FOG-001 in Locally Advanced or Metastatic Solid Tumors

NCT05919264 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: FOG-001-101
• Study Type: interventional
• Target: 595
• Locations: 2 countries
• Sites: 33

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.

Conditions

Metastatic Cancer; Prostate Cancer; Microsatellite Instability-High Colorectal Cancer; Cancer; WNT Pathway; Locally Advanced Solid Tumor; Colorectal Cancer; Solid Tumor; HCC; Desmoid; Microsatellite Stable Colorectal Cancer; Metastatic Castration-resistant Prostate Cancer; FAP; Endometrial Carcinoma; Adamantinomatous Craniopharyngioma

Keywords

Cancer; Solid Tumor; Locally Advanced Solid Tumor; Metastatic Cancer; WNT Pathway Activating Mutation (WPAM); Colorectal Cancer (CRC); Microsatellite Stable (MSS); Desmoid; Hepatocellular Carcinoma (HCC); Adenomatous Polyposis Coli (APC); β-catenin; Beta-catenin; CTNNB1

Outcome Measures

Primary Outcomes (5)

• During dose escalation and dose expansion measure incidence and severity of treatment emergent adverse events by CTCAE v5.0

  Number and severity of treatment emergent adverse events as assessed by CTCAE v5.0

  Through study completion, an average of 10 months

• During dose escalation characterize dose-limiting toxicities (DLTs)

  Incidence of DLTs

  1 treatment cycle (28 days)

• During dose expansion describe the Overall Response Rate using RECIST v1.1

  The rate of objective responses (Partial \& Complete) using RECIST v1.1

  Every 63 days until study completion, approximately 10 months on average

• During dose expansion describe the Disease Control Rate using RECIST v1.1 (Part 2a only)

  The rate of objective responses (Stable, Partial, \& Complete) using RECIST v1.1

  4 months

• During dose expansion describe the PSA30 response rate for participants with prostate cancer

  The response to treatment as a 30% or greater reduction in PSA levels from baseline

  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 (15)

• 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)

Study Arms (18)

Part 1a

EXPERIMENTAL

Solid Tumors with any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (CRC), irrespective of WPAM status

Drug: FOG-001

Part 1b

EXPERIMENTAL

MSS CRC (known WPAM negative participants are not eligible)

Drug: FOG-001

Part 1c

EXPERIMENTAL

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

Drug: FOG-001

Part 1d-1

EXPERIMENTAL

Desmoid Tumors

Drug: FOG-001

Part 1d-2

EXPERIMENTAL

Desmoid Tumors

Drug: FOG-001

Part 1f-1

EXPERIMENTAL

MSS CRC (known WPAM negative participants are not eligible)

Drug: FOG-001; Drug: mFOLFOX-6; Drug: Bevacizumab

Part 1f-2

EXPERIMENTAL

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

Drug: FOG-001; Drug: Nivolumab

Part 1f-3

EXPERIMENTAL

MSS CRC (known WPAM negative participants are not eligible)

Drug: FOG-001; Drug: Trifluridine/tipiracil; Drug: Bevacizumab

Part 1g

EXPERIMENTAL

Solid Tumors with documented WPAM (known WPAM negative participants are not eligible)

Drug: FOG-001

Part 1h

EXPERIMENTAL

Desmoid Tumors

Drug: FOG-001

Part 2a

EXPERIMENTAL

MSS CRC, irrespective of WPAM status

Drug: FOG-001

Part 2b

EXPERIMENTAL

Solid Tumors with documented WPAM

Drug: FOG-001

Part 2c

EXPERIMENTAL

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

Drug: FOG-001

Part 2d

EXPERIMENTAL

Desmoid Tumors

Drug: FOG-001

Part 2e

EXPERIMENTAL

Metastatic Castration-Resistant Prostate Cancer (documented WPAM in APC or CTNNB1 required)

Drug: FOG-001

Part 2f-1

EXPERIMENTAL

MSS CRC (known WPAM negative participants are not eligible)

Drug: FOG-001; Drug: mFOLFOX-6; Drug: Bevacizumab

Part 2f-2

EXPERIMENTAL

Solid Tumors with documented WPAM or MSS CRC (known WPAM negative participants are not eligible)

Drug: FOG-001; Drug: Nivolumab

Part 2f-3

EXPERIMENTAL

MSS CRC (known WPAM negative participants are not eligible)

Drug: FOG-001; Drug: Trifluridine/tipiracil; Drug: Bevacizumab

Interventions

FOG-001 DRUG

FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days

Part 1a; Part 1b; Part 1c; Part 1d-1; Part 1d-2; Part 1f-1; Part 1f-2; Part 1f-3; Part 2a; Part 2b; Part 2c; Part 2d; Part 2e; Part 2f-1; Part 2f-2; Part 2f-3

mFOLFOX-6 DRUG

mFOLFOX-6 will be administered per the prescribing information in combination with FOG-001

Also known as: Leucovorin, 5-fluorouracil, Oxaliplatin

Part 1f-1; Part 2f-1

Nivolumab DRUG

Nivolumab will be administered per the prescribing information in combination with FOG-001

Also known as: Opdivo

Part 1f-2; Part 2f-2

Trifluridine/tipiracil DRUG

Trifluridine/tipiracil will be administered per the prescribing information in combination with FOG-001

Also known as: Lonsurf

Part 1f-3; Part 2f-3

Bevacizumab DRUG

Bevacizumab will be administered per the prescribing information in combination with FOG-001

Also known as: Avastin

Part 1f-1; Part 1f-3; Part 2f-1; Part 2f-3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ and marrow function.
• 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).
• 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.
• Histologically, cytologically, or radiographically confirmed HCC with a documented WPAM (by local ctDNA or tumor NGS testing) in APC or CTNNB1
• Desmoid tumor (aggressive fibromatosis)
• 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.
• 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
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Parabilis Medicines, Inc.: lead

Study Sites (33)

Mayo Clinic

Phoenix, Arizona, 85054, United States

RECRUITING

Honor Health

Scottsdale, Arizona, 85258, United States

RECRUITING

Arizona Cancer Center at University of Arizona

Tucson, Arizona, 85719, United States

RECRUITING

University of California, Los Angeles (UCLA)

Los Angeles, California, 90095, United States

RECRUITING

Stanford Cancer Institute, Stanford University

Palo Alto, California, 94304, United States

RECRUITING

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

San Francisco, California, 94158, United States

RECRUITING

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

RECRUITING

Johns Hopkins University, Sibley Memorial Hospital

Washington D.C., District of Columbia, 20016, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

TERMINATED

Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Duke University

Durham, North Carolina, 27705, United States

RECRUITING

University Hospitals Cleveland Medical Center, Seidman Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Oregon Health and Science University

Portland, Oregon, 97239, United States

RECRUITING

University of Pennsylvania, Perelman School of Medicine

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh Medical Center, Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, 78229, United States

RECRUITING

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

University of Wisconsin, Carbone Cancer Center

Madison, Wisconsin, 53705, United States

RECRUITING

Integrated Clinical Oncology Network (ICON)

South Brisbane, Queensland, 4101, Australia

RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

MeSH Terms

Conditions

Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Desmoid Tumors; Endometrial Neoplasms; Prostatic Neoplasms; Craniopharyngioma; Carcinoma, Hepatocellular; Adenomatous Polyposis Coli

Interventions

Leucovorin; Fluorouracil; Oxaliplatin; Nivolumab; trifluridine tipiracil drug combination; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Liver Neoplasms; Liver Diseases; Adenomatous Polyps; Adenoma; Neoplastic Syndromes, Hereditary; Intestinal Polyposis; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jorge Ramos, DO

  Parabilis Medicines, Inc.

  STUDY CHAIR

Central Study Contacts

Clinical Trial Inquiries

CONTACT

(857) 259-6305; clinicaltrials@parabilismed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: June 26, 2023
• Study Start: May 23, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): August 31, 2027
• Last Updated: May 28, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (31); AU (2)