Protocol No.UW25018
FOG-001-101
Principal InvestigatorKratz, Jeremy
PhaseI/II
Age GroupAdult
ClinicalTrials.GovNCT05919264 (Click to jump to clinicaltrials.gov)
Management Group(s) Early Phase

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

Description
The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic cancer.

Objective
Primary Objectives

Part 1
-To assess the safety and tolerability of FOG-001 alone or in combination across a range of dose levels and dosing schedules in participants with locally advanced or metastatic solid tumors to determine the MTD or maximum feasible dose.

Part 2
-To further characterize the safety and tolerability of FOG-001 alone or in combination at the RP2D
-To evaluate the preliminary antitumor activity of FOG-001 alone or in combination in advanced cancer participants with centrally-confirmed WPAM

Secondary Objectives

Part 1
-To characterize the PK profile of FOG-001 and associated metabolites
-To select the preliminary RP2D and dosing schedule of FOG-001 for participants with advanced or metastatic solid tumors
-Evaluation of FOG-001 pharmacodynamic activity in tumors (Part 1b only)
-To evaluate the preliminary antitumor activity of FOG-001 alone or in combination in advanced cancer participants by WPAM status and by tumor type

Part 2
-To evaluate the preliminary antitumor activity of FOG-001 alone or in combination in advanced cancer participants, with centrally-confirmed WPAM
-To evaluate the preliminary antitumor activity of FOG-001 alone or in combination in advanced cancer participants, with WPAM based on local testing
-To evaluate the PK profile of FOG-001 and associated metabolites

Treatment 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).

Key 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 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

Applicable Disease Sites
Anal; Any Site; Bladder; Brain/Central Nervous System; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Hematologic cancers, other; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital