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

Eligibility 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.
• 4. Cohort-specific
• 1. Known allergy or hypersensitivity to any component of the investigational product.
• 2. NSCLC patients with EGFR Cys797Ser (C797S) mutation.
• 3. Cohort-specific exclusion criteria.
• 4. Have been diagnosed with another primary malignancy other than NSCLC except for adequately treated non-melanoma skin cancer or cervical cancer in situ; definitively treated non-metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• 5. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting GI function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction, or current evidence of GI disease that present with diarrhea. If any of these conditions exist, the sites' staff should discuss with the sponsor to determine patient eligibility.
• 6. Previous anti-cancer therapy, including chemotherapy, radiotherapy, molecular targeted therapy, antibody therapy or other investigational drugs received ≤4 weeks prior to initiation of study treatment.
• 7. Major surgery within 4 weeks prior to the first dose of study drug. Or any surgical wound is infected, dehisced, or not completely healed before the screening.
• 8. Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy that have not regressed to Grade ≤1 severity (CTCAE v5.0) with the exception of which eligibility criteria allows, or alopecia, vitiligo, hypothyroidism stable on hormone replacement, or Grade 2 peripheral neurotoxicity.
• 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.