Phase I Clinical Study of YL-15293 in Patients With Advanced Solid Tumor With KRAS Mutation

NCT05173805 | Unknown Phase 1

• 1 other identifier: YL-15293-002
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 / 2 open label multicenter study to evaluate the maximum tolerance, safety, tolerance and PK of oral YL-15293 in patients with advanced solid tumors with KRAS mutation, so as to confirm the recommended phase 2 dose of YL-15293 and obtain the preliminary efficacy information of patients with advanced solid tumors with KRAS mutation.

Conditions

Advanced Solid Tumor

Keywords

with a KRAS mutation

Outcome Measures

Primary Outcomes (4)

• The overall response rate (ORR)

  The overall response rate (ORR) will be estimated based on the proportion of evaluable patients whose overall response (ORR) during study treatment is CR or PR. Disease response will be assessed by the investigator using RECIST v1.1.

  Throughout the study for approximately 2 years

• Progression free survival, PFS

  PFS, defined as the time from the first dose of study treatment to first

  Throughout the study for approximately 2 years

• Overall survival, OS

  The time from randomization to death for any reason

  Throughout the study for approximately 2 years

• Disease control rate, DCR

  The percentage of cases with remission (PR+CR) and stable lesions (SD) after treatment

  Throughout the study for approximately 2 years

Study Arms (1)

YL-15293

EXPERIMENTAL

Single arm, open, single and multiple doses; Dosage form: YL-15293 tablets Specification: 50mg, 200mg Storage conditions: refrigerated and sealed at 2-8℃ Way of administration: Single-dose study: Oral administration, once a day, with warm water, fasting administration, fasting 1 hour before and 2 hours after administration. Multiple administration studies: oral administration, warm water delivery, fasting administration, fasting 1 hour before administration and 2 hours after administration, continuous administration for 21 days as a treatment cycle. The way of taking the medicine is twice a day.

Drug: YL-15293

Interventions

YL-15293 DRUG

After enrollment, patients will receive oral YL-15293 twice a day until disease progression, unacceptable adverse events, concurrent diseases prevent further study treatment, the investigator decides to withdraw the patient, the patient withdraws consent, the patient is pregnant, or for administrative reasons. After treatment, the patients will continue to be followed up for 30 days. Patients who permanently stop the study treatment for reasons other than disease progression will be followed up for disease evaluation after treatment until the start of new anti-cancer treatment, withdrawal of consent, loss of follow-up, death or until the sponsor stops the study, whichever comes first.

YL-15293

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years
• For locally advanced or metastatic malignant solid tumors with KRAS mutations (including p.G12D, p.G12V, p.G12C, p.G12A) confirmed by histology and genomics, patients with KRAS p.G12C mutations are preferentially enrolled.
• A. For patients with NSCLC, previous first-line treatment based on platinum failed; B. For patients with colorectal cancer, at least two-line systemic treatment regimens have been experienced previously（Patients with colorectal cancer and high microsatellite instability must receive at least PD-1 or PD-L1 if clinically applicable） C. Patients with solid tumors other than NSCLC or colorectal cancer should have received systematic treatment at least once.
• According to recist1.1 standard, there are measurable or evaluable tumor lesions
• performance status，PS≤1
• Estimated survival time \> 3 months
• It has a good level of organ function A. Bone marrow function needs to meet：ANC≥1.5×109/L；PLT≥100×109/L；Hb≥9g/dL B. renal function：Cr≤1.5 times the upper limit of normal value；or Creatinine clearance≥50ml/min C. liver function：total bilirubin\<1.5 x ULN（For subjects with documented Gilbert syndrome,\< 2.0 x ULN or subjects with indirect bilirubin levels suggesting a source of extrahepatic elevation\<3.0 x ULN）；ALT and AST≤ 2.5 x ULN（If liver metastasis occurs≤ 5 x ULN） D. Coagulation function：Prothrombin time (PT) or partial thromboplastin time (PTT) \< 1.5 x upper normal limit (ULN), or international normalized ratio (INR) \< 1.5 or within the target range (if preventive anticoagulant therapy is performed） E). The corrected QT interval (QTcF) of Fridericia method is less than 450 ms for males and less than 470 ms for females.
• The elution period of macromolecular drugs is ≥ 4 weeks, and that of oral fluorouracil and small molecule targeted drugs is ≥ 2 weeks
• Fertile women must have a negative blood pregnancy test within 72 hours before receiving the first study drug;
• For fertile men and women, they must be willing to use appropriate contraceptive methods 30 days before the first study drug administration and 120 days after the last study drug administration;
• Did not participate in the clinical trial as a subject within 1 month before participating in the trial;
• According to the judgment of the researcher, the compliance is high, willing to complete the test and can abide by the test scheme;
• Voluntarily participate in this clinical trial, understand the research procedures and be able to sign the informed consent form in writing.

You may not qualify if:

• Patients with any of the following items cannot be enrolled in this study:
• Untreated patients with brain metastasis meet one or more of the following conditions：
• Need to use corticosteroids or dehydration treatment (except those with treated or asymptomatic brain metastases);
• There are significant clinical symptoms;
• The tumor stabilization time after radiotherapy or surgery should not exceed 4 weeks.
• (Except for patients with brain metastasis who have been treated or have no symptoms)
• Other malignant tumors in recent five years. Basal cell carcinoma of the skin, except squamous cell carcinoma of the skin or cervical carcinoma in situ after potential treatment;
• Myocardial infarction, symptomatic congestive heart failure (New York Heart Association \> grade II), unstable angina pectoris or arrhythmia requiring drug treatment occurred within 6 months before enrollment
• Have a history of gastrointestinal diseases or gastric surgery or inability to swallow oral drugs
• Active infection requiring treatment
• Patients with active hepatitis B (hepatitis B surface antigen and / or hepatitis B core antibody positive and HBV-DNA \> 103 copies /mL or 200IU/mL) or hepatitis C patients (hepatitis C virus positive and / or HCV-RNA positive) or HIV positive patients are required to receive treatment.
• Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks before the first use of the study drug, or elective surgery during the trial, or therapeutic or palliative radiotherapy within 2 weeks before the first use of the study drug
• Allergic constitution, or known history of allergy to this drug component
• According to the researchers' judgement, there are serious diseases that may endanger the safety of patients or affect the completion of research, such as uncontrollable hypertension, uncontrollable diabetes and thyroid diseases.
• There is fluid accumulation in the third space that cannot be controlled by drainage or other methods (such as massive identification and hydrothorax)

Sponsors & Collaborators

• Shanghai YingLi Pharmaceutical Co. Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangzhou, 510062, China

Location

Study Officials

• Li Zhang, PH D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 14, 2021
• First Posted: December 30, 2021
• Study Start: January 30, 2022
• Primary Completion: April 30, 2024
• Study Completion: December 30, 2024
• Last Updated: July 18, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)