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

NCT06096974 | Recruiting Phase 1 FDA Drug

• 1 other identifier: YL-17231-001
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Advanced Solid Tumors

Keywords

KRAS, HRAS, or NRAS Mutations

Outcome Measures

Primary Outcomes (3)

• Occurrence of dose limiting toxicities (DLTs)

  A toxicity will be considered dose-limiting if it occurs during the first cycle (21 days) of treatment with YL-17231.

  The first cycle (21 days)

• TEAEs

  AEs will be coded using Medical Dictionary for Regulatory Activities current version. AEs will be regarded as treatment-emergent AEs (TEAEs) if they occur after first treatment. The frequencies will be presented including number and percentages of patients having experienced an event and the total number of events.

  Through study completion, an average of 1 year

• SAEs

  Serious AEs

  Through study completion, an average of 1 year

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  From first dose of study treatment to the first documented disease progression or death due to any cause, whichever occurs first， assessed up to 30 months.

• Duration of Response (DOR)

  From first documentation of a response (PR or CR) to the first documented disease progression or death due to any cause, whichever occurs first， assessed up to 30 months.

• Progression Free Survival (PFS)

  From first dose of study treatment to the first documented disease progression or death due to any cause, whichever occurs first, assessed up to 30 months.

• Disease Control Rate (DCR)

  From first dose of study treatment to the first documented disease progression or death due to any cause, whichever occurs first, assessed up to 30 months.

• AUC(0-T)

  During Cycles 1 and 2 (each cycle is 21 days)

Study Arms (1)

Dose Escalation and Expansion

EXPERIMENTAL

Dose escalation of YL-17231 to determine maximum tolerated dose.Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of YL-17231 to recommend Phase 2 regimens

Drug: YL-17231

Interventions

YL-17231 DRUG

YL-17231 will be administered orally once daily in a continuous regimen

Dose Escalation and Expansion

Eligibility Criteria

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

You may qualify if:

• Unresectable or metastatic advanced solid tumors with no standard therapies, or having progressed on or intolerable to standard therapies.
• Advanced solid tumors harboring mutations in KRAS, HRAS or NRAS as determined by laboratory testing, including local laboratory testing.
• Measurable disease with at least one lesion amenable to response assessment per RECIST 1.1.
• Demonstrate adequate organ function as defined below. All screening laboratories should be performed within 7 days of study treatment initiation.
• ）Absolute neutrophil count (ANC) ≥1.2 × 10\^9/L；2）Platelets ≥100 × 10\^9/L Hemoglobin ≥9 g/dL or ≥5.6 mmol/L；3）Measured or calculated creatinine clearance (CrCl)(Cockcroft-Gault) ≥60 mL/min；4）Total bilirubin ≤1.5 × ULN (patients with Gilbert's syndrome, total bilirubin ≤3.0 × ULN) ；5）Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 × ULN for patients with liver metastases
• Has an ECOG performance status of 0-1.
• Life expectancy ≥12 weeks at baseline.
• Women of childbearing potential must have negative serum or urine pregnancy test within 72 hours prior to receiving the first study drug administration. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• For women of childbearing potential, must be willing to use an adequate method of contraception from 30 days prior to the first study drug administration and at least 3 months following last day study drug administration.
• Male patients of childbearing potential must be surgically sterile, or must agree to use adequate method of contraception during the study and at least 3 months following the last day of study drug administration.
• Age ≥18 years at screening.
• Able and willing to provide written informed consent and to follow study instructions.
• Washout from prior anti-tumor therapy:1）Cytotoxic therapies ≥ 3 weeks Mitomycin C or nitrosoureas ≥ 6 weeks；2）Small molecule agents ≥2 weeks or 5x T1/2, whichever is longer；3）Biologic agents (e.g., antibodies) ≥ 4weeks Immunotherapy (e.g., CTLA4, PD-1, PD-L1 inhibitors) ≥ 4 weeks；4）Radiotherapy ≥ 4 weeks；5）Limited field radiotherapy or palliative radiotherapy ≥ 2 weeks ；6）Major surgery, excluding biopsy ≥ 4 weeks (exception: patients may enroll if fully recovered or without intolerable or clinically significant adverse effects, but at least 14 days must have elapsed between major surgery and first study drug administration)；7）Study drug with an investigational product, or non-approved use of a drug or device ≥ 4 weeks (≥2 weeks or 5x T1/2, whichever is longer for small molecule agents

You may not qualify if:

• Known symptomatic brain metastases requiring dexamethasone ≥4mg (or equivalent) or requiring steroid dose increase within 14 days prior to the first dose of YL-17231.
• Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment.
• Unresolved toxicities from prior therapy, defined as having not resolved to NCI CTCAE v.5.0 Grade ≤1 1 or baseline, with exception of endocrinopathies from prior therapy and successfully treated (such as hypothyroidism), alopecia, vitiligo, and ≤ grade 2 peripheral neuropathy.
• Human immunodeficiency virus (HIV) infection with a current or a known history of AIDS-defining illness or HIV infection with a CD4+ T cell count \<350 cells/µL and an HIV viral load more than 400 copies/µL.
• Patients with active viral (any etiology) hepatitis are excluded. However, patients with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen test and a positive anti-hepatitis core antigen antibody test) who have a viral load below the limit quantification (HBV DNA titer \<1000 cps/mL or 200 IU/mL), and are not currently on viral suppressive therapy may be eligible and should be discussed with the Medical Monitor. Patients with a history of hepatitis C virus (HCV) infection who have completed curative antiviral treatment and have a viral load below the limit of quantitation may be eligible and should be discussed with the Medical Monitor.
• Any of the following cardiac criteria experienced currently or within the last 6 months:
• Congestive heart failure (New York Heart Association ≥ Class 2).
• Any clinically significant abnormalities (as assessed by the Investigator) in rhythm, conduction, or morphology of resting electrocardiograms (ECGs), e.g., complete left bundle branch block or third-degree heart block.
• Acute coronary syndrome within 6 months.
• Clinically significant cardiac arrhythmia.
• Mean QTC interval corrected (Frederica) for heart rate \>450 ms.
• Left ventricular ejection fraction (LVEF) \<50% or the lower limit of normal (per institutional standard).
• Evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension, uncontrolled diabetes mellitus, active bleeding diatheses, or active infection, as determined by the investigator.
• Any condition that impairs a patient's ability to swallow whole pills. Presence of an active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of YL-17231, as determined by the investigator.
• History noninfectious pneumonitis required steroids treatment or concurrent pneumonitis or interstitial lung diseases.

Sponsors & Collaborators

• Shanghai YingLi Pharmaceutical Co. Ltd.: lead

Study Sites (3)

The Lindner Center for Research & Education at The Christ Hospital

Cincinnati, Ohio, 45219, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Huntsman Cancer Institute and Hospital, University of Utah

Salt Lake City, Utah, 84112, United States

RECRUITING

Central Study Contacts

David S. Hong, MD

CONTACT

(713) 563-1930; dshong@mdanderson.org

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: October 18, 2023
• First Posted: October 24, 2023
• Study Start: October 24, 2023
• Primary Completion: October 1, 2025
• Study Completion: April 1, 2026
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)