A Study of Mutant Selective-Inhibitor (CGT6297), in Patients With Advanced Solid Tumors

A Study of a Mutant-Selective Inhibitor, CGT6297, in Patients With Advanced Solid Tumors Harboring PIK3CA Mutations

This is a Phase 1, two-part, open-label, nonrandomized, dose-escalation and signal-seeking study of CGT6297, evaluating the safety, tolerability, PK, pharmacodynamic (what the drug does to the body), and antitumor activity of CGT6297 in adult participants with advanced solid tumors harboring PIK3CA mutations

Study Overview

• Status: Not yet recruiting
• Conditions: Endometrial Cancer; HER2-low Breast Cancer; HR Positive/HER-2 Negative Breast Cancer; PIK3CA Mutations; Advanced Solid Tumors, Adult
• Intervention / Treatment: Drug: CGT6297

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cogent Biosciences, Inc; Phone Number: 6179455576; Email: trialinfo@cogentbio.com

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78758
      • NEXT Austin
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed advanced solid tumor harboring oncogenic PIK3CA mutations in blood and/or tumor:

   1. Phase 1b Cohort 1, participants must have PIK3CA endometrial cancer
   2. Phase 1b Cohort 2, participants must have HR-positive/HER2-negative or HER2-low breast cancer (immunohistochemistry [IHC] and in-situ hybridization results must meet ASCO-College of American Pathology guidelines for breast cancer or criteria)
   3. Phase 1b Cohort 3 will allow all solid tumors that do not meet criteria for Phase 1b Cohorts 1 or 2, including head and neck cancers, other gynecological cancers, colorectal cancers harboring PIK3CA mutations

2. Meet prior treatment requirement of:

   1. Phase 1a: previously treated with and refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
   2. Phase 1b: previously treated with or considered not appropriate for SOC first-line treatment for their condition
3. Have at least one measurable lesion according to RECIST v1.1.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
5. Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
6. Resolution of acute toxicities from prior anticancer therapy to ≤Grade 1 (or baseline), including resolution of clinically significant laboratory abnormalities (other than parameters specified in screening testing as outlined below), as determined by the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCICTCAE) v5.0.
7. Have an ejection fraction ≥50%

Exclusion Criteria:

1. Received small molecule chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
2. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
3. Treatment with radiotherapy ≤2 weeks before the first dose of study drug.
4. Clinically significant cardiac disease
5. Ongoing or planned long-term (≥4 consecutive weeks) treatment with glucocorticoid steroids at greater than physiologic dosing (defined as equivalent to >20 mg/day prednisone)
6. Diagnosis of diabetes mellitus type 1 or uncontrolled diabetes mellitus type 2 (defined as fasting glucose ≥140 mg/dL and HbA1c ≥7.0%; antihyperglycemic medical management permitted with the exception of insulin)
7. Previous molecular testing (NGS or PCR) showed tumor with the following mutations: mutations/deletions in PTEN or activating mutations in AKT, HRAS/KRAS/NRAS, EGFR, and BRAF

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Part 1a: Dose Escalation of Multiple doses of CGT6297 for oral administration	Drug: CGT6297; CGT6297 Daily Oral Administration
Experimental: Signal Seeking; Phase 1b: Participants will receive CGT6297 at a dose level selected based on data from Phase 1a	Drug: CGT6297; CGT6297 Daily Oral Administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Phase 1a]	Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) and AEs leading to dose modifications and dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD) or the maximum evaluated dose (MED) of CGT6297 in participants with advanced solid tumors harboring PIK3CA mutations	Approximately 12 months
Overall Response Rate [Phase 1b]	Overall Response Rate (ORR), as determined by CR + PR based on Investigator assessment using RECIST v1.1	Approximately 8 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Phase 1b]	Incidence and grade of Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs leading to dose modification; Changes from baseline in key laboratory results and electrocardiogram (ECG) parameters	Approximately 12 months
Pharmacokinetics (Part 1a)	Area under the concentration-time curve (AUC) in participants with advanced solid tumors harboring PI3K mutations	Approximately 28 days
Pharmacokinetics (Part 1a)	Maximum observed concentration (Cmax) in participants with advanced solid tumors harboring PI3K mutations	Approximately 28 days
Pharmacokinetics (Part 1a)	Observed concentration at predose (Ctrough) in participants with advanced solid tumors harboring PI3K mutations	Approximately 28 days
Pharmacokinetics (Part 1a)	Time to maximum concentration (Tmax) in participants with advanced solid tumors harboring PI3K mutations	Approximately 28 days
Disease Response (Part 1b)	Objective response rate (ORR), determined by confirmed (CR) + (PR) based on Investigator assessment using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	Approximately 8 months
Disease Response (Part 1b)	Disease control rate (DCR), as determined by confirmed CR + PR + stable disease (SD) based on Investigator assessment using RECIST v1.1	Approximately 28 days

Collaborators and Investigators

• Sponsor: Cogent Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): August 1, 2029

Study Registration Dates

• First Submitted: January 26, 2026
• First Submitted That Met QC Criteria: January 26, 2026
• First Posted (Actual): February 3, 2026

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 25, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; HER2; Endometrial Cancer; PI3K; Advanced solid tumors; PIK3CA Mutations; HER2-low Breast Cancer; Phase 1a/1b; Mutant-Selective Inhibitor; PIK3CA SNVs; HR+/HER2 Negative breast cancer; HR+/HER2 (-) breast cancer; HR+/HER2 low breast cancer; PI3KCA Genetic Alterations; PI3KCA Point Mutations; PI3KCA Gene Short Variants; PI3KCA active alteration
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Uterine Neoplasms; Skin and Connective Tissue Diseases; Breast Neoplasms; Endometrial Neoplasms
• Other Study ID Numbers: CGT6297-25-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No