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

Florida Cancer Specialists - Lake Nona
Orlando 4167147, Florida 4155751 32827
Contact:
Elizabeth Griffith- Gilmore
904-380-2418
elizabeth.griffith@scri.com

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02144

Nebraska Cancer Specialists
Omaha 5074472, Nebraska 5073708 68130
Contact:
Ashley Servais Degenhardt
402-955-2691
aservais@nebraskacancer.com

Carolina BioOncology Institute
Huntersville 4472370, North Carolina 4482348 28078
Contact:
Ryan Allen
704-947-6599
info@carolinabioooncology.org

UH Cleveland Medical Center
Cleveland 5150529, Ohio 5165418 44106
Contact:
833-788-7425

Sarah Cannon Nashville
Nashville 4644585, Tennessee 4662168 37203
Contact:
Referral Coordinator
615.329.7274
asksarah@scresearch.net

NEXT Oncology
Austin 4671654, Texas 4736286 78229
Contact:
Recruitment Coordinator
737-610-5200
NXTAUS_Coordinators@nextoncology.com

MD Anderson Cancer Center
Houston 4699066, Texas 4736286 77030
Contact:
877-589-0209

START Center for Cancer Research
San Antonio 4726206, Texas 4736286 78229
Contact:
Isabel Jimenez
210-593-5265
isabel.jimenez@startresearch.com

START Center for Cancer Research
West Valley City 5784607, Utah 5549030 84119
Contact:
Marie Assay
801-907-4770
marie.asay@startresearch.com

NEXT Oncology
Fairfax 4758023, Virginia 6254928 22031
Contact:
Referral Coordinator
(703) 783-4518
NXTAUS_Coordinators@nextoncology.com

PanOncology Trials
San Juan 4568127, Puerto Rico 00935
Contact:
Study Coordinator
info@panoncologytrials.com

More Details

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.