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

• ClinicalTrials.gov Identifier: NCT04192344
• Recruitment Status: Recruiting
• First Posted: December 10, 2019
• Last Update Posted: July 27, 2022
• Sponsor: Abbisko Therapeutics Co, Ltd
• Information provided by (Responsible Party): Abbisko Therapeutics Co, Ltd

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neoplasms; Tenosynovial Giant Cell Tumor	Drug: ABSK021	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 85 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open-Label Study of ABSK021 to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced Solid Tumor
• Actual Study Start Date: January 20, 2020
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: ABSK021; 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.

Drug: ABSK021; ABSK021 oral capsule

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: YUAN LU; +86-21-68910052; clinical@abbisko.cn

Contact: Siqing Fu, MD; (713)792-4318; siqingfu@mdanderson.org

Locations

United States, Colorado

SCRI at HealthOne; Recruiting

Denver, Colorado, United States, 80218-1238

Contact: Gerald Falchook, MD

United States, Georgia

The Winship Cancer Institute of Emory University; Recruiting

Atlanta, Georgia, United States, 30322

Contact: Harvey R Donald, MD

United States, Texas

MD Anderson Cancer Center; Recruiting

Houston, Texas, United States, 77030

Contact: Munir H Chowdhury 713-792-4976 mchowdhury@mdanderson.org

Sponsors and Collaborators

Abbisko Therapeutics Co, Ltd

Investigators

• Principal Investigator: Siqing Fu, MD; M.D. Anderson Cancer Center

More Information

• Responsible Party: Abbisko Therapeutics Co, Ltd
• ClinicalTrials.gov Identifier: NCT04192344
• Other Study ID Numbers: ABSK021-101
• First Posted: December 10, 2019
• Last Update Posted: July 27, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Abbisko Therapeutics Co, Ltd:

Tenosynovial Giant Cell Tumor; TGCT; Solid tumors

Additional relevant MeSH terms:

Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Synovitis; Joint Diseases; Musculoskeletal Diseases; Tendinopathy; Muscular Diseases