Breast Cancer, Endometrial Cancer, Ovarian Cancer, Lung Squamous Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Esophageal Squamous Cell Carcinoma, Solid Tumor, Cervical Cancer
Conditions
Keywords
AKT/PI3K/PTEN Alterations, Breast Cancer, Advanced Solid Tumors, HR+/HER2-
Brief summary
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.
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.
Interventions
DRUGTER-2013
Oral Capsules
Fulvestrant 500 mg Intramuscular Injection
Sponsors
Terremoto Biosciences Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 Key
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Patients who Experience Dose-Limiting Toxicity | 28 Days |
| Number of patients who experience a treatment-related adverse event | Up to 2 years |
| Objective Response Rate as assessed by RECIST v1.1 | Up to 2 years |
| Duration of Response as assessed by RECIST v1.1 | Up to 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Area under the plasma concentration-time curve for a dosing interval (AUCτ) of TER-2013 | Up to 2 years |
| Maximum concentration (Cmax) of TER-2013 | Up to 2 years |
| Time to maximum concentration (Tmax) of TER-2013 | Up to 2 years |
| Terminal elimination half-life (T1/2) of TER-2013 | Up to 2 years |
| Changes of pharmacodynamic markers of TER-2013 in tissue and/or blood as assessed by pAKT | Up to 2 years |
| Changes of pharmacodynamic markers of TER-2013 in tissue and/or blood as assessed by pPRAS40 | Up to 2 years |
Countries
Puerto Rico, United States
Contacts
CONTACTTerremoto Biosciences, Inc. Clinical Trials Central Contact
Outcome results
None listed