FOG-001: FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
mFOLFOX-6: mFOLFOX-6 will be administered per the prescribing information in combination with FOG-001
Nivolumab: Nivolumab will be administered per the prescribing information in combination with FOG-001
Trifluridine/tipiracil: Trifluridine/tipiracil will be administered per the prescribing information in combination with FOG-001
Bevacizumab: Bevacizumab will be administered per the prescribing information in combination with FOG-001
FOG-001: FOG-001 will be administered subcutaneous at assigned doses in continuous cycles of 28 days
Study summary
The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic solid tumors or in participants with familial adenomatous polyposis (FAP).
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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 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
Exclusion Criteria:
* Known history of bone metastasis. Bone metastasis are allowed for patients with mCRPC. For participants with FAP, osteomas are allowed.
* 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.
* Uncontrolled inflammatory bowel disease (i.e., ulcerative colitis or Crohn's disease)
* 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.
* Complete colectomy within 6 months of the first dose of study drug administration.
Primary outcome measure(s)
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 10 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 63 days until study completion, approximately 10 months on average The rate of objective responses (Partial \& Complete) using RECIST v1.1
During dose expansion describe the Disease Control Rate using RECIST v1.1 (Part 2a only) — 4 months The rate of objective responses (Stable, Partial, \& Complete) using RECIST v1.1
During dose expansion describe the PSA30 response rate for participants with prostate cancer — Baseline, weekly during the first 2 cycles (56 days), bi-weekly during the Cycle 3 (28 days), and then monthly (up to approximately 7 months) The response to treatment as a 30% or greater reduction in PSA levels from baseline
Trial sites (33)
Facility
City
Region
Status
Mayo Clinic
Phoenix
Arizona
Recruiting
Honor Health
Scottsdale
Arizona
Recruiting
Arizona Cancer Center at University of Arizona
Tucson
Arizona
Recruiting
University of California, Los Angeles (UCLA)
Los Angeles
California
Recruiting
Stanford Cancer Institute, Stanford University
Palo Alto
California
Recruiting
University of California San Francisco, Helen Diller Family Comprehensive Cancer Center
San Francisco
California
Recruiting
Sarcoma Oncology Center
Santa Monica
California
Recruiting
University of Colorado
Aurora
Colorado
Recruiting
Yale University School of Medicine
New Haven
Connecticut
Recruiting
Johns Hopkins University, Sibley Memorial Hospital
Washington D.C.
District of Columbia
Recruiting
Mayo Clinic
Jacksonville
Florida
Recruiting
Florida Cancer Specialists
Lake Mary
Florida
Terminated
Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer Center
Baltimore
Maryland
Recruiting
Massachusetts General Hospital
Boston
Massachusetts
Recruiting
Dana Farber Cancer Institute
Boston
Massachusetts
Recruiting
M Health Fairview University of Minnesota Medical Center
Minneapolis
Minnesota
Recruiting
Mayo Clinic
Rochester
Minnesota
Recruiting
Washington University School of Medicine
St Louis
Missouri
Recruiting
Memorial Sloan Kettering Cancer Center
New York
New York
Recruiting
Duke University
Durham
North Carolina
Recruiting
University Hospitals Cleveland Medical Center, Seidman Cancer Center
Cleveland
Ohio
Recruiting
Cleveland Clinic
Cleveland
Ohio
Recruiting
Oregon Health and Science University
Portland
Oregon
Recruiting
University of Pennsylvania, Perelman School of Medicine
Philadelphia
Pennsylvania
Recruiting
University of Pittsburgh Medical Center, Hillman Cancer Center
Pittsburgh
Pennsylvania
Recruiting
Sarah Cannon Research Institute
Nashville
Tennessee
Recruiting
Vanderbilt Ingram Cancer Center
Nashville
Tennessee
Recruiting
The University of Texas MD Anderson Cancer Center
Houston
Texas
Recruiting
South Texas Accelerated Research Therapeutics, LLC
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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