FOG-001 in Locally Advanced or Metastatic Solid Tumors

Prior treatment

• Evidence of vertebral compression fracture or non-traumatic bone fracture within the past 12 months and who are not receiving antiresorptive therapy.
• Complete colectomy within 6 months of the first dose of study drug administration.

Other illness

• Known history of bone metastasis. Bone metastasis are allowed for patients with mCRPC. For participants with FAP, osteomas are allowed.
• Uncontrolled inflammatory bowel disease (i.e., ulcerative colitis or Crohn's disease)
• Unstable/inadequate cardiac function.

Other

• 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.
• Has known meningeal carcinomatosis, leptomeningeal carcinomatosis, spinal cord compression, or symptomatic or unstable brain metastases.
• Pregnant, lactating, or planning to become pregnant.

• 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 and Part 1g):
• 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 Escalation and Dose Expansion Cohorts (Part 1c and Part 2c):
• Histologically, cytologically, or radiographically confirmed HCC with a documented WPAM (by local ctDNA or tumor NGS testing) in APC or CTNNB1
  • Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1d, Part 1h, and Part 2d):
• Desmoid tumor (aggressive fibromatosis)
  • Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1f-1 and Part 2f-1) FOG-001 + FOLFOX + Bevacizumab:
• Diagnosis of locally advanced or metastatic non-MSI-H or non-dMMR CRC
• Participants with tumors known to be negative for APC LoF mutations or CTNNB1 GoF mutations (per NGS tests) are not eligible.
• One dose of mFOLFOX6 with or without bevacizumab in the unresectable or metastatic setting prior to enrollment is allowed.
  • Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1f-2 and Part 2f-2): FOG-001 + Nivolumab
• Non-MSI-H or non-dMMR (by local testing) CRC with or without liver metastases.
• MSI-H CRC or solid tumors that are WPAM and resistant to a-PD-1/PD-L1
• Participants with tumors known to be negative for APC LoF mutations or CTNNB1 GoF mutations (per NGS tests) are not eligible
  • Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1f-3 and Part 2f-3): FOG-001 + Trifluridine/Tipiracil + Bevacizumab
• Diagnosis of locally advanced or metastatic non-MSI-H or non-dMMR (by local testing) CRC
• Participants with tumors known to be negative for APC LoF mutations or CTNNB1 GoF mutations (per NGS tests) are not eligible.
  • Monotherapy Dose Optimization (Part 1i): FAP
• Diagnosis of phenotypic classical FAP with a documented APC mutation
• Post-colectomy \>6 months prior to first dose of study drug administration with measurable duodenal polyp burden
  • Additional Inclusion Criteria for Dose Expansion Cohort (Part 2a):
• Diagnosis of locally advanced or metastatic non-MSI-H or non-dMMR (by local testing) CRC
  • Additional Inclusion Criteria for Dose Expansion Cohort (Part 2b):
• Diagnosis of advanced or metastatic solid tumors with a documented WPAM (by local testing) or equivalent evidence