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

Abbisko Therapeutics

Status and phase: Enrolling; Phase 1

Conditions: Neoplasms; Tenosynovial Giant Cell Tumor

Treatments: Drug: ABSK021

Study type: Interventional

Funder types: Industry

Identifiers

NCT04192344

ABSK021-101

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 276 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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) :

1. 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);
2. Measurable disease as defined by RECIST 1.1 (except that a minimal size of 2 cm is required), assessed from MRI scans;
3. 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) :

1. Known allergy or hypersensitivity to any component of the investigational drug product
2. For expansion part, previous treatment with CSF 1/CSF 1R pathway inhibitors (not applicable for TGCT patients in US）
3. Others

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Sequential Assignment

Masking: None (Open label)

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276 participants in 1 patient group

ABSK021

Experimental group

Description:

Dose escalation of oral ABSK021 with a starting dose of 25mg once daily will be guided by"3+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.

Treatment:

Drug: ABSK021