FOG-001 in Locally Advanced or Metastatic Solid Tumors
- Conditions
- CancerColorectal CancerSolid TumorLocally Advanced Solid TumorMetastatic CancerWNT Pathwayβ-cateninBeta-cateninAdenomatous Polyposis ColiAPC
- Interventions
- Registration Number
- NCT05919264
- Lead Sponsor
- Parabilis Medicines, Inc.
- 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.
- Detailed Description
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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 480
- 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
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2d FOG-001 Desmoid Tumors (documented WPAM in APC or CTNNB1 required) Part 1b FOG-001 MSS CRC (known WPAM negative participants are not eligible) Part 1c FOG-001 Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required) Part 1d FOG-001 Desmoid Tumors (documented WPAM in APC or CTNNB1 required) Part 1e-1 FOG-001 Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status Part 1e-2 FOG-001 Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status Part 1f-2 FOG-001 Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible) Part 1f-3 FOG-001 MSS CRC (known WPAM negative participants are not eligible) Part 1f-3 Trifluridine/tipiracil MSS CRC (known WPAM negative participants are not eligible) Part 1f-3 Bevacizumab MSS CRC (known WPAM negative participants are not eligible) Part 2a FOG-001 MSS CRC, irrespective of WPAM status Part 2b FOG-001 Solid Tumors with documented WPAM Part 2c FOG-001 Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required) Part 2e FOG-001 Metastatic Castration-Resistant Prostate Cancer (documented WPAM in APC or CTNNB1 required) Part 2f-1 FOG-001 MSS CRC (known WPAM negative participants are not eligible) Part 2f-1 mFOLFOX-6 MSS CRC (known WPAM negative participants are not eligible) Part 2f-1 Bevacizumab MSS CRC (known WPAM negative participants are not eligible) Part 2f-2 FOG-001 Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible) Part 2f-2 Nivolumab Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible) Part 2f-3 FOG-001 MSS CRC (known WPAM negative participants are not eligible) Part 1a FOG-001 Solid Tumors with any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (CRC), irrespective of WPAM status Part 1f-1 FOG-001 MSS CRC (known WPAM negative participants are not eligible) Part 1f-1 mFOLFOX-6 MSS CRC (known WPAM negative participants are not eligible) Part 1f-1 Bevacizumab MSS CRC (known WPAM negative participants are not eligible) Part 1f-2 Nivolumab Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible) Part 2f-3 Trifluridine/tipiracil MSS CRC (known WPAM negative participants are not eligible) Part 2f-3 Bevacizumab MSS CRC (known WPAM negative participants are not eligible)
- Primary Outcome Measures
Name Time Method 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
- Secondary Outcome Measures
Name Time Method Maximum observed plasma concentration (Cmax) of FOG-001 and associated metabolites During first 2 cycles (56 days) Time to achieve Cmax (Tmax) of FOG-001 and associated metabolites in plasma During first 2 cycles (56 days) Area under the plasma concentration-time curve (AUC) of FOG-001 and associated metabolites During first 2 cycles (56 days) Plasma trough concentration (Ctrough) of FOG-001 and associated metabolites During first 2 cycles (56 days) Clearance (CL) of FOG-001 from the plasma During first 2 cycles (56 days) Volume of distribution of FOG-001 During first 2 cycles (56 days) During dose escalation select the preliminary recommended Phase 2 dose and dosing schedule of study drug Rate of DLTs across dose levels During Cycle 1 (28 days) 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 63 days until study completion, approximately 10 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 63 days until study completion, approximately 10 months on average Time from initial objective response (partial response or complete response) to disease progression
During dose escalation and expansion describe Progression Free Survival From date of randomization until the date of first disease progression, an average of 10 months Progression Free Survival (PFS) using RECIST v1.1
During dose escalation and expansion describe the Disease Control Rate using RECIST v1.1 Every 63 days until study completion, approximately 10 months on average The rate of objective responses (Stable, Partial, \& Complete) using RECIST v1.1
During dose escalation and expansion describe the Time To Progression using RECIST v1.1 From date of randomization until the date of first disease progression, an average of 10 months Time To Progression (TTP) using RECIST v1.1
During dose escalation and expansion describe radiographic Progression Free Survival for participants with prostate cancer From date of randomization until the date of first disease progression, an average of 10 months Radiographic Progression Free Survival (rPFS) using PCWG3 assessment criteria
Trial Locations
- Locations (9)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics, LLC
🇺🇸San Antonio, Texas, United States
Honor Health
🇺🇸Scottsdale, Arizona, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States