Overview
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.
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.
Eligibility
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:
- 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:
- \[For TER-2013 dose escalation\]: 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:
- \[For TER-2013 dose escalation\]: Received standard therapies appropriate for their tumor type and stage, unless contraindicated, intolerable, or patient refused
- \[For TER-2013 cohort expansion\]: 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:
- \[For TER-2013 + fulvestrant dose escalation\]: 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:
- \[For TER-2013 + fulvestrant dose escalation\]: 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:
- \[For TER-2013 monotherapy escalation\]: AKT inhibitor
- \[For TER-2013 monotherapy expansion\]: AKT/PI3K/PTEN pathway inhibitor
- \[For TER-2013 + fulvestrant combination expansion\]: 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