FOG-001 in Locally Advanced or Metastatic Solid Tumors

Sponsor

Fog Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05919264

Collaborator

(none)

208

Enrollment

Location

Arms

51.4

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Cancer Colorectal Cancer Solid Tumor Locally Advanced Solid Tumor Metastatic Cancer Gastric Cancer Non-small Cell Lung Cancer Non-small Cell Carcinoma Non-small Cell Lung Cancer Metastatic Non-small Cell Lung Cancer Stage IIIB Non-Small Cell Carcinoma of Lung, TNM Stage 4 Gastroesophageal-junction Cancer	Drug: FOG-001 Drug: FOG-001	Phase 1/Phase 2

Detailed Description

This first-in-human, Phase 1/2, multicenter, open-label, non-randomized dose escalation and expansion study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, 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 β-catenin, which functions by blocking its interaction with the T-cell factor (TCF) family of transcription factors.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

208 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 19, 2023

Anticipated Primary Completion Date :

Apr 1, 2027

Anticipated Study Completion Date :

Aug 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1a Solid Tumors with Any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (Irrespective of WPAM Status)	Drug: FOG-001 FOG-001 will be administered IV once weekly at assigned doses in continuous cycles of 28 days
Experimental: Part 1b Microsatellite Stable Colorectal Cancer	Drug: FOG-001 FOG-001 will be administered IV once weekly at assigned doses in continuous cycles of 28 days
Experimental: Cohort 2a Microsatellite Stable Colorectal Cancer	Drug: FOG-001 FOG-001 will be administered IV once weekly at the RP2D dose in continuous cycles of 28 days
Experimental: Cohort 2b Non-Small Cell Lung Cancer with a WNT-Pathway Activating Mutation (WPAM) in APC or Beta-Catenin	Drug: FOG-001 FOG-001 will be administered IV once weekly at the RP2D dose in continuous cycles of 28 days
Experimental: Cohort 2c Gastric Cancer/Gastroesophageal Junction Carcinoma (GEJ) with a WNT-Pathway Activating Mutation (WPAM) in APC or Beta-Catenin	Drug: FOG-001 FOG-001 will be administered IV once weekly at the RP2D dose in continuous cycles of 28 days
Experimental: Cohort 2d Solid Tumors with Any WNT-Pathway Activating Mutation (WPAM)	Drug: FOG-001 FOG-001 will be administered IV once weekly at the RP2D dose in continuous cycles of 28 days

Outcome Measures

Primary Outcome Measures

During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0 [Through study completion, an average of 4 months]
Number and severity of treatment emergent adverse events as assessed by CTCAE v5.0
During dose escalation characterize dose-limiting toxicities (DLTs) [1 treatment cycle (28 days)]
Incidence of DLTs
During dose expansion describe the Overall Response Rate using RECIST v1.1 [Every 56 days until study completion, approximately 4 months on average]
The rate of objective responses (Partial & Complete) using RECIST v1.1

Secondary Outcome Measures

Pharmacokinetic profile [During first 2 cycle (56 days)]
Study drug exposure over time
During dose escalation select the recommended Phase 2 dose and dosing schedule of study drug [During Cycle 1 (28 days)]
Rate of Dose Limiting Toxicities (DLTs) across dose levels
During dose escalation Part 1b to evaluate the pharmacodynamic activity in tumors [During first 2 cycles (56 days)]
Change in tumor Myc expression (on-study compared to baseline)
During dose escalation and expansion to describe Best Overall Response Rate using RECIST v1.1 [Every 56 days until study completion, approximately 4 months on average]
Best response to treatment using RECIST v1.1
During dose escalation and expansion to describe Duration of Response using RECIST v1.1 [Every 56 days until study completion, approximately 4 months on average]
Time from initial objective response (PR or CR) to disease progression
During dose expansion describe Progression Free Survival [From date of randomization until the date of first disease progression, an average of 4 months.]
Progression Free Survival (PFS) using RECIST v1.1

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 either non-MSI-H or non-dMMR CRC or any other solid tumor with documented WPAM.

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 core needle biopsy.

Additional Inclusion Criteria for Dose Expansion Cohort (Cohort 2a): CRC Cohort

Diagnosis of treatment refractory advanced/metastatic non-MSI-H or non-dMMR CRC

Additional Inclusion Criteria for Dose Expansion Cohort (Cohort 2b): NSCLC Cohort

Diagnosis of treatment refractory advanced/metastatic NSCLC with a documented WPAM mutation in APC or beta-catenin.

Additional Inclusion Criteria for Dose Expansion Cohort (Cohort 2c): Gastric/GEJ Cohort

Diagnosis of treatment refractory advanced/metastatic gastric/GEJ cancer with a documented WPAM mutation 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 a documented WPAM mutation.

Exclusion Criteria:

Known history of bone metastasis.
Evidence of vertebral compression fracture or non-traumatic bone fracture within the past 12 months.
Osteoporosis 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 is currently requiring therapy.
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.