CancerPhase 1/2NCT05919264
FOG-001 in Locally Advanced or Metastatic Solid Tumors
A Phase 1/2 study testing FOG-001, mFOLFOX-6 and Nivolumab in people with Cancer and Colorectal Cancer, run by Parabilis Medicines, Inc. at 33 sites in 2 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Colorectal Cancer, Solid Tumor
- What is being tested?
- FOG-001, mFOLFOX-6 and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 619 participants
- Where
- 33 sitesin 2 countries
- Study dates
- 23 May 2023to 31 Aug 2027
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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.
Trial locations and contacts
33 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
33 sites in 2 countries
United States31 sites, 30 recruiting
- Recruiting
University of Colorado
Aurora, Colorado, 80045
Breelyn Wilky, MD, 305-243-1287
- Recruiting
Johns Hopkins University, The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Mike J Pishvaian, MD/PhD, 410-955-8964
Eric Christenson, MD, 410-955-8964
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Samuel Klempner, MD, 617-724-4000
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Candace Haddox, MD, 617-632-3000
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Matthew Reilley, MD, 978-852-1310
- Recruiting
University Hospitals Cleveland Medical Center, Seidman Cancer Center
Cleveland, Ohio, 44106
David Bajor, MD, 216-765-9033
- Recruiting
Cleveland Clinic
Cleveland, Ohio, 44195
Wen Wee Ma, MBBS, 216-444-2200
Dale Shepard, MD, PhD, (216) 444-2200
- Recruiting
Duke University
Durham, North Carolina, 27705
Niharika Mettu, MD, 919-684-6342
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Jordi Rodon Ahnert, MD/PhD, 713-792-5603
- Recruiting
Mayo Clinic
Jacksonville, Florida, 32224
Conor O'Donnell, MD, 904-953-6870
- Terminated
Florida Cancer Specialists
Lake Mary, Florida, 32746
- Recruiting
University of California, Los Angeles (UCLA)
Los Angeles, California, 90095
Randy Hecht, MD, 310-829-5471
- Recruiting
University of Wisconsin, Carbone Cancer Center
Madison, Wisconsin, 53705
Jeremy Kratz, MD, 608-263-1300
- Recruiting
M Health Fairview University of Minnesota Medical Center
Minneapolis, Minnesota, 55455
Ajay Prakash, MD/PhD, 612-273-8383
- Recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Meredith S Pelster, MD, 615-329-6862
- Recruiting
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
Kristen Ciombor, MD, 615-322-3000
- Recruiting
Yale University School of Medicine
New Haven, Connecticut, 06520
Michael Cecchini, MD, 415-302-7807
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Rona Yaeger, MD, 646-888-5109
- Recruiting
Stanford Cancer Institute, Stanford University
Palo Alto, California, 94304
Nam Bui, 650-498-6000
- Recruiting
University of Pennsylvania, Perelman School of Medicine
Philadelphia, Pennsylvania, 19104
Mark O'Hara, MD, 215-662-4646
- Recruiting
Mayo Clinic
Phoenix, Arizona, 85054
Mahesh Seetharam, MD, 480-301-8000
- Recruiting
University of Pittsburgh Medical Center, Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Dennis J Hsu, MD, 412-623-1722
- Recruiting
Oregon Health and Science University
Portland, Oregon, 97239
Shivaani Kummar, MD, 503-494-8534
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Hao Xie, MD, 504-284-2511
- Recruiting
South Texas Accelerated Research Therapeutics, LLC
San Antonio, Texas, 78229
Kyriakos Papadopoulos, MD, 210-593-5255
- Recruiting
University of California San Francisco, Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94158
Phu Lam, 888-689-8273
- Recruiting
Sarcoma Oncology Center
Santa Monica, California, 90403
Sant Chawla, MD, 301-552-9999
- Recruiting
Honor Health
Scottsdale, Arizona, 85258
Sunil Sharma, MD, 480-323-1350
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Moh'd Khushman, MD, 314-362-9115
- Recruiting
Arizona Cancer Center at University of Arizona
Tucson, Arizona, 85719
Aaron Scott, MD, 520-694-2873
- Recruiting
Johns Hopkins University, Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Mike J Pishvaian, MD/PhD, 202-804-3343
Australia2 sites, 2 recruiting
- Recruiting
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000
Jeremy Lewin, MD, +61385595000
- Recruiting
Integrated Clinical Oncology Network (ICON)
South Brisbane, Queensland, 4101
Vladimir Andelkovic, MD, +61755198211
About this study
Official title: A Phase 1/2 Study of FOG-001 in Participants With Locally Advanced or Metastatic Solid Tumors
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).
Read the 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.
- Conditions
- Cancer, Colorectal Cancer, Solid Tumor, Locally Advanced Solid Tumor, Metastatic Cancer, WNT Pathway
- Being tested
- FOG-001, mFOLFOX-6, Nivolumab, Trifluridine/tipiracil, Bevacizumab
- 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
- Medical subject headings
- Neoplasms, Colorectal Neoplasms, Neoplasm Metastasis, Desmoid Tumors, Adenomatous Polyposis Coli, Endometrial Neoplasms, Prostatic Neoplasms, Craniopharyngioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FOG-001Drug
FOG-001 will be administered IV at assigned doses in continuous cycles of 28 days
mFOLFOX-6Drug
Also called Leucovorin, 5-fluorouracil, Oxaliplatin
mFOLFOX-6 will be administered per the prescribing information in combination with FOG-001
NivolumabDrug
Also called Opdivo
Nivolumab will be administered per the prescribing information in combination with FOG-001
Trifluridine/tipiracilDrug
Also called Lonsurf
Trifluridine/tipiracil will be administered per the prescribing information in combination with FOG-001
BevacizumabDrug
Also called Avastin
Bevacizumab will be administered per the prescribing information in combination with FOG-001
FOG-001Drug
FOG-001 will be administered subcutaneous at assigned doses in continuous cycles of 28 days
| Study group | Role | What they receive |
|---|---|---|
| Part 1a | Experimental | Solid Tumors with any WNT-Pathway Activating Mutation (WPAM) or Microsatellite Stable (MSS) Colorectal Cancer (CRC), irrespective of WPAM status Receives: Drug: FOG-001 |
| Part 1b | Experimental | MSS CRC (known WPAM negative participants are not eligible) Receives: Drug: FOG-001 |
| Part 1c | Experimental | Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required) Receives: Drug: FOG-001 |
| Part 1d-1 | Experimental | Desmoid Tumors Receives: Drug: FOG-001 |
| Part 1d-2 | Experimental | Desmoid Tumors Receives: Drug: FOG-001 |
| Part 1f-1 | Experimental | MSS CRC (known WPAM negative participants are not eligible) Receives: 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) Receives: Drug: FOG-001; Drug: Nivolumab |
| Part 1f-3 | Experimental | MSS CRC (known WPAM negative participants are not eligible) Receives: Drug: FOG-001; Drug: Trifluridine/tipiracil; Drug: Bevacizumab |
| Part 1g | Experimental | Solid Tumors with documented WPAM (known WPAM negative participants are not eligible) Receives: Drug: FOG-001 |
| Part 1h | Experimental | Desmoid Tumors Receives: Drug: FOG-001 |
| Part 1i | Experimental | Familial adenomatous polyposis (FAP) Receives: Drug: FOG-001 |
| Part 2a | Experimental | MSS CRC, irrespective of WPAM status Receives: Drug: FOG-001 |
| Part 2b | Experimental | Solid Tumors with documented WPAM Receives: Drug: FOG-001 |
| Part 2c | Experimental | Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required) Receives: Drug: FOG-001 |
| Part 2d | Experimental | Desmoid Tumors Receives: Drug: FOG-001 |
| Part 2e | Experimental | Metastatic Castration-Resistant Prostate Cancer (documented WPAM in APC or CTNNB1 required) Receives: Drug: FOG-001 |
| Part 2f-1 | Experimental | MSS CRC (known WPAM negative participants are not eligible) Receives: 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) Receives: Drug: FOG-001; Drug: Nivolumab |
| Part 2f-3 | Experimental | MSS CRC (known WPAM negative participants are not eligible) Receives: Drug: FOG-001; Drug: Trifluridine/tipiracil; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Through study completion, an average of 10 months
During dose escalation characterize dose-limiting toxicities (DLTs)
Incidence of DLTs
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: During first 2 cycles (56 days)
Time to achieve Cmax (Tmax) of FOG-001 and associated metabolites in plasma
Measured: During first 2 cycles (56 days)
Area under the plasma concentration-time curve (AUC) of FOG-001 and associated metabolites
Measured: During first 2 cycles (56 days)
Plasma trough concentration (Ctrough) of FOG-001 and associated metabolites
Measured: During first 2 cycles (56 days)
Clearance (CL) of FOG-001 from the plasma
Measured: During first 2 cycles (56 days)
Volume of distribution of FOG-001
Measured: During first 2 cycles (56 days)
During dose escalation select the preliminary recommended Phase 2 dose and dosing schedule of study drug
Measured: Through Part 1 study completion
Rate of DLTs across dose levels
Measured: During Cycle 1 (28 days)
During dose escalation Part 1b to evaluate the pharmacodynamic activity in tumors
Change in tumor Myc expression (on-study compared to baseline)
Measured: During first 2 cycles (56 days)
During dose escalation and expansion to describe Best Overall Response Rate using RECIST v1.1
Best response to treatment using RECIST v1.1
Measured: Every 63 days until study completion, approximately 10 months on average
During dose escalation and expansion to describe Duration of Response using RECIST v1.1
Time from initial objective response (partial response or complete response) to disease progression
Measured: Every 63 days until study completion, approximately 10 months on average
During dose escalation and expansion describe Progression Free Survival
Progression Free Survival (PFS) using RECIST v1.1
Measured: From date of randomization until the date of first disease progression, an average of 10 months
During dose escalation and expansion describe the Disease Control Rate using RECIST v1.1
The rate of objective responses (Stable, Partial, \& Complete) using RECIST v1.1
Measured: Every 63 days until study completion, approximately 10 months on average
During dose escalation and expansion describe the Time To Progression using RECIST v1.1
Time To Progression (TTP) using RECIST v1.1
Measured: From date of randomization until the date of first disease progression, an average of 10 months
During dose escalation and expansion describe radiographic Progression Free Survival for participants with prostate cancer
Radiographic Progression Free Survival (rPFS) using PCWG3 assessment criteria
Measured: From date of randomization until the date of first disease progression, an average of 10 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2023
- Study start23 May 2023
- Primary completion1 Apr 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 619 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Parabilis Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Benjamin Oshrine, Study chair, Parabilis Medicines, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05919264
- Sponsor's protocol ID
- FOG-001-101
- Status last verified
- Oct 2026
- First submitted
- 19 May 2023
- Last updated
- 7 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Habault J, Franco JL, Ha S, Schneider JA, Voisin M, Wise DR, Wong KK, Garabedian MJ, Kirshenbaum K, Logan SK. In Vivo Efficacy of a Macrocyclic Peptoid-Peptide Hybrid That Selectively Modulates the Beta-Catenin/TCF Interaction to Inhibit Prostate Cancer. Prostate. 2025 May;85(7):646-658. doi: 10.1002/pros.24868. Epub 2025 Feb 16.
PubMed 39956770