Mass General - Division of Clinical Research

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

Arm	Description	Assigned 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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.