FOG-001 in Locally Advanced or Metastatic Solid Tumors

Parabilis Medicines, Inc.

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Solid Tumor; Beta-catenin; FAP; CTNNB1; Locally Advanced Solid Tumor; Adenomatous Polyposis Coli; Metastatic Castration-resistant Prostate Cancer; Cancer; Microsatellite Stable Colorectal Cancer; HCC; WNT Pathway; Endometrial Carcinoma; Metastatic Cancer; Adamantinomatous Craniopharyngioma; APC; Microsatellite Instability-High Colorectal Cancer; Prostate Cancer; Desmoid; β-catenin; Colorectal Cancer

Treatments: Drug: mFOLFOX-6; Drug: Bevacizumab; Drug: Nivolumab; Drug: FOG-001; Drug: Trifluridine/tipiracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT05919264

FOG-001-101

Details and patient eligibility

About

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

Full 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).

Enrollment: 480 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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480 participants in 17 patient groups

Part 1a

Experimental group

Description:

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

Treatment:

Drug: FOG-001

Part 1b

Experimental group

Description:

MSS CRC (known WPAM negative participants are not eligible)

Treatment:

Drug: FOG-001

Part 1c

Experimental group

Description:

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

Treatment:

Drug: FOG-001

Part 1d

Experimental group

Description:

Desmoid Tumors (documented WPAM in APC or CTNNB1 required)

Treatment:

Drug: FOG-001

Part 1e-1

Experimental group

Description:

Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status

Treatment:

Drug: FOG-001

Part 1e-2

Experimental group

Description:

Solid Tumors with documented WPAM or MSS CRC, irrespective of WPAM status

Treatment:

Drug: FOG-001

Part 1f-1

Experimental group

Description:

MSS CRC (known WPAM negative participants are not eligible)

Treatment:

Drug: FOG-001

Drug: Bevacizumab

Drug: mFOLFOX-6

Part 1f-2

Experimental group

Description:

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

Treatment:

Drug: FOG-001

Drug: Nivolumab

Part 1f-3

Experimental group

Description:

MSS CRC (known WPAM negative participants are not eligible)

Treatment:

Drug: Trifluridine/tipiracil

Drug: FOG-001

Drug: Bevacizumab

Part 2a

Experimental group

Description:

MSS CRC, irrespective of WPAM status

Treatment:

Drug: FOG-001

Part 2b

Experimental group

Description:

Solid Tumors with documented WPAM

Treatment:

Drug: FOG-001

Part 2c

Experimental group

Description:

Hepatocellular Carcinoma (documented WPAM in APC or CTNNB1 required)

Treatment:

Drug: FOG-001

Part 2d

Experimental group

Description:

Desmoid Tumors (documented WPAM in APC or CTNNB1 required)

Treatment:

Drug: FOG-001

Part 2e

Experimental group

Description:

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

Treatment:

Drug: FOG-001

Part 2f-1

Experimental group

Description:

MSS CRC (known WPAM negative participants are not eligible)

Treatment:

Drug: FOG-001

Drug: Bevacizumab

Drug: mFOLFOX-6

Part 2f-2

Experimental group

Description:

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

Treatment:

Drug: FOG-001

Drug: Nivolumab

Part 2f-3

Experimental group

Description:

MSS CRC (known WPAM negative participants are not eligible)

Treatment:

Drug: Trifluridine/tipiracil

Drug: FOG-001

Drug: Bevacizumab