A Study of YL-17231 in Patients With Advanced Solid Tumors

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: YL-17231. After a screening period of approximately 14 days, eligible patients will receive oral YL-17231 once or twice daily until documented disease progression, unacceptable AEs, intercurrent illness preventing further administrations of study treatment, investigator's decision to withdrawal, the patient's consent of withdrawal, pregnancy, or for administrative reasons. Following the end of treatment, patients will continue to be followed for safety for 30 days. Patients who permanently discontinue study treatment for reasons other than disease progression will have post-treatment follow-up for disease assessment until start of new anticancer treatment, patient's consent of withdrawal, lost to follow-up, death, or until the Sponsor stops the study, whichever comes first.

Arm public domain (ClinicalTrials.gov)

YL-17231 (experimental): 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

Primary outcome public domain (ClinicalTrials.gov)

DLTs. Dose limited toxicities Time frame: At the end of Cycle 1 (each cycle is 21 days).

Primary outcome public domain (ClinicalTrials.gov)

TEAEs. Treatment emergent adverse events Time frame: From day 1 after taking the investigational product till 30 days after withdrawal from the study.

Secondary outcome public domain (ClinicalTrials.gov)

Cmax. Time frame: From day 1 to the end of Cycle 2 (each cycle is 21 days).

Secondary outcome public domain (ClinicalTrials.gov)

AUC. Time frame: From day 1 to the end of Cycle 2 (each cycle is 21 days).

Secondary outcome public domain (ClinicalTrials.gov)

Tmax. Time frame: From day 1 to the end of Cycle 2 (each cycle is 21 days).

Secondary outcome public domain (ClinicalTrials.gov)

T1/2. Time frame: From day 1 to the end of Cycle 2 (each cycle is 21 days).

Secondary outcome public domain (ClinicalTrials.gov)

The overall response rate (ORR). Time frame: 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.

Secondary outcome public domain (ClinicalTrials.gov)

DOR. Time frame: 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.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: The patients must meet all the following inclusion criteria to be eligible for enrollment in this trial: 1. Age between 18 and 75 years (inclusive), with no gender restriction. 2. 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. 3. 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. 4. ECOG performance status (PS) of 0-1. 5. Estimated life expectancy of ≥3 months. 6. Good organ function levels: * Absolute neutrophil count (ANC) ≥1.5×109/L; * Platelet count (PLT) ≥100×109/L; * Hemoglobin (Hb) ≥90g/L (no blood transfusion within 14 days before screening); * Total bilirubin (TBIL) ≤1.5 times the upper limit of normal; * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal (≤5.0 times the upper limit of normal for patients with liver metastasis); * Serum creatinine (Cr) ≤1.5 times the upper limit of normal or creatinine clearance ≥50ml/min; * Left ventricular ejection fraction (LVEF) ≥50%; * Fridericia-corrected QT interval (QTcF) \<450ms. 7. Washout period of ≥4 weeks for macromolecular agents and intravenous chemotherapy drugs, and ≥2 weeks for oral fluoropyrimidine and small molecule targeted drugs. 8. Fertile males and females must agree to use medically approved contraceptive measures during the study period and for 6 months following the last administration of the study drug. 9. Women of childbearing potential must have a negative pregnancy test within 7 days prior to the first administration of the study drug; patients must not be breastfeeding, and if the subject has already ceased breastfeeding at the time of study entry, breastfeeding must have been discontinued from the day of the first administration of the study drug till …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 80 participants (estimated).