A Study to Assess Safety, Tolerability, and Pharmacokinetics of ABSK112 in Patients With Non-Small Cell Lung Cancer

Inclusion Criteria

• •1. Patients should understand, sign, and date the written informed consent form prior to screening.
• •2. Male or female aged 18 years or older.
• •3. Patients with histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC.
• •1. For the escalation part (except for the RDE confirmation part), patients have progressed on, rejected, or are intolerant of standard therapy, or for whom no standard therapy exists
• •2. For RDE confirmation in the escalation part: same as Cohort 1 in the expansion part
• •3. For the expansion part, patients have documented EGFR in-frame exon 20 insertion mutations confirmed by certificated local laboratories; and must also meet all criteria for the cohort in which their entry is proposed.
• •5. Patients must have at least one measurable target lesion according to RECIST v1.1
• •6. ECOG performance status 0 or 1
• •7. 7\. Life expectancy ≥3 months
• •8. Adequate organ function and bone marrow function.
• •9. Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130 mmol/L, potassium within institutional normal limits
• •10. Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week prior to the Cycle1 Day1.
• •11. For patients participating in food effect exploration part:
• •1. Be able to eat a standardized high-fat meal within 30 minutes
• •2. Be able to fast for 10 hours.
• •12. Non-surgically sterilized male or female patients of childbearing potential must agree to use highly effective methods of birth control during the study treatment and for approximately 6 months after the last dose of study drug. A condom is also required to be used by vasectomized men to prevent delivery of the drug via seminal fluid.
• •9. Potent moderate and strong inhibitors or inducers of CYP3A family within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort); consumption of grapefruit juice, grapefruit hybrids, pomegranates, starfruits, pomelos, seville oranges or juice products within 3 days prior to the first dose of study treatment.
• •10. Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
• •11. Impaired cardiac function or clinically significant cardiac disease.
• •12. Known acquired immunodeficiency syndrome (AIDS)-related illness, or positive test for HIV 1/2 antibody.
• •13. Exclusion of hepatitis infection based on the following results and/or criteria:
• •1. Active hepatitis B infection: positive tests for hepatitis B surface antigen (HbsAg), or antibody to hepatitis B core antigen (anti-HBc). A patient with positive tests for HbsAg or anti-HBc but with HBV-DNA measurements lower than detectable can be enrolled.
• •2. Active hepatitis C infection: positive Hepatitis C virus antibody. If positive antibody to hepatitis C Virus (anti-HCV) is detected, Hepatitis C virus RNA by polymerase chain reaction (PCR) is necessary. A patient with positive anti-HCV but with a negative test for HCV RNA can be enrolled.
• •14. Patients with ascites or pleural effusion, or pericardial effusion which is refractory/uncontrolled, or requiring the intervention within 2 weeks prior to the first dose.
• •15. Current evidence of radiation pneumonitis that required steroid treatment or unresolved drug-related pneumonitis, or current evidence or history of interstitial lung disease (ILD).
• •16. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test within 7 days prior to the start of study drug.
• •17. Vaccination with a live, attenuated vaccine within 4 weeks prior to the first dose of study treatment except for administration of inactivate vaccines (e.g., COVID-19 vaccines, inactivated influenza vaccines).
• •18. Current evidence or previous history of corneal pathology such as keratopathy, corneal abrasion or ulceration, or any other abnormal changes that may increase the risk of corneal toxicity during the study treatment
• •19. Any other clinically significant comorbidities, such as uncontrolled pulmonary disease, active infection, or any other condition, which in the judgment of investigators, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.
• •20. Planned major surgery during study treatment.