1 to the end of Cycle 2 (each cycle is 21 days))
T1/2(From day 1 to the end of Cycle 2 (each cycle is 21 days))
The overall response rate (ORR)(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
DOR(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
Progression free survival, PFS(From date of screening until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months)
Overall survival, OS(From date of screening until the date of death from any cause, assessed up to 36 months)