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

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

Tracking Information

• First Submitted Date: December 23, 2021
• First Posted Date: January 26, 2022
• Last Update Posted Date: April 4, 2024
• Actual Study Start Date: April 14, 2022
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 16, 2022)

• Part 1a - pharmacokinetics - Cmax [ Time Frame: 16 days ]
  Maximum plasma concentration (Cmax)
• Part 1a - pharmacokinetics - AUC [ Time Frame: 16 days ]
  Area under the plasma concentration-time curve (AUC)
• Part 1b - pharmacokinetics - Cmax [ Time Frame: 14 days ]
  Maximum plasma concentration (Cmax)
• Part 1b - pharmacokinetics - AUC [ Time Frame: 14 days ]
  Area under the plasma concentration-time curve (AUC)
• Part 1b - pharmacokinetics - Tmax [ Time Frame: 14 days ]
  Time to maximum observed plasma concentration (Tmax)
• 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

Original Primary Outcome Measures (submitted: January 14, 2022)

• Part 1a - pharmacokinetics - Cmax [ Time Frame: 16 days ]
  Maximum plasma concentration (Cmax)
• Part 1a - pharmacokinetics - AUC [ Time Frame: 16 days ]
  Area under the plasma concentration-time curve (AUC)
• Part 1b - pharmacokinetics - Cmax [ Time Frame: 14 days ]
  Maximum plasma concentration (Cmax)
• Part 1b - pharmacokinetics - AUC [ Time Frame: 14 days ]
  Area under the plasma concentration-time curve (AUC)
• Part 1b - pharmacokinetics - Tmax [ Time Frame: 14 days ]
  Time to maximum observed plasma concentration (Tmax)
• Part 1b - pharmacokinetics - T1/2 [ Time Frame: 14 days ]
  Time to plasma concentration terminal half-life (T1/2)
• Part 1b - pharmacokinetics - CLss/F [ Time Frame: 14 days ]
  Apparent total body clearance at steady state (CLss/F)
• 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

Current Secondary Outcome Measures (submitted: May 16, 2022)

• 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
• 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
• 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
• All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
  Change from baseline in laboratory results
• All Study Parts - Overall Survival (OS) [ Time Frame: Approximately 48 months ]
  Time from first dose to death due to any cause
• 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
• 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
• 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
• 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
• 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.

Original Secondary Outcome Measures (submitted: January 14, 2022)

• 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
• 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
• 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
• All Study Parts - observing the safety of each treatment regimen. [ Time Frame: Approximately 48 months ]
  Change from baseline in laboratory results
• All Study Parts - Overall Survival (OS) [ Time Frame: Approximately 48 months ]
  Time from first dose to death due to any cause
• 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
• 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
• 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
• 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
• All Study Parts - Evaluating the effect of each treatment regimen on pharmacodynamic biomarkers [ Time Frame: Approximately 48 months ]
  Mutations in KIT and PDGFR genes measured in plasma
• All Study Parts - Evaluating the effect of each treatment regimen on pharmacodynamic biomarkers [ Time Frame: Approximately 48 months ]
  Determination of baseline genetic expression measured from peripheral blood to assess relationship with efficacy and safety outcomes
• 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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: (Peak) A Phase 3 Randomized Trial of CGT9486+Sunitinib vs. Sunitinib in Subjects With Gastrointestinal Stromal Tumors
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

Condition

• Advanced Gastrointestinal Stromal Tumors
• Metastatic Cancer

Intervention

• Drug: CGT9486 plus sunitinib
  Participants will receive both CGT9486 and sunitinib orally until study stopping rules are met.
• Drug: CGT9486
  Participants will receive CGT9486 until steady state then both CGT9486 and sunitinib orally until study stopping rules are met.
• 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
• Drug: Sunitinib
  Participants will receive sunitinib orally until study stopping rules are met.
  Other Name: sunitinib - Part 2

Study Arms

• Experimental: Part 1a
  CGT9486 plus sunitinib 37.5 mg QD
  Intervention: Drug: CGT9486 plus sunitinib
• Experimental: Part 2 - Experimental Group
  CGT9486 plus sunitinib 37.5 mg QD
  Intervention: Drug: CGT9486 plus sunitinib
• Active Comparator: Part 2 - Control Group
  sunitinib 37.5 mg QD
  Intervention: Drug: Sunitinib
• Experimental: Part 1b - DDI Cohort 1
  CGT9486 plus sunitinib 37.5 mg QD
  Intervention: Drug: CGT9486
• Experimental: Part 1b - DDI Cohort 2
  sunitinib 37.5 mg QD plus CGT9486
  Intervention: Drug: Sunitinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 16, 2022): 426
• Original Estimated Enrollment (submitted: January 14, 2022): 388
• Estimated Study Completion Date: September 2026
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Eligibility 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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Argentina, Australia, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Hong Kong, Hungary, Italy, Korea, Republic of, Mexico, Netherlands, Norway, Poland, Spain, Sweden, Taiwan, United Kingdom, United States

Administrative Information

• NCT Number: NCT05208047
• Other Study ID Numbers: CGT9486-21-301
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Cogent Biosciences, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Cogent Biosciences, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Jessica Sachs, MD; Cogent Biosciences

• PRS Account: Cogent Biosciences, Inc.
• Verification Date: April 2024