A Phase I/II Study of ABSK141 in Patients With Advanced Solid Tumors ( ABSK141-101 )

Exclusion Criteria22

• Known allergy or hypersensitivity to any component of the investigational product
• (For backfill cohorts and expansion part) Patients who were previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy
• Has a known additional malignancy that is progressing or has required active treatment
• Unable to swallow capsules or tablets 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. If any of these conditions exist, the site should discuss with the sponsor to determine patient eligibility
• Previous anti-tumor therapy, including chemotherapy, endocrine therapy, molecular targeted therapy or other investigational drugs received ≤2 weeks or ≤5-half life (whichever is shorter), radiotherapy and antibody therapy received ≤4 weeks prior to initiation of study treatment
• Major surgery within 4 weeks of the first dose of study drug. Note that all surgical wounds must be healed and free of infection or dehiscence
• Prior toxicities from chemotherapy, radiotherapy, and other anti-cancer therapies, including immunotherapy, that have not regressed to Grade ≤1 severity (CTCAE v5.0)
• Patients should not use proton pump inhibitors for at least 7 days prior to the first dose of ABSK141 and during treatment with ABSK141.
• P-gp inhibitor and strong CYP3A inhibitors to 7 days or 5 half-lives whichever is longer and for CYP3A inducers to 2 weeks or 5 half-lives
• Active central nervous system (CNS) metastases
• History of interstitial lung disease requiring systemic steroid treatment.
• Impaired cardiac function or clinically significant cardiac disease
• NSCLC cohorts: Patient previously identified as having a driver mutation (according to local standard of care or guidelines) and have not received any targeted therapy, for example: EGFR mutation, ALK rearrangement, KRAS G12C mutation, NTRK1/2/3 gene fusion, RET fusion, MET exon14 skipping mutation, BRAF V600E mutation, ROS1 rearrangement, etc
• Known acquired immunodeficiency syndrome (AIDS)-related illness, or positive test for HIV 1/2 antibody
• Exclusion of hepatitis infection
• Patients with refractory/uncontrolled ascites or pleural effusion
• Pregnant or nursing (lactating) women
• refuse to use highly effective methods of birth control during the study and for up to 6 months after the last dose of study drug.
• Sexually active males who refuse to use a condom during intercourse while taking drug and for 5 consecutive compound half-lives plus 60 days after stopping study drug.
• Vaccination with a live, attenuated vaccine within 4 weeks prior to the first dose of study treatment except for administration of inactivate vaccines
• Planned major surgery during study treatment
• Any other clinically significant comorbidities