FOG-001 in Locally Advanced or Metastatic Solid Tumors

NCT05919264
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Phase
Phase 1/Phase 2
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Recruitment status
Recruiting
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Participants
619
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Lead sponsor
Parabilis Medicines, Inc.
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Start date
2023-05-23
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Number of sites
33
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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).
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Short title
FOG-001 in Locally Advanced or Metastatic Solid Tumors
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Official title
A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2027-08-31
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First posted
2023-06-26
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Registry last updated
2026-08-17
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Primary completion date
2027-04-01
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Start date
2023-05-23
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Participants
619
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Participant count basis
Estimated
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Planned participants
619
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Protocol amendments
7
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Number of sites
33
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Parabilis Medicines, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05919264
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ClinicalTrials.gov ID
NCT05919264
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0

    Timeframe: Through study completion, an average of 10 months

    Number and severity of treatment emergent adverse events as assessed by CTCAE v5.0

  2. During dose escalation characterize dose-limiting toxicities (DLTs)

    Timeframe: 1 treatment cycle (28 days)

    Incidence of DLTs

  3. During dose expansion describe the Overall Response Rate using RECIST v1.1

    Timeframe: Every 63 days until study completion, approximately 10 months on average

    The rate of objective responses (Partial \& Complete) using RECIST v1.1

  4. During dose expansion describe the Disease Control Rate using RECIST v1.1 (Part 2a only)

    Timeframe: 4 months

    The rate of objective responses (Stable, Partial, \& Complete) using RECIST v1.1

  5. During dose expansion describe the PSA30 response rate for participants with prostate cancer

    Timeframe: 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

  1. Maximum observed plasma concentration (Cmax) of FOG-001 and associated metabolites

    Timeframe: During first 2 cycles (56 days)

  2. Time to achieve Cmax (Tmax) of FOG-001 and associated metabolites in plasma

    Timeframe: During first 2 cycles (56 days)

  3. Area under the plasma concentration-time curve (AUC) of FOG-001 and associated metabolites

    Timeframe: During first 2 cycles (56 days)

  4. Plasma trough concentration (Ctrough) of FOG-001 and associated metabolites

    Timeframe: During first 2 cycles (56 days)

  5. Clearance (CL) of FOG-001 from the plasma

    Timeframe: During first 2 cycles (56 days)

  6. Volume of distribution of FOG-001

    Timeframe: During first 2 cycles (56 days)

  7. During dose escalation select the preliminary recommended Phase 2 dose and dosing schedule of study drug

    Timeframe: Through Part 1 study completion

  8. Rate of DLTs across dose levels

    Timeframe: During Cycle 1 (28 days)

  9. During dose escalation Part 1b to evaluate the pharmacodynamic activity in tumors

    Timeframe: During first 2 cycles (56 days)

    Change in tumor Myc expression (on-study compared to baseline)

  10. During dose escalation and expansion to describe Best Overall Response Rate using RECIST v1.1

    Timeframe: Every 63 days until study completion, approximately 10 months on average

    Best response to treatment using RECIST v1.1

  11. During dose escalation and expansion to describe Duration of Response using RECIST v1.1

    Timeframe: Every 63 days until study completion, approximately 10 months on average

    Time from initial objective response (partial response or complete response) to disease progression

  12. During dose escalation and expansion describe Progression Free Survival

    Timeframe: From date of randomization until the date of first disease progression, an average of 10 months

    Progression Free Survival (PFS) using RECIST v1.1

  13. During dose escalation and expansion describe the Disease Control Rate using RECIST v1.1

    Timeframe: Every 63 days until study completion, approximately 10 months on average

    The rate of objective responses (Stable, Partial, \& Complete) using RECIST v1.1

  14. During dose escalation and expansion describe the Time To Progression using RECIST v1.1

    Timeframe: From date of randomization until the date of first disease progression, an average of 10 months

    Time To Progression (TTP) using RECIST v1.1

  15. During dose escalation and expansion describe radiographic Progression Free Survival for participants with prostate cancer

    Timeframe: 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

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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.
Sources for eligibility
clinicaltrials.gov

  • Mayo ClinicPhoenix, United StatesRecruiting
  • Honor HealthScottsdale, United StatesRecruiting
  • Arizona Cancer Center at University of ArizonaTucson, United StatesRecruiting
  • University of California, Los Angeles (UCLA)Los Angeles, United StatesRecruiting
  • Stanford Cancer Institute, Stanford UniversityPalo Alto, United StatesRecruiting
  • University of California San Francisco, Helen Diller Family Comprehensive Cancer CenterSan Francisco, United StatesRecruiting
  • Sarcoma Oncology CenterSanta Monica, United StatesRecruiting
  • University of ColoradoAurora, United StatesRecruiting
  • Yale University School of MedicineNew Haven, United StatesRecruiting
  • Johns Hopkins University, Sibley Memorial HospitalWashington D.C., United StatesRecruiting
  • Mayo ClinicJacksonville, United StatesRecruiting
  • Florida Cancer SpecialistsLake Mary, United StatesTerminated
  • Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer CenterBaltimore, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • Dana Farber Cancer InstituteBoston, United StatesRecruiting
  • M Health Fairview University of Minnesota Medical CenterMinneapolis, United StatesRecruiting
  • Mayo ClinicRochester, United StatesRecruiting
  • Washington University School of MedicineSt Louis, United StatesRecruiting
  • Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • Duke UniversityDurham, United StatesRecruiting
  • University Hospitals Cleveland Medical Center, Seidman Cancer CenterCleveland, United StatesRecruiting
  • Cleveland ClinicCleveland, United StatesRecruiting
  • Oregon Health and Science UniversityPortland, United StatesRecruiting
  • University of Pennsylvania, Perelman School of MedicinePhiladelphia, United StatesRecruiting
  • University of Pittsburgh Medical Center, Hillman Cancer CenterPittsburgh, United StatesRecruiting

And 8 more, listed on the interactive page.

Sources for sites
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Sources for references
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