A Phase 1/2 Trial of TER-2013 in Patients With Solid Tumors Harboring AKT/PI3K/PTEN Pathway Alterations

Purpose

This is a Phase 1/2, open-label, multicenter study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics and anti-tumor activity of TER-2013 in patients with advanced solid tumors harboring AKT/PI3K/PTEN pathway alterations.

Conditions

  • Breast Cancer
  • Endometrial Cancer
  • Ovarian Cancer
  • Lung Squamous Cell Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Esophageal Squamous Cell Carcinoma
  • Solid Tumor
  • Cervical Cancer

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Metastatic or locally advanced, unresectable disease - No available treatment with curative intent - Presence of lesions to be evaluated per RECIST v1.1: a. Dose Escalation: measurable or evaluable disease b. Cohort Expansion: measurable disease - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Adequate organ function - Advanced solid tumor malignancy harboring an eligible AKT/PI3K/PTEN pathway alteration detected by a sponsor approved test Key Inclusion Criteria for TER-2013 monotherapy arms: - Histologically confirmed diagnosis of: a. [For TER-2013 dose escalation]: solid tumor malignancy b. [For TER-2013 cohort expansion]: i. Cohort 1: ovarian cancer, cervical cancer, or squamous cell carcinoma of the head and neck, lung, or esophagus ii. Cohort 2: endometrial adenocarcinoma - Prior therapy: 1. [For TER-2013 dose escalation]: Received standard therapies appropriate for their tumor type and stage, unless contraindicated, intolerable, or patient refused 2. [For TER-2013 cohort expansion]: No more than 3 prior lines of treatment in the advanced setting Key Inclusion Criteria for TER-2013 and fulvestrant combination arms - Histologically confirmed diagnosis of: a. [For TER-2013 + fulvestrant dose escalation]: HR+/HER2- advanced unresectable or metastatic breast cancer b. [For TER-2013 + fulvestrant cohort expansion]: i. Received treatment with an AI containing regimen (single agent or in combination) ii. No more than 3 prior lines of treatment in the advanced unresectable or metastatic setting - Prior Therapy: a. [For TER-2013 + fulvestrant dose escalation]: Received treatment with an AI containing regimen (single agent or in combination) b. [For TER-2013 + fulvestrant cohort expansion]: i. Received treatment with an AI containing regimen (single agent or in combination) ii. No more than 3 prior lines of treatment in the advanced unresectable or metastatic setting

Exclusion Criteria

  • Known EGFR, KRAS, NRAS, HRAS, or BRAF oncogenic-driver co-mutation with PI3K/AKT/PTEN alteration - Clinically significant abnormalities of glucose metabolism - Active brain metastases or carcinomatous meningitis. - History of significant hemoptysis or hemorrhage within 4 weeks prior to first dose of study drug - Malabsorption syndrome, nausea and vomiting uncontrolled by medication, or disease significantly affecting gastrointestinal function likely to interfere with the delivery, absorption, or metabolism of TER-2013 - Prior therapy: 1. [For TER-2013 monotherapy escalation]: AKT inhibitor 2. [For TER-2013 monotherapy expansion]: AKT/PI3K/PTEN pathway inhibitor 3. [For TER-2013 + fulvestrant combination expansion]: AKT/PI3K/PTEN pathway inhibitor, fulvestrant and other SERDs, mTOR inhibitor; some PIK3CA-altered cohorts allow prior PI3K inhibitor. Other protocol-defined Inclusion/Exclusion Criteria apply

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Monotherapy Dose Escalation
  • Drug: TER-2013
    Oral Capsules
Experimental
Combination Therapy Dose Escalation 		Dose Escalation of TER-2013 with recommended dose of fulvestrant
  • Drug: TER-2013
    Oral Capsules
  • Drug: Fulvestrant injection
    Fulvestrant 500 mg Intramuscular Injection
Experimental
Monotherapy Dose Expansion
  • Drug: TER-2013
    Oral Capsules
Experimental
Combination Therapy Dose Expansion 		Dose Expansion of TER-2013 with recommended dose of fulvestrant
  • Drug: TER-2013
    Oral Capsules
  • Drug: Fulvestrant injection
    Fulvestrant 500 mg Intramuscular Injection

Recruiting Locations

Washington University in St. Louis and nearby locations

Washington Univ. School of Medicine
St Louis, Missouri 63110
Contact:
Study Coordinator
800-600-3606
enix@wustl.edu

More Details

NCT ID
NCT07109726
Status
Recruiting
Sponsor
Terremoto Biosciences Inc.

Study Contact

Terremoto Biosciences, Inc. Clinical Trials Central Contact
888-682-1551
clinicaltrials@terremotobio.com

Detailed Description

This is a first-in-human clinical trial that will evaluate the safety, tolerability, and pharmacokinetics (PK) of TER-2013 as a monotherapy and in combination with fulvestrant and to determine the maximum tolerated/administered dose and preliminary clinical activity. The study consists of two parts: Part 1-Dose Escalation and Part 2 -Dose Expansion.