FOG-001 in Locally Advanced or Metastatic Solid Tumors

Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05919264
• Other study ID #: FOG-001-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 19, 2023
• Est. completion date: August 31, 2027

Study information

• Verified date: June 2024
• Source: Fog Pharmaceuticals, Inc.
• Contact: Clinical Trial Inquiries
• Phone: (857) 259-6305
• Email: clinicaltrials[@]fogpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 245
• Est. completion date: August 31, 2027
• Est. primary completion date: April 1, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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):

• 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 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, or a FRAX 10-year probability of hip fracture =3% or a 10-year probability of major osteoporosis-related fracture =20%, based on the US-adapted WHO algorithm for postmenopausal women and men =50 years of age.

• 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.

Related Conditions & MeSH terms

• Adenomatous Polyposis Coli
• Cancer
• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Gastric Cancer
• Gastroesophageal-junction Cancer
• Locally Advanced Solid Tumor
• Lung Neoplasms
• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Non-small Cell Carcinoma
• Non-Small Cell Carcinoma of Lung, TNM Stage 4
• Non-small Cell Lung Cancer
• Non-small Cell Lung Cancer Metastatic
• Non-small Cell Lung Cancer Stage IIIB
• Solid Tumor
• Stomach Neoplasms

Intervention

Drug:
• FOG-001
FOG-001 will be administered IV at assigned doses in continuous cycles of 21 or 28 days
• FOG-001
FOG-001 will be administered IV once weekly at the preliminary RP2D dose in continuous cycles of 21 or 28 days

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Oregon Health and Science University	Portland	Oregon
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	South Texas Accelerated Research Therapeutics, LLC	San Antonio	Texas
United States	Honor Health	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Fog Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0	Number and severity of treatment emergent adverse events as assessed by CTCAE v5.0	Through study completion, an average of 4 months
Primary	During dose escalation characterize dose-limiting toxicities (DLTs)	Incidence of DLTs	1 treatment cycle (21 or 28 days)
Primary	During dose expansion describe the Overall Response Rate using RECIST v1.1	The rate of objective responses (Partial & Complete) using RECIST v1.1	Every 56 or 63 days until study completion, approximately 4 months on average
Secondary	Plasma concentration (Cmax) of FOG-001		During first 2 cycles (42 or 56 days)
Secondary	Time to achieve Cmax (Tmax) of FOG-001 in plasma		During first 2 cycles (42 or 56 days)
Secondary	Area under the plasma concentration-time curve (AUC) of FOG-001		During first 2 cycles (42 or 56 days)
Secondary	Clearance (CL) of FOG-001 from the plasma		During first 2 cycles (42 or 56 days)
Secondary	Terminal half-life (t1/2) of FOG-001 in plasma		During first 2 cycles (42 or 56 days)
Secondary	During dose escalation select the preliminary recommended Phase 2 dose and dosing schedule of study drug	Rate of Dose Limiting Toxicities (DLTs) across dose levels	During Cycle 1 (21 or 28 days)
Secondary	During dose escalation Part 1b to evaluate the pharmacodynamic activity in tumors	Change in tumor Myc expression (on-study compared to baseline)	During first 2 cycles (42 or 56 days)
Secondary	During dose escalation and expansion to describe Best Overall Response Rate using RECIST v1.1	Best response to treatment using RECIST v1.1	Every 56 or 63 days until study completion, approximately 4 months on average
Secondary	During dose escalation and expansion to describe Duration of Response using RECIST v1.1	Time from initial objective response (partial response or complete response) to disease progression	Every 56 or 63 days until study completion, approximately 4 months on average
Secondary	During dose expansion describe Progression Free Survival	Progression Free Survival (PFS) using RECIST v1.1	From date of randomization until the date of first disease progression, an average of 4 months