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

NCT06078800 | Unknown Phase 1

• 1 other identifier: YL-17231-002
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced Solid Tumor

Keywords

Nonsmall-cell lung cancer（NSCLC）; Colorectal cancer（CRC）; Pancreatic carcinoma; KRAS mutation

Outcome Measures

Primary Outcomes (2)

• DLTs

  Dose limited toxicities

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

• TEAEs

  Treatment emergent adverse events

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

Secondary Outcomes (9)

• 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)

• 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

Study Arms (1)

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

Drug: YL-17231

Interventions

YL-17231 DRUG

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.

Also known as: Pan-KRAS Inhibitor YL-17231

YL-17231

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 0-1.
• Estimated life expectancy of ≥3 months.
• 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.

You may not qualify if:

• 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:
• Myocardial infarction, angina, III/IV congestive heart failure, pericardial effusion, or uncontrolled severe hypertension (up to 150/90 mmHg or below) within the past 6 months prior to the first administration of the study drug;
• Clinically significant electrocardiogram abnormalities, such as symptomatic or persistent atrial or ventricular arrhythmias, second or third-degree atrioventricular block, bundle branch block, or ventricular hypertrophy;
• Significant abnormalities on echocardiography, such as moderate or severe valvular dysfunction, assessed based on institutional lower limits; patients with minimal or mild valve regurgitation (tricuspid, pulmonary, mitral, or aortic) can be included in this study;
• Various factors that may increase the risk of QTcF prolongation or cardiac arrhythmia events, such as hypokalemia, congenital long QT syndrome, or concomitant use of drugs that may prolong the QT interval.
• Untreated brain metastases that meet one or more of the following criteria:

Sponsors & Collaborators

• Shanghai YingLi Pharmaceutical Co. Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

RECRUITING

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• Xu Ruihua, PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xu Ruihua, PhD

CONTACT

13922206676; xurh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2023
• First Posted: October 12, 2023
• Study Start: September 28, 2023
• Primary Completion: March 1, 2025
• Study Completion: December 1, 2025
• Last Updated: October 12, 2023

Record last verified: 2023-10

Locations

CN (1)