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FOG-001 in Locally Advanced or Metastatic Solid Tumors
NCT05919264 · Parabilis Medicines, Inc.
In plain English
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Official title
A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors
About this study
This is a FIH, Phase 1/2, multicenter, open-label, non-randomized, dose escalation, dose expansion, and multiple subcutaneous dose 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).
Eligibility criteria
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.
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.
* 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.
Study design
Enrollment target: 595 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-05-23
Estimated completion: 2027-08-31
Last updated: 2026-04-09
Interventions
Drug: FOG-001Drug: mFOLFOX-6Drug: NivolumabDrug: Trifluridine/tipiracilDrug: BevacizumabDrug: FOG-001
Primary outcomes
- • 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)
- • During dose escalation characterize dose-limiting toxicities (DLTs) (1 treatment cycle (28 days))
- • During dose expansion describe the Overall Response Rate using RECIST v1.1 (Every 63 days until study completion, approximately 10 months on average)
Sponsor
Parabilis Medicines, Inc. · industry
Contacts & investigators
ContactClinical Trial Inquiries · contact · clinicaltrials@parabilismed.com · (857) 259-6305
InvestigatorJorge Ramos, DO · study_chair, Parabilis Medicines, Inc.
All locations (24)
Honor HealthRecruiting
Scottsdale, Arizona, United States
Arizona Cancer Center at University of ArizonaRecruiting
Tucson, Arizona, United States
Stanford Cancer Institute, Stanford UniversityRecruiting
Palo Alto, California, United States
University of California San Francisco, Helen Diller Family Comprehensive Cancer CenterRecruiting
San Francisco, California, United States
Sarcoma Oncology CenterRecruiting
Santa Monica, California, United States
Yale University School of MedicineRecruiting
New Haven, Connecticut, United States
Johns Hopkins University, Sibley Memorial HospitalRecruiting
Washington D.C., District of Columbia, United States
Florida Cancer SpecialistsTerminated
Lake Mary, Florida, United States
Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer CenterRecruiting
Baltimore, Maryland, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Dana Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
M Health Fairview University of Minnesota Medical CenterRecruiting
Minneapolis, Minnesota, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
University Hospitals Cleveland Medical Center, Seidman Cancer CenterRecruiting
Cleveland, Ohio, United States
Cleveland ClinicRecruiting
Cleveland, Ohio, United States
Oregon Health and Science UniversityRecruiting
Portland, Oregon, United States
University of Pittsburgh Medical Center, Hillman Cancer CenterRecruiting
Pittsburgh, Pennsylvania, United States
Sarah Cannon Research InstituteRecruiting
Nashville, Tennessee, United States
Vanderbilt Ingram Cancer CenterRecruiting
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
South Texas Accelerated Research Therapeutics, LLCRecruiting
San Antonio, Texas, United States
University of VirginiaRecruiting
Charlottesville, Virginia, United States
University of Wisconsin, Carbone Cancer CenterRecruiting
Madison, Wisconsin, United States