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This is a first-in-human (FIH), multicenter, non-randomized, openlabel, phase 1 study of ABSK112 in patients with NSCLC to evaluate the safety, tolerability, PK, and preliminary antitumor efficacy.
Full description
The study will be started with a dose escalation part of ABSK112 administered in repeated 28-day cycles in patients with NSCLC. The expansion part of oral ABSK112 at the recommended dose of expansion (RDE) will be followed to evaluate safety, tolerability, and preliminary antitumor activity among patients with locally advanced or metastatic NSCLC harboring EGFR Exon20ins.
Enrollment
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Inclusion criteria
Patients should understand, sign, and date the written informed consent form prior to screening.
Male or female aged 18 years or older.
Patients with histologically or cytologically confirmed locally advanced (and not a candidate for definitive therapy) or metastatic NSCLC.
Cohort-specific inclusion criteria:
Patients must have at least one measurable target lesion according to RECIST v1.1
ECOG performance status 0 or 1
Adequate organ function and bone marrow function.
Electrolyte: magnesium within 0.85 to 1.25 × institutional normal limits, sodium ≥130 mmol/L, potassium within institutional normal limits
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.
For patients participating in food effect exploration part:
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.
Exclusion criteria
Known allergy or hypersensitivity to any component of the investigational product.
NSCLC patients with EGFR Cys797Ser (C797S) mutation.
Cohort-specific exclusion criteria.
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.
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.
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.
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.
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.
Note: Refer to inclusion criteria regarding hypertension.
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.
Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging) or leptomeningeal disease (symptomatic or asymptomatic).
Impaired cardiac function or clinically significant cardiac disease.
Known acquired immunodeficiency syndrome (AIDS)-related illness, or positive test for HIV 1/2 antibody.
Exclusion of hepatitis infection based on the following results and/or criteria:
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.
Current evidence of radiation pneumonitis that required steroid treatment or unresolved drug-related pneumonitis, or current evidence or history of interstitial lung disease (ILD).
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.
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).
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
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.
Planned major surgery during study treatment.
Primary purpose
Allocation
Interventional model
Masking
164 participants in 1 patient group
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Central trial contact
Yinan Lin; Yuan Lu
Data sourced from clinicaltrials.gov
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