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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms; Tenosynovial Giant Cell Tumor
• Intervention / Treatment: Drug: ABSK021

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 Type: Interventional
• Enrollment (Estimated): 85
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Siqing Fu, MD; Phone Number: (713)792-4318; Email: siqingfu@mdanderson.org
• Study Contact Backup: Name: YUAN LU; Phone Number: +86-21-68910052; Email: clinical@abbisko.cn

Study Locations

• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Recruiting
      • Precision NextGen Oncology
      • Contact: Kamlesh Sankhala, MD; Email: info@nextgenonc.com
      • Contact: Phone Number: 1-424-777-0708
  • Colorado
    • Denver, Colorado, United States, 80218-1238
      • Completed
      • SCRI at Healthone
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Completed
      • The Winship Cancer Institute of Emory University
  • Texas
    • Houston, Texas, United States, 77030
      • Completed
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Abbisko Therapeutics Co, Ltd
• Investigators: Principal Investigator: Siqing Fu, MD, M.D. Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: December 9, 2019
• First Posted (Actual): December 10, 2019

Study Record Updates

• Last Update Posted (Actual): October 18, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Solid tumors; Tenosynovial Giant Cell Tumor; TGCT
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Tendinopathy; Synovitis; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath
• Other Study ID Numbers: ABSK021-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No