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

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ClinicalTrials.gov Identifier: NCT05208047
Recruitment Status : Recruiting
First Posted : January 26, 2022
Last Update Posted : April 4, 2024
Sponsor:
Information provided by (Responsible Party):
Cogent Biosciences, Inc.

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Advanced Gastrointestinal Stromal Tumors Metastatic Cancer Drug: CGT9486 plus sunitinib Drug: CGT9486 Drug: Sunitinib Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 426 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 14, 2022
Estimated Primary Completion Date : July 2025
Estimated Study Completion Date : September 2026

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1a
CGT9486 plus sunitinib 37.5 mg QD
 Drug: CGT9486 plus sunitinib
Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.
Experimental: Part 2 - Experimental Group
CGT9486 plus sunitinib 37.5 mg QD
 Drug: CGT9486 plus sunitinib
Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.
Active Comparator: Part 2 - Control Group
sunitinib 37.5 mg QD
 Drug: Sunitinib
Participants will receive sunitinib orally until study stopping rules are met.
Other Name: sunitinib - Part 2
Experimental: Part 1b - DDI Cohort 1
CGT9486 plus sunitinib 37.5 mg QD
 Drug: CGT9486
Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
Experimental: Part 1b - DDI Cohort 2
sunitinib 37.5 mg QD plus CGT9486
 Drug: Sunitinib
Participants will receive sunitinib until steady state then both sunitinib and CGT9486 orally until study stopping rules are met.
Other Name: sunitinib - Part 1b


Outcome Measures
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Primary Outcome Measures :
  1. Part 1a - pharmacokinetics - Cmax [ Time Frame: 16 days ]
    Maximum plasma concentration (Cmax)

  2. Part 1a - pharmacokinetics - AUC [ Time Frame: 16 days ]
    Area under the plasma concentration-time curve (AUC)

  3. Part 1b - pharmacokinetics - Cmax [ Time Frame: 14 days ]
    Maximum plasma concentration (Cmax)

  4. Part 1b - pharmacokinetics - AUC [ Time Frame: 14 days ]
    Area under the plasma concentration-time curve (AUC)

  5. Part 1b - pharmacokinetics - Tmax [ Time Frame: 14 days ]
    Time to maximum observed plasma concentration (Tmax)

  6. Part 2 - Progression Free Survival (PFS) [ Time Frame: Approximately 48 months ]
    Time from first dose to documented disease progression or death due to any cause, whichever occurs first


Secondary Outcome Measures :
  1. All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence and severity of Adverse Events from first dose of study drug

  2. All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence and severity of Serious Adverse Events from first dose of study drug

  3. All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Incidence of Adverse Events leading to dose modifications from first dose of study drug

  4. All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
    Change from baseline in laboratory results

  5. All Study Parts - Overall Survival (OS) [ Time Frame: Approximately 48 months ]
    Time from first dose to death due to any cause

  6. All Study Parts - Objective Response Rate (ORR) [ Time Frame: Approximately 48 months ]
    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

  7. All Study Parts - Disease Control Rate (DCR) [ Time Frame: Approximately 48 months ]
    Percentage of subjects who achieved CR + PR + stable disease (SD) at 16 weeks

  8. All Study Parts - Time to response (TTR) [ Time Frame: Approximately 48 months ]
    Time from first dose to first documented response based on modified Response Evaluation Criteria in Solid Tumors Version 1.1

  9. All Study Parts - Duration of Response (DOR) [ Time Frame: Approximately 48 months ]
    Time from first response (CR or PR) to the date of progression or death from any cause, whichever occurs first

  10. Part 2 Only - European Organisation for Research and Treatment of Cancer Quality of Life (EORTC-QLQ-30) [ Time Frame: Approximately 48 months ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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:

    • 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
  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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05208047


Contacts
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Contact: Cogent Biosciences 617-945-5576 peakinfo@cogentbio.com

Locations
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Sponsors and Collaborators
Cogent Biosciences, Inc.
Investigators
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Study Director: Jessica Sachs, MD Cogent Biosciences
More Information
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Responsible Party: Cogent Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT05208047    
Other Study ID Numbers: CGT9486-21-301
First Posted: January 26, 2022    Key Record Dates
Last Update Posted: April 4, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cogent Biosciences, Inc.:
Sunitinib
Solid Tumors
Gastrointestinal Stromal Tumors
Gastrointestinal
KIT
Kinase Inhibitors
Growth Inhibitors
 CGT9486
Unresectable
Metastatic
GIST
Bezuclastinib
PLX9486
Additional relevant MeSH terms:
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Gastrointestinal Stromal Tumors
Neoplasms
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Sunitinib
 Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action