Study of Pimicotinib (ABSK021) for Tenosynovial Giant Cell Tumor (MANEUVER)

A Phase 3, Randomized, Double-blind, Placebo-Controlled, Multicenter Study of ABSK021 to Assess the Efficacy and Safety in Patients With Tenosynovial Giant Cell Tumor

The goal of this clinical trial is to assess the efficacy and safety of Pimicotinib (ABSK021) in patients with Tenosynovial Giant Cell Tumor (TGCT). The main questions it aims to answer are:

• Whether the Pimicotinib(ABSK021) works well in patients with TGCT.
• Whether the Pimicotinib(ABSK021) is safe in patients with TGCT.

Participants will be asked to complete the study procedures:

• Receive the administration of Pimicotinib(ABSK021) or placebo (a placebo is a look-alike substance that contains no active drug) about 24 weeks in study part 1.
• Receive the administration of Pimicotinib(ABSK021) about 24 weeks in study part 2.
• Receive the administration of Pimicotinib(ABSK021) till study end in study part 3.
• Complete the study procedures speficied in the protocol, which is guided by researchers.

Study Overview

• Status: Active, not recruiting
• Conditions: Tenosynovial Giant Cell Tumor; Giant Cell Tumor of Tendon Sheath; Pigmented Villonodular Synovitis
• Intervention / Treatment: Drug: Placebo; Drug: Pimicotinib(ABSK021)

Detailed Description

This study consists of part 1 and part 2. Part 1 is a double-blind phase, eligible patients will be randomized to Pimicotinib(ABSK021) treatment group or matching placebo group and will receive Pimicotinib(ABSK021) or matching placebo until completion of Part 1.

Part 2 is an open-label treatment phase, and all patients entering this phase will receive open-label Pimicotinib(ABSK021) until completion of 24 weeks of dosing or withdrawal from the study.

Part 3 is an open-label extension treatment phase, and patients who completed the part 2 and continuted to be eligible, will go to the Part 3. Patients will receive the open-label Pimicotinib(ABSK021) until all patients withdraw from the study, or the sponsor decides to terminate the study, whichever occurs first.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: YUAN LU; Phone Number: +86-21-68910052; Email: clinical@abbisko.cn

Study Locations

• Canada
  • Montréal, Canada
    • McGill University Health center
  • Toronto, Canada
    • Princess Margaret Cancer Center
• China
  • Beijing, China
    • BeiJing JiShuiTan Hospital
  • Anhui
    • Bengbu, Anhui, China
      • The First Affiliated Hospital of Bengbu Medical College
  • Beijing
    • Beijing, Beijing, China
      • Peking University People's Hospital
  • Fujian
    • Fuzhou, Fujian, China
      • The First Affiliated Hospital Of Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • Guangdong Provincial People's Hospital
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Jinan University
  • Guizhou
    • Guiyang, Guizhou, China
      • The Affiliated Hospital of Guizhou Medical University
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
  • Hubei
    • Enshi, Hubei, China
      • The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture
    • Wuhan, Hubei, China
      • Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital Of Central South University
    • Changsha, Hunan, China
      • Hunan Provincial People's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Nanjing Drum Tower hospital
  • Liaoning
    • Shenyang, Liaoning, China
      • Liaoning Cancer Hospital&Institute
  • Shandong
    • Weifang, Shandong, China
      • Weifang people's Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai General Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • The Second Hospital of Shanxi Medical University
    • Xi'an, Shanxi, China
      • Xi'an Honghui Hospital
  • Wuhan
    • Chengdu, Wuhan, China
      • West China Hospital Sichuan University
  • Xinjiang
    • Ürümqi, Xinjiang, China
      • The first affiliated hospital of Xinjiang medical university
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • The Second Affiliated Hospital Zhejiang University School of Medicine
• Italy
  • Bologna, Italy
    • IRCCS Istituto Ortopedico Rizzoli
  • Milano, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Prato, Italy
    • Ospedale di Prato
• Netherlands
  • Leiden, Netherlands, 2333
    • Leiden University Medical Center
• Poland
  • Warsaw, Poland
    • Maria Sklodowska-Curie National Research Institute of Oncology
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
• United States
  • California
    • Beverly Hills, California, United States, 90212
      • Precision NextGen Oncology
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic Foundation
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas M.D. Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients should understand the study procedures and sign the informed consent form prior to screening.
• Age ≥ 18 years.
• A histologically confirmed TGCT with unresectable.
• Measurable disease as defined by RECIST 1.1, and with at least one lesion of ≥ 2 cm.
• Stable prescription of analgesic regimen for patients with an analgesic need.
• Participants should complete stiffness and pain scales during the screening period, and symptomatic disease because of active TGCT should meet minimum requirements as outlined in study protocol.
• ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1.
• Adequate organ function and bone marrow function.

Exclusion Criteria:

• Known allergy or hypersensitivity to any components of the investigational drug product.
• Previous treatment with highly selective inhibitors targeting CSF-1/CSF-1R. Previous therapy with imatinib and nilotinib is allowed.
• Known additional malignancy that required active treatment and may affect the patient's participation in the study or affect the outcome of the study as assessed by the Investigator.
• Known metastatic TGCT.
• Significant concomitant arthropathy in the affected joint, serious disease, uncontrolled infection.
• Known MRI contraindications.
• Has factors that significantly affected the absorption of oral drug.
• Major surgery or previous anti-tumor therapy for TGCT within 4 weeks prior to randomization.
• Concomitant use of strong CYP inhibitors or inducers as outlined in study protocol.
• Impaired cardiac function or clinically significant cardiac disease.
• Known active human immunodeficiency virus, active hepatitis B, active hepatitis C, or known active tuberculosis.
• Known active liver or biliary disease, or other diseases that may lead to abnormal liver function test results during the study.
• Pregnant or lactating women.
• Childbearing potential males or non-surgically sterilized female patients must agree to use effective methods of contraception during the study.
• Any other clinically significant comorbidities, which in the judgment of the Investigator, could compromise compliance with the protocol, interfere with the interpretation of study results, or predispose the patient to safety risks.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1/Part 2/Part 3- Pimicotinib(ABSK021)/ Pimicotinib(ABSK021); Participants receive the blinded treatment of ABSK021 for 24 weeks in Part 1 and continue on the open-label Pimicotinib(ABSK021) in Part 2 and Part 3.	Drug: Pimicotinib(ABSK021); capsule
Placebo Comparator: Part 1- Placebo/ Pimicotinib(ABSK021); Participants receive the blinded treatment of matching placebo for 24 weeks in Part 1 and have option to receive the open-label Pimicotinib(ABSK021) in Part 2.	Drug: Placebo; capsule; Drug: Pimicotinib(ABSK021); capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Assessed by central read using Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1)	Baseline to Week 25

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) per Tumor Volume Score (TVS)	Assessed by central read using Tumor Volume Score (TVS). TVS is a semi-quantitative MRI scoring system that describes tumor mass and is based on 10% increments of the estimated volume of the maximally distended synovial cavity or tendon sheath involved. A tumor that is equal in volume to that of a maximally distended synovial cavity or tendon sheath was scored 10; a score of 0 indicated no evidence of tumor.	Baseline to Week 25
Range of Motion (ROM)	Mean change from baseline in ROM of the affected joint	Baseline to Week 25
Worst Stiffness	Mean change from baseline in the Worst Stiffness Numeric Rating Scale (NRS) score at Week 25. The Worst Stiffness Numeric Rating Scale (NRS) was a 1-item, self-administered questionnaire assessing the "worst" stiffness in the last 24 hours. The NRS for this item ranged from 0 (no stiffness) to 10 (stiffness as bad as you can imagine). Higher scores mean a worse outcomes.	Baseline to Week 25
Worst Pain	Mean change from baseline in the Worst Pain Numeric Rating Scale (NRS) score at Week 25. The Worst Pain Numeric Rating Scale Score (NRS) was a 1-item, self-administered questionnaire assessing the "worst" pain in the last 24 hours. The NRS for this item ranged from 0 (no pain) to 10 (pain as bad as you can imagine). Higher scores mean a worse outcomes.	Baseline to Week 25
Physical Function	Mean change from baseline in the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Function score at Week 25. The Patient-reported Outcomes Measurement Information System (PROMIS) physical function scale was used to assess physical function of the upper and lower limbs. The scale ranged from 1 defined as 'unable to do' or 'cannot do' to 5 defined as 'without any difficulty' or 'not at all', where higher scores represent better outcomes.	Baseline to Week 25
Quality of life (QoL)	Mean change from baseline in EuroQol visual analogue scale (VAS) score at Week 25. The EuroQol visual analogue scale (VAS) is a Visual Analogue Scale on which the patient rates their current health, with 0 representing the "worst health you can imagine" and 100 representing the "best health you can imagine". Higher scores mean a better outcomes.	Baseline to Week 25
Duration of Response (DOR)	Duration of Response as measured by RECIST Version 1.1 and Tumor Volume Score (TVS)	The time (months) from the first documentation of objective response to the first documentation of radiographic disease progression (PD) or death due to any cause, whichever occurs first, assessed up to 24 months.

Collaborators and Investigators

• Sponsor: Abbisko Therapeutics Co, Ltd

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2023
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 13, 2023
• First Submitted That Met QC Criteria: April 5, 2023
• First Posted (Actual): April 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Tendinopathy; Neoplasms; Synovitis; Giant Cell Tumors; Giant Cell Tumor of Tendon Sheath; Synovitis, Pigmented Villonodular
• Other Study ID Numbers: ABSK021-301

Drug and device information, study documents

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