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

NCT07383506 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CGT6297-25-101
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Endometrial Cancer; HR Positive/HER-2 Negative Breast Cancer; HER2-low Breast Cancer; PIK3CA Mutations; Advanced Solid Tumors, Adult

Keywords

HER2; PI3K; Mutant-Selective Inhibitor; Advanced solid tumors; PIK3CA Mutations; PIK3CA SNVs; Endometrial Cancer; Breast Cancer; 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; HER2-low Breast Cancer; Phase 1a/1b

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Incidence and grade of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Phase 1b]

  Approximately 12 months

• Pharmacokinetics (Part 1a)

  Approximately 28 days

• Pharmacokinetics (Part 1a)

  Approximately 28 days

• Pharmacokinetics (Part 1a)

  Approximately 28 days

• Pharmacokinetics (Part 1a)

  Approximately 28 days

Study Arms (2)

Dose Escalation

EXPERIMENTAL

Part 1a: Dose Escalation of Multiple doses of CGT6297 for oral administration

Drug: CGT6297

Signal Seeking

EXPERIMENTAL

Phase 1b: Participants will receive CGT6297 at a dose level selected based on data from Phase 1a

Drug: CGT6297

Interventions

CGT6297 DRUG

CGT6297 Daily Oral Administration

Dose Escalation; Signal Seeking

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed advanced solid tumor harboring oncogenic PIK3CA mutations in blood and/or tumor:
• Phase 1b Cohort 1, participants must have PIK3CA endometrial cancer
• 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)
• 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
• Meet prior treatment requirement of:
• Phase 1a: previously treated with and refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
• Phase 1b: previously treated with or considered not appropriate for SOC first-line treatment for their condition
• Have at least one measurable lesion according to RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
• Have clinically acceptable local laboratory screening results (clinical chemistry and hematology) within certain limits
• 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.
• Have an ejection fraction ≥50%

You may not qualify if:

• Received small molecule chemotherapy or anticancer therapies or radiotherapy within certain timeframes before first dose of study drug.
• Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study drug
• Treatment with radiotherapy ≤2 weeks before the first dose of study drug.
• Clinically significant cardiac disease
• 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)
• 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)
• 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

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (2)

NEXT Austin

Austin, Texas, 78758, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Endometrial Neoplasms; Breast Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Cogent Biosciences, Inc

CONTACT

6179455576; trialinfo@cogentbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1, Part A evaluating multiple ascending doses Phase 1b, evaluation of Part A selected doses in 3 cohorts defined by tumor type including a randomized dose optimization design (Part B)

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 3, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): August 1, 2029
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)