A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-021 in Patients With Advanced Solid Tumor

Study Overview
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Brief Summary
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This is an open-label phase 1 study to determine the safety and tolebility of oral ABSK021 in patients with advanced solid tumor as well as the Recommended Phase 2 dose (RP2D) of oral ABSK021. Preliminary antitumor activity will also be assessed.

Detailed Description
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The study will start with a dose escalation part of single-agent ABSK021 administered in repeated 28-day cycles in patients with advanced solid for safety and tolerability. The expansion part of oral ABSK021 at recommended dose of expansion (RDE) will be followed for further evaluating safety and tolerability among selected tumor types. Preliminary antitumor activity will also be assessed.

Official Title
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A Phase 1, Open-Label Study of ABSK021 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Solid Tumor

Conditions
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Tenosynovial Giant Cell Tumor, Neoplasms

Intervention / Treatment
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* Drug: ABSK021


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed solid tumors that have progressed on or intolerant to standard therapy or whom no standard therapy exists ECOG (electrocorticogram) performance status 0 1 Life expectancy ≥ 3 months Adequate organ function and bone marrow function For patients with tenosynovial giant cell tumor (TGCT) : A diagnosis of TGCT [i ncluding pigmented villonodular synovitis (PVNS) or giant cell tumors of the tendon sheath (GCT TS) (i) that has been histologically confirmed either by a pathologist at the treating institution or a central pathologist, and (ii) where surgical resection would be associated with potentially worsening functional limitation or severe morbidity (locally advanced disease), with morbidity determined consensually by qualified personnel (eg, two surgeons or a multi disciplinary tumor board); Measurable disease as defined by RECIST 1.1 (except that a minimal size of 2 cm is required), assessed from MRI scans; Others Exclusion Criteria: Known allergy or hypersensitivity to any component of the investigational drug product Previous treatment with CSF-1(colony stimulating factor 1)/CSF-1R (colony stimulating factor 1 receptor) pathway inhibitors Known additional malignancy that is progressing or required active treatment within 3 years of the first dose of study treatment Inability to take oral medication or significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption of oral medication Previous anti-cancer therapy, including chemotherapy, radiotherapy, endocrine therapy or molecular targeted therapy within ≤ 5-halflife or ≤ 4 weeks (whichever is shorter) prior to initiation of study treatment (chemotherapy with nitrosourea or mitomycin should be 6 weeks prior to initiation of study treatment) Major surgery within 4 weeks of the first dose of study drug and 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 ≤2 severity (CTCAE v5.0) with the exception of alopecia and vitiligo Prior corticosteroids as anti-cancer therapy within a minimum of 2 weeks of the first dose of study drug Concomitant use of strong inhibitors or inducers of CYP3A4 Active central nervous system (CNS) metastases Impaired cardiac function or clinically significant cardiac disease Patients with Gilbert's Syndrome or other underlying conditions that may lead to a greater likelihood of developing LFT(liver function test) abnormalities during the study Known human immunodeficiency virus or active hepatitis B, or active hepatitis C infection Refractory/uncontrolled ascites or pleural effusion Pregnant or nursing For patients with tenosynovial giant cell tumor (TGCT) : Known allergy or hypersensitivity to any component of the investigational drug product For expansion part, previous treatment with CSF 1/CSF 1R pathway inhibitors (not applicable for TGCT patients in US） Others

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABSK021<br>Dose escalation of oral ABSK021 with a starting dose of 25mg once daily will be guided by3+3 escalation rules based on safety data until an MTD has been identified or a RDE. For each dose, patients will first receive a single dose ABSK021 tablet(s) by mouth at Day -3 and be followed by a 3-day off as a run-in period to access the safety and PK of single-dose. Then, patients will continuously receive ABSK021 once daily (QD) in repeated 28-day cycles. | Drug: ABSK021<br>* ABSK021 oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of DLTs | DLT(dose-limiting toxicity) | At the end of Cycle 1 (each cycle is 28 days) | 
| Incidence and Severity of AEs | Adverse events (AEs), adverse events of special interest (AESIs) and serious adverse events (SAEs) | Through study completion, an average of 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Progression-Free Survival (PFS) | From date of enrollment until the date of first documented progression or death, assessed up to 12 months | 
| DoR | Duration of Response (DoR) | From date of enrollment until the date of first documented progression or death, assessed up to 12 months | 
| DCR | Disease Control Rate (DCR) | 24 weeks post-dose | 
| Cmax | The peak plasma concentration of a drug after administration | Pre-dose and multiple timepoints (up to 72 hours) post-dose | 
| tmax | Time to reach Cmax | Pre-dose and multiple timepoints (up to 72 hours) post-dose | 
| Bioavailability | The systemically available fraction of a drug | Pre-dose and multiple timepoints (up to 72 hours) post-dose | 
| Elimination half-life | The time required for the concentration of the drug to reach half of its original value | Pre-dose and multiple timepoints (up to 72 hours) post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tenosynovial Giant Cell Tumor, TGCT, Solid tumors