(Peak) A Phase 3 Randomized, Open-label, Multicenter Clinical Study of CGT9486+Sunitinib vs Sunitinib in Subjects with Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors

The primary objective of this Phase 3 clinical study is to determine the **efficacy** of the combination of bezuclastinib and sunitinib compared to sunitinib alone in subjects with locally advanced, unresectable, or metastatic **gastrointestinal stromal tumors** (GIST). This is clinically relevant as it aims to assess whether the combination therapy can provide superior therapeutic benefits over the standard treatment with sunitinib, potentially leading to improved patient outcomes in this challenging condition.

Secondary objectives include evaluating the efficacy parameters of bezuclastinib combined with sunitinib versus sunitinib alone in subjects with GIST. This involves assessing various measures of treatment effectiveness to further understand the potential advantages of the combination therapy.

The clinical trial involves a total of **275 participants** diagnosed with **gastrointestinal stromal tumor** (GIST). The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on specific criteria, including a histologically confirmed diagnosis of locally advanced, metastatic, and/or unresectable GIST, and documented disease progression on or intolerance to imatinib. The trial includes individuals who have received prior treatment with imatinib, with at least one measurable lesion according to mRECIST v1.1, and an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2. The trial population is characterized by a diverse range of health statuses, and the inclusion of a vulnerable population is noted. Lifestyle factors such as diet and physical activity are not specified in the available data.

The clinical trial is a **randomized**, open-label, multicenter study designed to evaluate the efficacy of the combination of CGT9486 and **sunitinib** compared to sunitinib alone in subjects with locally advanced, unresectable, or metastatic **gastrointestinal stromal tumors** (GIST). The trial is structured in two parts, with the primary objective of determining the progression-free survival (PFS) as assessed by blinded independent central review (BICR) using mRECIST v1.1 criteria. Secondary endpoints include overall survival (OS) and overall response rate (ORR), also determined by BICR.

The trial is expected to span approximately three years, with an estimated recruitment start date of January 1, 2023, and an anticipated end date of September 29, 2026. Participants will be involved in the study for a maximum treatment period of 34 weeks. The study involves several key visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histologically confirmed GIST, documented disease progression on or intolerance to imatinib, and the presence of at least one measurable lesion. Follow-up visits will be conducted to monitor the participants' response to treatment and any adverse events. The end-of-study visit will conclude the participants' involvement, assessing the final outcomes and any long-term effects of the treatment.

Participants may be withdrawn from the study early if they experience unacceptable toxicity, disease progression, or if they withdraw consent. The trial is not categorized as low intervention and is classified as a Phase III study, aligning with EMA guidance on disclosure rules. The investigational product, CGT9486, is administered orally in tablet form, with a maximum daily dose of 600 mg, while sunitinib is provided as hard capsules with a maximum daily dose of 37.5 mg. The study aims to provide valuable insights into the treatment of GIST, potentially offering an improved therapeutic option for patients with this condition.

The clinical trial involves the administration of **CGT9486**, a small molecule tyrosine kinase inhibitor targeting KIT, in the form of a **tablet**. The active substance in CGT9486 is **3,4-dimethyl-N-(2-phenyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazole-5-carboxamide**, which is of chemical origin. The maximum daily dose of CGT9486 is 600 mg, with a total maximum dose of 620.5 g over a treatment period of 34 days. The medication is administered **orally**. Participant compliance with the dosing schedule will be monitored throughout the study.

In addition to CGT9486, the trial includes the administration of **Sunitinib**, a small molecule antineoplastic agent, in the form of **hard capsules**. The active substance is **Sunitinib**, and the maximum daily dose is 37.5 mg, with a total maximum dose of 38.78 g over the same treatment period of 34 days. Sunitinib is also administered **orally**. The trial aims to compare the efficacy of the combination of CGT9486 and Sunitinib against Sunitinib alone in subjects with locally advanced, unresectable, or metastatic **gastrointestinal stromal tumors** (GIST).

The efficacy of the investigational treatment in this clinical trial will be assessed using specific endpoints. The primary endpoint is **Progression-Free Survival (PFS)**, defined as the time from randomization to disease progression or death from any cause, whichever occurs first. This will be determined by Blinded Independent Central Review (BICR) using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) version 1.1. Secondary endpoints include **Overall Survival (OS)**, which is the time from randomization until the date of death, and **Objective Response Rate (ORR)**, also determined by BICR using mRECIST v1.1.