Neoplasms

Digestive System Diseases

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Gastrointestinal Stromal Tumors

Sarcoma

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Soft Tissue Sarcoma

Antineoplastic Agents

All Drugs and Chemicals

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Bezuclastinib 600 mg (tablet) administered orally daily Sunitinib 37.5 mg administered orally daily

Patients will begin bezuclastinib and add sunitinib 2 weeks later. Each cycle is 28 days.

Bezuclastinib in combination with sunitinib (sutent)

Bezuclastinib in combination with sunitinib

SARC Office

Candace Haddox, MD

Andrew Wagner, MD, PhD

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib.

This is an open label, single arm, phase 2 trial investigating bezuclastinib plus sunitinib in patients with GIST who have previously progressed on sunitinib. After washout, patients will begin bezuclastinib and add sunitinib 2 weeks later. Patients will continue on treatment until progression, unacceptable toxicity, or withdrawal of consent. Patients may stay on treatment beyond progression if there is clinical benefit in the opinion of the investigator. Imaging response assessments will be performed every 8 weeks until the participant reaches 15 months on study. After 15 months, response assessments may be performed every 3 months. Circulating tumor DNA (ctDNA) will be collected at baseline, with sequential initiation of bezuclastinib and sunitinib, at the first response assessment, and at the time of progression. In a subset of 20 patients, PET/CT will be performed at baseline and with sequential initiation of bezuclastinib and sunitinib, and tumor biopsies will be performed on cycle 2 day 1 for correlative studies. EORTC QLQ-C30 will be administered during the study to assess patient-reported quality of life.

SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST

A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST Who Progressed on Sunitinib Monotherapy

mPFS will be summarized with a Kaplan-Meier curve

Quality of life will be evaluated using the EORTC-QLQ-C30 with descriptive statistics reported at each timepoint. Changes in quality-of-life measures based on the EORTC-QLQ-C30 will be determined (difference at follow-up and baseline will be summarized). Changes in on-treatment scores compared to baseline will be analyzed to determine patients' perception of their functional status, symptoms, and overall health.

Cogent Biosciences, Inc.

Dana-Farber Cancer Institute

The Life Raft Group

Sarcoma Alliance for Research through Collaboration

Symptoms and General Pathology

Neoplasm Metastasis

Tin Fluorides

Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.

CGT9486 plus sunitinib

Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.

CGT9486

Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.

Participants will receive sunitinib orally until study stopping rules are met.

Cogent Biosciences

Jessica Sachs, MD

This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination with sunitinib. This is a multi-part study that will enroll approximately 426 patients. Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of CGT9486 to be used in subsequent parts in approximately 20 patients who have received at least one prior line of therapy for GIST and 2) evaluating for drug-drug interactions between CGT9486 and sunitinib in approximately 18 patients who have received at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the study will enroll approximately 388 patients who are intolerant to, or who failed prior treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to sunitinib alone with patients being randomized in a 1:1 manner.

This is a multi-part study: Part 1a is a single-arm design, Part 1b is a two-arm parallel design drug-drug interaction evaluation in the first treatment cycle and single-arm design in subsequent treatment cycles, and Part 2 is a randomized two-arm parallel comparator study

(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors

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

Area under the plasma concentration-time curve (AUC)

Time to maximum observed plasma concentration (Tmax)

Time from first dose to documented disease progression or death due to any cause, whichever occurs first

Incidence and severity of Adverse Events from first dose of study drug

Incidence and severity of Serious Adverse Events from first dose of study drug

Incidence of Adverse Events leading to dose modifications from first dose of study drug

Change from baseline in laboratory results

Time from first dose to death due to any cause

Percentage of subjects who achieved documented complete response (CR) + confirmed partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks

Time from first dose to first documented response based on modified Response Evaluation Criteria in Solid Tumors Version 1.1

Time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first

Change in individual scores in patients with locally advanced, unresectable, or metastatic GIST treated with CGT9486 in combination with sunitinib compared with patients treated with sunitinib monotherapy. The scale comprises 30 questions, 24 of which are aggregated into 9 multi-item scales, to include 5 functioning scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting) and 1 global health status scale. The remaining 6 single-item scales assess symptoms (dyspnea, appetite loss, sleep disturbance, constipation, diarrhea and the financial impact). All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning, while higher scores on the symptom and single-item scales indicate a higher level of symptoms.

Immune System Diseases

Blood and Lymph Conditions

Behaviors and Mental Disorders

Nervous System Diseases

Syndrome

Mastocytosis

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Leukemia, Myelomonocytic, Chronic

Leukemia, Myelomonocytic, Juvenile

Myelodysplastic Syndromes

Hypersensitivity

Skin Diseases

Hematologic Neoplasms

Myeloproliferative Disorders

Aggression

Soft Tissue Neoplasms

Urticaria

Hematologic Diseases

Mastocytosis, Systemic

Leukemia, Mast-Cell

Urticaria Pigmentosa

Immune Complex Diseases

Dementia

Aberrant Motor Behavior in Dementia

Behavioral Symptoms

Mast Cell Activation Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Myelomonocytic Leukemia

Juvenile Myelomonocytic Leukemia

Chronic Graft Versus Host Disease

Acute Graft Versus Host Disease

Chronic Myeloproliferative Disorders

Systemic Mastocytosis

Antigen-Antibody Complex

Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.

bezuclastinib

Hina Jolin, PharmD

Rachael Easton, MD, Ph.D.

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II is separated into two stages.

(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis

Incidence of AEs according to CTCAE version 5.0 or higher

Percentage change in plasma concentrations of bezuclastinib

Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood

0 -10 points (higher values represent worse symptom outcomes)

0 - 7 points (higher values represent better symptom outcomes)

0 - 100 (higher values represent better symptom outcomes)

0 - 252 (higher values represent worse symptom outcomes)

Bezuclastinib will be administered orally, once daily continuously for 28-day cycles

Bezuclastinib Tablets (Formulation A)

Bezuclastinib Tablets (Formulation B)

Placebo will be administered orally, once daily continuously for 28-day cycles

Placebo Tablets

Rachael Easton, MD, PhD

This is a multi-part, randomized, double-blind, placebo-controlled Phase 2 clinical study comparing the safety and efficacy of bezuclastinib (CGT9486) plus best supportive care (BSC) with placebo plus BSC in patients with nonadvanced systemic mastocytosis (NonAdvSM), including indolent systemic mastocytosis and smoldering systemic mastocytosis, whose symptoms are not adequately controlled by BSC. This study will be conducted in three parts. Patients in Parts 1a, 1b and 2 will receive bezuclastinib or placebo, and may roll over onto Part 3 to receive treatment with bezuclastinib.

In Part 1a and 1b of the study, patients with NonAdvSM will be randomly assigned to 1 of 2 dose levels of bezuclastinib plus BSC, or to placebo plus BSC. Upon analysis of the Part 1 data, a dose will be selected for Part 2. In Part 2, patients with NonAdvSM will be randomly assigned to the selected dose of bezuclastinib plus BSC, or to placebo plus BSC.

Patients who complete Part 1 or Part 2 may participate in Part 3 in which all patients will receive bezuclastinib plus BSC.

(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis

A Multi-Part, Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study of The Safety and Efficacy of CGT9486 in Subjects With Nonadvanced Systemic Mastocytosis

Selection of the recommended dose to be used in subsequent parts of the study.

Mean absolute change in a disease-specific patient reported outcome (PRO)

Scale of 0-100, higher numbers represent more severe impairment to quality of life.

Scale of 0-100, higher numbers represent better symptom outcomes

Response rate based on reduction in disease specific PRO

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
SARC044: A Phase II Trial of Bezuclastinib in Combination With Sunitinib in Patients With GIST	NCT06208748	Gastrointestina... GIST	Bezuclastinib i...	18 Years -	Sarcoma Alliance for Research through Collaboration
(Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors	NCT05208047	Advanced Gastro... Metastatic Canc...	CGT9486 plus su... CGT9486 Sunitinib Sunitinib	18 Years -	Cogent Biosciences, Inc.
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis	NCT04996875	Advanced System... SM With an Asso... Mast Cell Leuke... Aggressive Syst...	bezuclastinib	18 Years -	Cogent Biosciences, Inc.
(Summit) A Study to Evaluate the Efficacy and Safety of CGT9486 Versus Placebo in Patients With Indolent or Smoldering Systemic Mastocytosis	NCT05186753	SSM Mastocytosis, I... Mastocytosis, S... Mastocytosis	Bezuclastinib T... Bezuclastinib T... Placebo Tablets	18 Years -	Cogent Biosciences, Inc.

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