Clinical trial NCT05919264: FOG-001 in Locally Advanced or Metastatic Solid Tumors
Official title: A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Cancer
Colorectal Cancer
Solid Tumor
Locally Advanced Solid Tumor
Metastatic Cancer
WNT Pathway
β-catenin
Beta-catenin
Adenomatous Polyposis Coli
APC
HCC
Desmoid
Microsatellite Stable Colorectal Cancer
Metastatic Castration-resistant Prostate Cancer
FAP
Endometrial Carcinoma
Prostate Cancer
Microsatellite Instability-High Colorectal Cancer
CTNNB1
Adamantinomatous Craniopharyngioma
Keywords: Cancer
Solid Tumor
Locally Advanced Solid Tumor
Metastatic Cancer
WNT Pathway Activating Mutation (WPAM)
Colorectal Cancer (CRC)
Microsatellite Stable (MSS)
Lead sponsor: Parabilis Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-26
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

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 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

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.
* 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.

Primary outcomes:
measure: 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
measure: During dose escalation characterize dose-limiting toxicities (DLTs)
timeFrame: 1 treatment cycle (28 days)
measure: During dose expansion describe the Overall Response Rate using RECIST v1.1
timeFrame: Every 63 days until study completion, approximately 10 months on average
measure: During dose expansion describe the Disease Control Rate using RECIST v1.1 (Part 2a only)
timeFrame: 4 months
measure: 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)
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of FOG-001 and associated metabolites
timeFrame: During first 2 cycles (56 days)
measure: Time to achieve Cmax (Tmax) of FOG-001 and associated metabolites in plasma
timeFrame: During first 2 cycles (56 days)
measure: Area under the plasma concentration-time curve (AUC) of FOG-001 and associated metabolites
timeFrame: During first 2 cycles (56 days)
measure: Plasma trough concentration (Ctrough) of FOG-001 and associated metabolites
timeFrame: During first 2 cycles (56 days)
measure: Clearance (CL) of FOG-001 from the plasma
timeFrame: During first 2 cycles (56 days)
measure: Volume of distribution of FOG-001
timeFrame: During first 2 cycles (56 days)
measure: During dose escalation select the preliminary recommended Phase 2 dose and dosing schedule of study drug Rate of DLTs across dose levels
timeFrame: During Cycle 1 (28 days)
measure: During dose escalation Part 1b to evaluate the pharmacodynamic activity in tumors
timeFrame: During first 2 cycles (56 days)
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health
state: Arizona
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics, LLC
state: Texas
Study officials:
affiliation: Parabilis Medicines, Inc.
name: Marie Nguyen, MD
role: STUDY_CHAIR
References: