Clinical Trial Finder

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 and Part 1e):

• - 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):

• - Diagnosis of HCC with a documented WPAM (by local testing) in APC or CTNNB1.

HCC that is radiographically confirmed without tissue biopsy may be enrolled with a documented CTNNB1 mutation (e.g., by ctDNA). Additional Inclusion Criteria for Dose Escalation and Dose Expansion Cohorts (Part 1d and Part 2d):

• - Desmoid tumor (aggressive fibromatosis) with a documented WPAM (by local testing) in APC or CTNNB1.

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.

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.

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.

Exclusion Criteria:

• - Known history of bone metastasis.

Bone metastasis are allowed for patients with mCRPC.

• - 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.

• - 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.

This is a FIH, Phase 1/2, multicenter, open-label, non-randomized, dose escalation and dose expansion study to evaluate the safety, tolerability, PK, pharmacodynamics, and antitumor activity of FOG-001 as monotherapy and in combination with other anticancer agents in participants with advanced or metastatic solid tumors likely or known to have a Wnt pathway activating mutation (WPAM).

Arms

Experimental: Part 1a

Solid Tumors with any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (CRC), irrespective of WPAM status

Experimental: Part 1b

MSS CRC (known WPAM negative participants are not eligible)

Experimental: Part 1c

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

Experimental: Part 1d

Desmoid Tumors (documented WPAM in APC or CTNNB1 required)

Experimental: Part 1e-1

Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status

Experimental: Part 1e-2

Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status

Experimental: Part 1f-1

MSS CRC (known WPAM negative participants are not eligible)

Experimental: Part 1f-2

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

Experimental: Part 1f-3

MSS CRC (known WPAM negative participants are not eligible)

Experimental: Part 2a

MSS CRC, irrespective of WPAM status

Experimental: Part 2b

Solid Tumors with documented WPAM

Experimental: Part 2c

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

Experimental: Part 2d

Desmoid Tumors (documented WPAM in APC or CTNNB1 required)

Experimental: Part 2e

Metastatic Castration-Resistant Prostate Cancer (documented WPAM in APC or CTNNB1 required)

Experimental: Part 2f-1

MSS CRC (known WPAM negative participants are not eligible)

Experimental: Part 2f-2

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

Experimental: Part 2f-3

MSS CRC (known WPAM negative participants are not eligible)

Interventions

Drug: - FOG-001

FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days

Drug: - mFOLFOX-6

mFOLFOX-6 will be administered per the prescribing information in combination with FOG-001

Drug: - Nivolumab

Nivolumab will be administered per the prescribing information in combination with FOG-001

Drug: - Trifluridine/tipiracil

Trifluridine/tipiracil will be administered per the prescribing information in combination with FOG-001

Drug: - Bevacizumab

Bevacizumab will be administered per the prescribing information in combination with FOG-001