Clinical trial NCT04192344: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neoplasms
Tenosynovial Giant Cell Tumor
Keywords: Tenosynovial Giant Cell Tumor
TGCT
Solid tumors
Lead sponsor: Abbisko Therapeutics Co, Ltd
Sponsor class: INDUSTRY
First posted: 2019-12-10
Enrollment: 276
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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) :

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

Primary outcomes:
measure: Incidence of DLTs
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Incidence and Severity of AEs
timeFrame: Through study completion, an average of 6 months
Secondary outcomes:
measure: PFS
timeFrame: From date of enrollment until the date of first documented progression or death, assessed up to 12 months
measure: DoR
timeFrame: From date of enrollment until the date of first documented progression or death, assessed up to 12 months
measure: DCR
timeFrame: 24 weeks post-dose
measure: Cmax
timeFrame: Pre-dose and multiple timepoints (up to 72 hours) post-dose
measure: tmax
timeFrame: Pre-dose and multiple timepoints (up to 72 hours) post-dose
measure: Bioavailability
timeFrame: Pre-dose and multiple timepoints (up to 72 hours) post-dose
measure: Elimination half-life
timeFrame: Pre-dose and multiple timepoints (up to 72 hours) post-dose
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Precision NextGen Oncology
state: California
city: Denver
country: United States
facility: SCRI at HealthOne
state: Colorado
city: Atlanta
country: United States
facility: The Winship Cancer Institute of Emory University
state: Georgia
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Beijing
country: China
facility: Beijing Jishuitan Hospital
state: Beijing
city: Guangdong
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
state: Guangzhou
city: Shijiazhuang
country: China
facility: Hebei Medical University Third Hospital
state: Hebei
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou Universtity
state: Henan
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital
state: Liaoning
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital
state: Shanghai
city: Xian
country: China
facility: Xi'an Hong Hui Hospital
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Siqing Fu, MD
role: PRINCIPAL_INVESTIGATOR
References: