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NCT05919264PHASE1, PHASE2Recruiting

FOG-001 in Locally Advanced or Metastatic Solid Tumors

Parabilis Medicines, Inc.

Start Date

5/23/2023

Completion Date

8/31/2027

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).

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), and FAP, a disorder of this pathway characterized by a germline mutation in the APC gene.

Eligibility Criteria

Age Range: 18 years to No maximum

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 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 Exclusion Criteria: * 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.

Interventions

DRUG

FOG-001

DRUG

mFOLFOX-6

DRUG

Nivolumab

DRUG

Trifluridine/tipiracil

DRUG

Bevacizumab

DRUG

FOG-001

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Conditions

CancerColorectal CancerSolid TumorLocally Advanced Solid TumorMetastatic CancerWNT PathwayHCCDesmoidMicrosatellite Stable Colorectal CancerMetastatic Castration-resistant Prostate CancerFamilial Adenomatous Polyposis (FAP)Endometrial CarcinomaProstate CancerMicrosatellite Instability-High Colorectal CancerAdamantinomatous Craniopharyngioma

Locations

Mayo Clinic

Phoenix, Arizona 85054

United States

Honor Health

Scottsdale, Arizona 85258

United States

Arizona Cancer Center at University of Arizona

Tucson, Arizona 85719

United States

University of California, Los Angeles (UCLA)

Los Angeles, California 90095

United States

Stanford Cancer Institute, Stanford University

Palo Alto, California 94304

United States

University of California San Francisco, Helen Diller Family Comprehensive Cancer Center

San Francisco, California 94158

United States

Sarcoma Oncology Center

Santa Monica, California 90403

United States

University of Colorado

Aurora, Colorado 80045

United States

Yale University School of Medicine

New Haven, Connecticut 06520

United States

Johns Hopkins University, Sibley Memorial Hospital

Washington D.C., District of Columbia 20016

United States

Mayo Clinic

Jacksonville, Florida 32224

United States

Florida Cancer Specialists

Lake Mary, Florida 32746

United States

Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland 21287

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02215

United States

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota 55455

United States

Mayo Clinic

Rochester, Minnesota 55905

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

Duke University

Durham, North Carolina 27705

United States

University Hospitals Cleveland Medical Center, Seidman Cancer Center

Cleveland, Ohio 44106

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Oregon Health and Science University

Portland, Oregon 97239

United States

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania 19104

United States

University of Pittsburgh Medical Center, Hillman Cancer Center

Pittsburgh, Pennsylvania 15232

United States

Sarah Cannon Research Institute

Nashville, Tennessee 37203

United States

Vanderbilt Ingram Cancer Center

Nashville, Tennessee 37232

United States

The University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas 78229

United States

University of Virginia

Charlottesville, Virginia 22908

United States

University of Wisconsin, Carbone Cancer Center

Madison, Wisconsin 53705

United States

Integrated Clinical Oncology Network (ICON)

South Brisbane, Queensland 4101

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia