A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors

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.

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.
• Osteoporosis, which is defined as a T-score of <-2.0 at the lumbar spine (L1 - L4), left (or right) femoral neck, and left (or right) total hip as determined by DXA scan.
• 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.