Phase 3 Randomized Double-Blind Placebo-Controlled Multicenter Study of ABSK021 Hydrochloride Hydrate in Tenosynovial Giant Cell Tumor Patients

The primary objective of this study is to compare the **Objective Response Rate (ORR)** within 25 weeks after treatment with ABSK021 or placebo in patients with **Tenosynovial Giant Cell Tumor (TGCT)** based on **RECIST 1.1** criteria. This objective is clinically relevant as it aims to evaluate the efficacy of ABSK021 in reducing tumor size, which is a critical factor in assessing the potential therapeutic benefit for patients with TGCT.

Secondary objectives include:

• Comparing the ORR within 25 weeks after treatment with ABSK021 or placebo in TGCT patients based on **Tumor Volume Score (TVS)**.
• Comparing the effects of ABSK021 and placebo on the **Range of Motion (ROM)** in TGCT patients at Week 25.
• Comparing the effects of ABSK021 and placebo on **Patient Reported Outcome (PRO)** in TGCT patients at Week 25.
• Comparing the **Duration of Response (DOR)** after treatment with ABSK021 or placebo in TGCT patients based on RECIST 1.1 and TVS, respectively.
• Comparing the safety of ABSK021 and placebo in TGCT patients.
• Evaluating the **pharmacokinetic (PK) profile** of oral ABSK021.

The clinical trial involves a total of **65 participants** diagnosed with **Tenosynovial Giant Cell Tumor** (TGCT). The study population includes both male and female subjects, aged 18 years and older, who have a histologically confirmed TGCT that is not amenable to surgery. Participants were selected based on their ability to understand study procedures and provide informed consent, as well as their measurable disease status as defined by RECIST 1.1, with at least one lesion of 2 cm or greater. The trial population includes individuals with a stable prescription of analgesics, if needed, and those who have completed stiffness and pain scales during the screening period. Participants are required to have adequate organ and bone marrow function. The study also considers vulnerable populations, ensuring comprehensive representation. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 3**, randomized, double-blind, placebo-controlled, multicenter study designed to assess the efficacy and safety of ABSK021 in patients with **Tenosynovial Giant Cell Tumor** (TGCT). The primary objective is to compare the Objective Response Rate (ORR) within 25 weeks after treatment with ABSK021 or placebo, based on RECIST 1.1 criteria. The trial is expected to run from August 15, 2023, to April 30, 2027, with a maximum treatment period of 48 weeks for participants. The study involves the administration of ABSK021 in capsule form, with a maximum daily dose of 50 mg and a total dose not exceeding 73,000 mg.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), histologically confirmed TGCT not amenable to surgery, measurable disease, stable analgesic regimen, and adequate organ and bone marrow function. Following randomization, participants will receive either ABSK021 or placebo orally. Follow-up visits will occur regularly to monitor safety, efficacy, and any changes in symptoms, including range of motion, stiffness, and pain. The primary endpoint is the 25-week ORR by a Blinded Independent Review Committee, with secondary endpoints including changes in range of motion, stiffness, pain, and quality of life scores.

The end-of-study visit will conclude the participant's involvement, assessing the overall response and any long-term effects. Participants may be withdrawn from the study early due to adverse events, non-compliance with study procedures, or withdrawal of consent. The trial's design ensures rigorous evaluation of ABSK021's therapeutic potential while maintaining participant safety and data integrity.

The clinical trial involves the administration of **ABSK021**, an investigational medication, to evaluate its efficacy and safety in patients with **Tenosynovial Giant Cell Tumor** (TGCT). **ABSK021** is formulated as a capsule and contains the active substance **ABSK021 hydrochloride hydrate**. The medication is administered orally. The maximum daily dose is 50 mg, with a total maximum dose of 73,000 mg over a treatment period of up to 48 weeks. The compound is a synthetic small molecule developed by Abbisko Therapeutics Co., Ltd. Compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The study also includes a **placebo** group to serve as a comparator for assessing the efficacy of **ABSK021**. The placebo is administered in a manner identical to the experimental medication, ensuring the study remains double-blind. The placebo is provided in a form that matches the capsule appearance of **ABSK021** to maintain blinding integrity. Participants are randomly assigned to either the **ABSK021** or placebo group, and the objective response rate is evaluated based on RECIST 1.1 criteria within 25 weeks of treatment initiation.

The efficacy of the investigational product ABSK021 in the treatment of **Tenosynovial Giant Cell Tumor (TGCT)** will be assessed through a series of predefined endpoints. The primary endpoint is the 25-week Objective Response Rate (ORR) as evaluated by a Blinded Independent Review Committee (BIRC) using the RECIST 1.1 criteria. This will provide a standardized measure of tumor response to the treatment.

Secondary endpoints include the 25-week ORR based on Tumor Volume Score (TVS), and mean changes from baseline in several patient-reported outcomes at Week 25. These outcomes include the Range of Motion (ROM) of the affected joint, the Worst Stiffness Numeric Rating Scale (NRS) score, the Worst Pain NRS score, the Patient-reported Outcomes Measurement Information System (PROMIS) Physical Functioning score, and the EuroQol visual analogue scale (VAS) score. Additionally, the Duration of Response (DOR) will be assessed by BIRC based on both RECIST 1.1 and TVS.