A Phase 1, Study of YL-15293 in Subjects With Advanced Solid Tumors With a KRAS G12C Mutation

• Status: Not yet recruiting
• Trial end date: 2023-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a phase 1 / 2 open label multicenter study to evaluate the maximum tolerance, safety, tolerance and PK of oral yy-15293 in patients with advanced solid tumors with KRAS G12C mutation, so as to confirm the recommended phase 2 dose of yy-15293 and obtain the preliminary efficacy information of patients with advanced solid tumors with KRAS G12C mutation.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Shanghai YingLi Pharmaceutical Co. Ltd.

Criteria

Patients must meet all of the following inclusion criteria before they can be enrolled in this trial:

1. Age ≥ 18 years

2. Histologically and genomically confirmed locally advanced or metastatic malignant solid tumors with KRAS p.g12c mutation.

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 nivolumab or pembrolizumab if clinically applicable） C. Patients with solid tumors other than NSCLC or colorectal cancer should have received systematic treatment at least once.

3. It can provide core or excised biopsy tissue from archival tissue samples or newly obtained tumor lesions（Expansion phase only）

4. According to recist1.1 standard, there are measurable or evaluable tumor lesions

5. performance status，PS≤1

6. Estimated survival time > 3 months

7. QTcF ≤ 470 msec

8. 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）；Alkaline phosphatase < 2.0 x ULN (if there is liver or bone metastasis, < 3.0 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）

9. The elution period of macromolecular drugs is ≥ 4 weeks, and that of oral fluorouracil and small molecule targeted drugs is ≥ 2 weeks

10. Fertile women must have a negative blood pregnancy test within 72 hours before receiving the first study drug;

11. 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;

12. Did not participate in the clinical trial as a subject within 1 month before participating in the trial;

13. According to the judgment of the researcher, the compliance is high, willing to complete the test and can abide by the test scheme;

14. Voluntarily participate in this clinical trial, understand the research procedures and be able to sign the informed consent in writing.

Patients with any of the following items cannot be enrolled in this study:

1. Untreated patients with active brain metastases (except those with treated or asymptomatic brain metastases);

2. 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;

3. 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

4. Have a history of gastrointestinal diseases or gastric surgery or inability to swallow oral drugs

5. Active infection requiring treatment

6. 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.

7. 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

8. Allergic constitution, or known history of allergy to this drug component

9. 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.

10. CYP3A4 or P-gp strong inhibitors were used within 14 days before study enrollment

11. There is third space effusion that cannot be controlled by drainage or other methods (such as massive pleural effusion and ascites)

12. Have a clear history of neurological or mental disorders

13. The researchers believe that the subjects are not suitable to participate in this study for other reasons

In case of one or more of the following circumstances, the subject shall suspend the test:

1. Subjects asked to withdraw from the study;

2. Imaging evidence shows that the disease is progressing

3. Pregnancy events occurred during the study

4. After dose adjustment, the subject still could not tolerate the toxicity

5. The researcher considers it necessary to withdraw from the study