Overview
The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic cancer.
Description
This first-in-human, Phase 1/2, multicenter, open-label, non-randomized dose escalation and expansion study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of FOG-001 in participants with locally advanced or metastatic solid tumors. FOG-001 is a first-in-class direct inhibitor of Beta-catenin, which functions by blocking its interaction with the T-cell factor (TCF) family of transcription factors.
Eligibility
Inclusion Criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate organ and marrow function.
Additional Inclusion Criteria for Dose Escalation Cohorts (Part 1a):
- Diagnosis of treatment-refractory advanced/metastatic solid tumor that is non-MSI-H or non-dMMR colorectal cancer (CRC) or any other solid tumor with documented WNT- pathway activating mutations (WPAMs).
Additional Inclusion Criteria for Dose Escalation Cohorts (Part 1b):
- Diagnosis of treatment-refractory advanced/metastatic non-MSI-H or non-dMMR CRC.
- At least one lesion that is suitable for a core needle biopsy.
Additional Inclusion Criteria for Dose Expansion Cohort (Cohort 2a): Colorectal Cancer (CRC) Cohort - Diagnosis of treatment-refractory advanced/metastatic non-MSI-H or non-dMMR CRC. Additional Inclusion Criteria for Dose Expansion Cohort (Cohort 2b): Non-small Cell Lung Cancer (NSCLC) Cohort - Diagnosis of treatment-refractory advanced/metastatic NSCLC with documented WPAMs in adenomatous polyposis coli (APC) or Beta-catenin. Additional Inclusion Criteria for Dose Expansion Cohort (Cohort 2c): Gastric/Gastroesophageal junction (GEJ) Cohort - Diagnosis of treatment-refractory advanced/metastatic gastric/GEJ cancer with documented WPAMs in APC or Beta-catenin. Additional Inclusion Criteria for Dose Expansion Cohort (Cohort 2d): Tumor Agnostic Cohort - Diagnosis of treatment-refractory advanced/metastatic solid tumor with documented WPAMs. Exclusion Criteria: - Known history of bone metastasis. - Evidence of vertebral compression fracture or non-traumatic bone fracture within the past 12 months and who are not receiving antiresorptive therapy. - Osteoporosis, which is defined as a T-score of <-2.5 at the lumbar spine (L1 - L4), left (or right) femoral neck or left (or right) total hip as determined by DXA scan, or a FRAX 10-year probability of hip fracture ≥3% or a 10-year probability of major osteoporosis-related fracture ≥20%, based on the US-adapted WHO algorithm for postmenopausal women and men ≥50 years of age. - Inflammatory bowel disease (i.e., ulcerative colitis or Crohn's disease) that is recently active or requires therapy currently. - Unstable/inadequate cardiac function. - Has known meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases. - Pregnant, lactating, or planning to become pregnant.