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

Phase 3Active Not RecruitingNCT05208047

Cogent Biosciences, Inc.442 enrolled

Overview

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 442 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 the potential 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. Additionally, a drug-drug interactions substudy will investigate the potential for CGT9486 to be a CYP3A4 inducer in approximately 16 patients who have received at least one prior line of therapy for GIST.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

442

Conditions

Advanced Gastrointestinal Stromal Tumors Metastatic Cancer

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: 1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST. Molecular pathology report must be available for Part 2; if molecular pathology report is unavailable or inadequate, an archival or fresh tumor tissue sample will be required to evaluate mutational status prior to randomization. 2. Documented disease progression on or intolerance to imatinib 3. Subjects must have received the following treatment: DDI Substudy/Part 1a: Treatment with ≥1 prior lines of therapy for GIST Part 1b: Treatment with ≥2 prior TKI for GISTs Part 2: Prior treatment with imatinib only 4. Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part 2) 5. ECOG - 0 to 2 6. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits Key Exclusion Criteria: 1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency 2. Clinically significant cardiac disease 3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug 4. Gastrointestinal abnormalities including, but not limited to, significant nausea and vomiting, malabsorption, external biliary shunt, or significant bowel resection that would preclude adequate absorption 5. Any active bleeding excluding hemorrhoidal or gum bleeding 6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody. 7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening 8. Received strong CYP3A4 inhibitors or inducers 9. Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)

Outcomes

Primary Outcomes

Part 1a - pharmacokinetics - Cmax

Maximum plasma concentration (Cmax)

Time frame: 16 days

Part 1a - pharmacokinetics - AUC

Area under the plasma concentration-time curve (AUC)

Time frame: 16 days

Part 1b - pharmacokinetics - Cmax

Maximum plasma concentration (Cmax)

Time frame: 14 days

Part 1b - pharmacokinetics - AUC

Area under the plasma concentration-time curve (AUC)

Time frame: 14 days

Part 1b - pharmacokinetics - Tmax

Time to maximum observed plasma concentration (Tmax)

Time frame: 14 days

Part 2 - Progression Free Survival (PFS)

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

Time frame: Approximately 48 months

DDI Substudy - pharmacokinetics - AUC

Area under the plasma concentration-time curve (AUC)

Time frame: 16 days

DDI Substudy - pharmacokinetics - Cmax

Maximum plasma concentration (Cmax)

Time frame: 14 days

Secondary Outcomes

All Study Parts - observing the safety of each treatment regimen.

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

Time frame: Approximately 48 months

All Study Parts - observing the safety of each treatment regimen.

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

Time frame: Approximately 48 months

All Study Parts - observing the safety of each treatment regimen.

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

Time frame: Approximately 48 months

All Study Parts - observing the safety of each treatment regimen.

Change from baseline in laboratory results

Time frame: Approximately 48 months

Part 1a, Part 1b, Part 2 - Overall Survival (OS)

Time from first dose to death due to any cause

Time frame: Approximately 48 months

Part 1a, Part 1b, Part 2 - Objective Response Rate (ORR)

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

Time frame: Approximately 48 months

Part 1a, Part 1b, Part 2 - Disease Control Rate (DCR)

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

Time frame: Approximately 48 months

Part 1a, Part 1b. Part 2 - Time to response (TTR)

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

Time frame: Approximately 48 months

Part 1a, Part 1b, Part 2 - Duration of Response (DOR)

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

Time frame: Approximately 48 months

Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30)

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.

Time frame: Approximately 48 months

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

Overview

Conditions

Interventions

Eligibility

Locations (110)

Outcomes

Primary Outcomes

Secondary Outcomes