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

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.

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/Exclusion Criteria apply