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

Official title

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

Overview

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

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.

Interventions

• Drug ABSK021
  ABSK021 oral capsule

Primary outcome measures

• Incidence of DLTs [Time frame: At the end of Cycle 1 (each cycle is 28 days)]
• Incidence and Severity of AEs [Time frame: Through study completion, an average of 6 months]

Secondary outcome measures (7)

• PFS [Time frame: From date of enrollment until the date of first documented progression or death, assessed up to 12 months]
• DoR [Time frame: From date of enrollment until the date of first documented progression or death, assessed up to 12 months]
• DCR [Time frame: 24 weeks post-dose]
• Cmax [Time frame: Pre-dose and multiple timepoints (up to 72 hours) post-dose]
• tmax [Time frame: Pre-dose and multiple timepoints (up to 72 hours) post-dose]
• Bioavailability [Time frame: Pre-dose and multiple timepoints (up to 72 hours) post-dose]
• Elimination half-life [Time frame: Pre-dose and multiple timepoints (up to 72 hours) post-dose]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 13 centers

• Beijing Jishuitan Hospital — Beijing
• The First Affiliated Hospital of Sun Yat-sen University — Guangdong
• Hebei Medical University Third Hospital — Shijiazhuang
• Henan Cancer Hospital — Zhengzhou
• The First Affiliated Hospital of Zhengzhou Universtity — Zhengzhou
• Jiangsu Province Hospital — Nanjing
• Nanjing Drum Tower Hospital — Nanjing
• Liaoning Cancer Hospital — Shenyang
• … and 5 more centers

United States · 4 centers

• Precision NextGen Oncology — Beverly Hills
• SCRI at HealthOne — Denver
• The Winship Cancer Institute of Emory University — Atlanta
• MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT04192344 · ABSK021-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗