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 toscreening.
2. Male or female aged 18 years or older.
3. Patients with histologically or cytologically confirmed locally advanced (and not acandidate for definitive therapy) or metastatic NSCLC.
4. Cohort-specific inclusion criteria:
5. For the escalation part (except for the RDE confirmation part), patients haveprogressed on, rejected, or are intolerant of standard therapy, or for whom nostandard therapy exists
6. For RDE confirmation in the escalation part: same as Cohort 1 in the expansionpart
7. For the expansion part, patients have documented EGFR in-frame exon 20 insertionmutations confirmed by certificated local laboratories; and must also meet allcriteria for the cohort in which their entry is proposed.
8. Patients must have at least one measurable target lesion according to RECIST v1.1
9. ECOG performance status 0 or 1
10. 7. Life expectancy ≥3 months
11. Adequate organ function and bone marrow function.
12. Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130mmol/L, potassium within institutional normal limits
13. Adequately controlled blood pressure (BP) with or without antihypertensivemedications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensivemedications within 1 week prior to the Cycle1 Day1.
14. For patients participating in food effect exploration part:
15. Be able to eat a standardized high-fat meal within 30 minutes
16. Be able to fast for 10 hours.
17. Non-surgically sterilized male or female patients of childbearing potential must agreeto use highly effective methods of birth control during the study treatment and forapproximately 6 months after the last dose of study drug. A condom is also required tobe used by vasectomized men to prevent delivery of the drug via seminal fluid.

Exclusion Criteria:

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 foradequately treated non-melanoma skin cancer or cervical cancer in situ; definitivelytreated non-metastatic prostate cancer; or patients with another primary malignancywho are definitively relapse-free with at least 3 years elapsed since the diagnosis ofthe other primary malignancy.
5. Unable to swallow capsules or malabsorption syndrome, disease significantly affectingGI function, or resection of the stomach or small bowel, symptomatic inflammatorybowel disease or ulcerative colitis, or partial or complete bowel obstruction, orcurrent evidence of GI disease that present with diarrhea. If any of these conditionsexist, the sites' staff should discuss with the sponsor to determine patienteligibility.
6. Previous anti-cancer therapy, including chemotherapy, radiotherapy, molecular targetedtherapy, antibody therapy or other investigational drugs received ≤4 weeks prior toinitiation of study treatment.
7. Major surgery within 4 weeks prior to the first dose of study drug. Or any surgicalwound 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) withthe exception of which eligibility criteria allows, or alopecia, vitiligo,hypothyroidism stable on hormone replacement, or Grade 2 peripheral neurotoxicity. Note: Refer to inclusion criteria regarding hypertension.
9. Potent moderate and strong inhibitors or inducers of CYP3A family within 2 weeksbefore the first dose of study treatment (3 weeks for St John's Wort); consumption ofgrapefruit juice, grapefruit hybrids, pomegranates, starfruits, pomelos, sevilleoranges 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 byradiographic 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 forHIV 1/2 antibody.
13. Exclusion of hepatitis infection based on the following results and/or criteria:
14. Active hepatitis B infection: positive tests for hepatitis B surface antigen (HbsAg), or antibody to hepatitis B core antigen (anti-HBc). A patient withpositive tests for HbsAg or anti-HBc but with HBV-DNA measurements lower thandetectable can be enrolled.
15. Active hepatitis C infection: positive Hepatitis C virus antibody. If positiveantibody to hepatitis C Virus (anti-HCV) is detected, Hepatitis C virus RNA bypolymerase chain reaction (PCR) is necessary. A patient with positive anti-HCVbut with a negative test for HCV RNA can be enrolled.
16. Patients with ascites or pleural effusion, or pericardial effusion which isrefractory/uncontrolled, or requiring the intervention within 2 weeks prior to thefirst dose.
17. Current evidence of radiation pneumonitis that required steroid treatment orunresolved drug-related pneumonitis, or current evidence or history of interstitiallung disease (ILD).
18. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of afemale after conception and until the termination of gestation, confirmed by apositive human chorionic gonadotropin (hCG) laboratory test within 7 days prior to thestart of study drug.
19. Vaccination with a live, attenuated vaccine within 4 weeks prior to the first dose ofstudy treatment except for administration of inactivate vaccines (e.g., COVID-19vaccines, inactivated influenza vaccines).
20. Current evidence or previous history of corneal pathology such as keratopathy, cornealabrasion or ulceration, or any other abnormal changes that may increase the risk ofcorneal toxicity during the study treatment
21. Any other clinically significant comorbidities, such as uncontrolled pulmonarydisease, active infection, or any other condition, which in the judgment ofinvestigators, could compromise compliance with the protocol, interfere with theinterpretation of study results, or predispose the patient to safety risks.
22. Planned major surgery during study treatment.