A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Parabilis Medicines, Inc.
- Enrollment
- 595
- Locations
- 45
- Primary Endpoint
- During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0
Overview
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 solid tumors.
Detailed Description
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).
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •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):
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.
Arms & Interventions
Part 1a
Solid Tumors with any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (CRC), irrespective of WPAM status
Intervention: FOG-001 (Drug)
Part 1b
MSS CRC (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 2f-2
Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 1f-1
MSS CRC (known WPAM negative participants are not eligible)
Intervention: mFOLFOX-6 (Drug)
Part 2e
Metastatic Castration-Resistant Prostate Cancer (documented WPAM in APC or CTNNB1 required)
Intervention: FOG-001 (Drug)
Part 2f-1
MSS CRC (known WPAM negative participants are not eligible)
Intervention: mFOLFOX-6 (Drug)
Part 2c
Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)
Intervention: FOG-001 (Drug)
Part 2f-1
MSS CRC (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 2d
Desmoid Tumors
Intervention: FOG-001 (Drug)
Part 1g
Solid Tumors with documented WPAM (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 2f-3
MSS CRC (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 1c
Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)
Intervention: FOG-001 (Drug)
Part 1d-1
Desmoid Tumors
Intervention: FOG-001 (Drug)
Part 1h
Desmoid Tumors
Intervention: FOG-001 (Drug)
Part 1d-2
Desmoid Tumors
Intervention: FOG-001 (Drug)
Part 1f-3
MSS CRC (known WPAM negative participants are not eligible)
Intervention: Bevacizumab (Drug)
Part 1f-2
Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)
Intervention: Nivolumab (Drug)
Part 1f-1
MSS CRC (known WPAM negative participants are not eligible)
Intervention: Bevacizumab (Drug)
Part 1f-2
Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 1f-3
MSS CRC (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 1f-1
MSS CRC (known WPAM negative participants are not eligible)
Intervention: FOG-001 (Drug)
Part 2b
Solid Tumors with documented WPAM
Intervention: FOG-001 (Drug)
Part 1f-3
MSS CRC (known WPAM negative participants are not eligible)
Intervention: Trifluridine/tipiracil (Drug)
Part 2a
MSS CRC, irrespective of WPAM status
Intervention: FOG-001 (Drug)
Part 2f-1
MSS CRC (known WPAM negative participants are not eligible)
Intervention: Bevacizumab (Drug)
Part 2f-2
Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)
Intervention: Nivolumab (Drug)
Part 2f-3
MSS CRC (known WPAM negative participants are not eligible)
Intervention: Trifluridine/tipiracil (Drug)
Part 2f-3
MSS CRC (known WPAM negative participants are not eligible)
Intervention: Bevacizumab (Drug)
Outcomes
Primary Outcomes
During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0
Time Frame: 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)
Time Frame: 1 treatment cycle (28 days)
Incidence of DLTs
During dose expansion describe the Overall Response Rate using RECIST v1.1
Time Frame: 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)
Time Frame: 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
Time Frame: 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 Outcomes
- 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)
- 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)
- 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)
- 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 Part 1b to evaluate the pharmacodynamic activity in tumors(During first 2 cycles (56 days))
- 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)
- 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)
- 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)
- 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(Through Part 1 study completion)
- 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))
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)