FOG-001 in Locally Advanced or Metastatic Solid Tumors

Purpose

The goal of this clinical trial is to determine if FOG-001 is safe and effective in participants with locally advanced or metastatic cancer.

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1a 		Solid Tumors with any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (CRC), irrespective of WPAM status
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 1b 		MSS CRC (known WPAM negative participants are not eligible)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 1c 		Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 1d 		Desmoid Tumors (documented WPAM in APC or CTNNB1 required)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 1e-1 		Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 1e-2 		Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 1f-1 		MSS CRC (known WPAM negative participants are not eligible)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
  • Drug: mFOLFOX-6
    mFOLFOX-6 will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Leucovorin, 5-fluorouracil, Oxaliplatin
  • Drug: Bevacizumab
    Bevacizumab will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Avastin
Experimental
Part 1f-2 		Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
  • Drug: Nivolumab
    Nivolumab will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Opdivo
Experimental
Part 1f-3 		MSS CRC (known WPAM negative participants are not eligible)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
  • Drug: Trifluridine/tipiracil
    Trifluridine/tipiracil will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Lonsurf
  • Drug: Bevacizumab
    Bevacizumab will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Avastin
Experimental
Part 2a 		MSS CRC, irrespective of WPAM status
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 2b 		Solid Tumors with documented WPAM
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 2c 		Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 2d 		Desmoid Tumors (documented WPAM in APC or CTNNB1 required)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 2e 		Metastatic Castration-Resistant Prostate Cancer (documented WPAM in APC or CTNNB1 required)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
Experimental
Part 2f-1 		MSS CRC (known WPAM negative participants are not eligible)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
  • Drug: mFOLFOX-6
    mFOLFOX-6 will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Leucovorin, 5-fluorouracil, Oxaliplatin
  • Drug: Bevacizumab
    Bevacizumab will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Avastin
Experimental
Part 2f-2 		Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
  • Drug: Nivolumab
    Nivolumab will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Opdivo
Experimental
Part 2f-3 		MSS CRC (known WPAM negative participants are not eligible)
  • Drug: FOG-001
    FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
  • Drug: Trifluridine/tipiracil
    Trifluridine/tipiracil will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Lonsurf
  • Drug: Bevacizumab
    Bevacizumab will be administered per the prescribing information in combination with FOG-001
    Other names:
    • Avastin

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Samuel Klempner, MD
617-724-4000

More Details

Status
Recruiting
Sponsor
Parabilis Medicines, Inc.

Study Contact

Clinical Trial Inquiries
(857) 259-6305
clinicaltrials@parabilismed.com

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).