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

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.

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.

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