XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer

NCT ID: NCT04825288

Last Updated: 2025-02-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

76 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-05-27

Study Completion Date

2025-06-10

Brief Summary

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This trial will include 2 portions (phase 1 and phase 2).

The first portion will be a Phase I, open label, dose escalation study to establish the maximum tolerated dose (MTD) of XB2001 as measured by Dose-Limiting Toxicity (DLT), in combination with ONIVYDE + LV + 5-FU chemotherapy regimen in patients with advanced pancreatic cancer and to determine the recommended dose for the subsequent Phase 2 study.

The phase 2 portion will be implemented with the maximum established tolerated dose (MTD) of XB2001. The target enrollment in the phase 2 portion is 60 patients which will be randomized on a 1:1 basis to XB2001 plus ONIVYDE + LV + 5-FU (Arm 1) or placebo plus ONIVYDE + LV + 5-FU (Arm 2).

Detailed Description

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Study Title: A Phase I/II randomized, double-blind, placebo-controlled trial (1-BETTER) examining XB2001 (anti-IL-1⍺ True Human antibody) in combination with ONIVYDE + 5-FU/LV (+folinic acid) in advanced pancreatic cancer

Sponsor: XBiotech USA, Inc.

Study Chair: David Park, M.D.

Sample Size: Approximately 69 patients will be enrolled in the USA (at least 9 patients in the open label phase 1 portion and 60 patients in the randomized phase 2 portion)

Approximate Duration:

This trial will include 2 phases. The first portion will be a Phase I, open label, dose escalation study evaluating the safety, tolerability and establishing the Maximum Tolerated Dose (MTD) of XB2001 in at least nine patients with metastatic pancreatic adenocarcinoma who are receiving ONIVYDE + Leucovorin l + d racemic + 5-Fluorouracil chemotherapy treatment. The duration for each patient in the Phase I portion will be 14 days (1 treatment cycle) in which they will be given one intravenous dose of XB2001 prior to receiving ONIVYDE + Leucovorin l + d racemic + 5-Fluorouracil chemotherapy treatment and assessed for Dose Limited Toxicities (DLT). The Phase II portion will be implemented following the completion of the Phase I portion and declaration of the MTD. The duration of subject participation in the randomized, double-blind, placebo-controlled Phase II portion of the trial is approximately 28 weeks: including a screening period of up to 30 days, and 24-week treatment period. All study subjects can continue treatment with XB2001 in an open label extension, for as long as they are judged to be benefitting clinically and have had no unacceptable toxicities.

Conditions

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Pancreatic Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Subjects in phase II portion will be randomized on a 1:1 basis to XB2001 plus ONIVYDE + LV + 5-FU (Arm 1) or placebo plus ONIVYDE + LV + 5-FU (Arm 2).
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Double-blinded study

Study Groups

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Arm 1

XB2001 + ONIVYDE + 5-FU + LV combination therapy administered for 12 cycles of treatment

• Arm 1 Treatment Cycle: Patients randomized to this arm will receive the following treatments every 2 weeks: XB2001 MTD as an intravenous infusion over up to 60 minutes, followed by ONIVYDE 70 mg/m2 intravenously over 90 minutes, followed by leucovorin l + d racemic 400 mg/m2 intravenously over 30 minutes, followed by 5-Fluorouracil 2400mg/m2 intravenously over 46 hours. Therapy will be administered every 2 weeks (2 weeks = 1 cycle).

Group Type ACTIVE_COMPARATOR

XB2001 or Placebo

Intervention Type BIOLOGICAL

XB2001 is a True Human monoclonal antibody that blocks the biological activity of IL-1α with a high degree of affinity and specificity. IL-1⍺ is a key mediator of inflammatory responses and is implicated in the pathophysiology of various diseases, including cancer, cardiovascular and rheumatologic diseases. Ample evidence supports targeting IL-1⍺ to block pathological inflammatory processes associated with many diseases.

Arm 2

Placebo + ONIVYDE + 5-FU + LV combination therapy administered for 12 cycles of treatment

• Arm 2 Treatment Cycle: Patients randomized to this arm will receive the following treatments every 2 weeks: Placebo as an intravenous infusion over up to 60 minutes, followed by ONIVYDE 70 mg/m2 intravenously over 90 minutes, followed by leucovorin l + d racemic 400 mg/m2 intravenously over 30 minutes, followed by 5-fluorouracil 2400 mg/m2 intravenously over 46 hours. Therapy will be administered every 2 weeks (2 weeks = 1 cycle).

Group Type PLACEBO_COMPARATOR

XB2001 or Placebo

Intervention Type BIOLOGICAL

XB2001 is a True Human monoclonal antibody that blocks the biological activity of IL-1α with a high degree of affinity and specificity. IL-1⍺ is a key mediator of inflammatory responses and is implicated in the pathophysiology of various diseases, including cancer, cardiovascular and rheumatologic diseases. Ample evidence supports targeting IL-1⍺ to block pathological inflammatory processes associated with many diseases.

Interventions

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XB2001 or Placebo

XB2001 is a True Human monoclonal antibody that blocks the biological activity of IL-1α with a high degree of affinity and specificity. IL-1⍺ is a key mediator of inflammatory responses and is implicated in the pathophysiology of various diseases, including cancer, cardiovascular and rheumatologic diseases. Ample evidence supports targeting IL-1⍺ to block pathological inflammatory processes associated with many diseases.

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed pancreatic adenocarcinoma of exocrine pancreas that is metastatic, unresectable, or recurrent
* At least one measurable lesion according to Response Evaluation Criteria in Solid Tumor V1.1
* Documented disease progression after one prior gemcitabine-based therapy OR one FOLFIRINOX and gemcitabine combination therapy
* Eastern Cooperative Oncology Group (ECOG) performance of 0 or 1 or Karnofsky performance status (KPS) ≥ 70
* Adequate hepatic, renal and bone marrow function

Exclusion Criteria

* Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration
* Clinically significant GI disorders
* Severe arterial thromboembolic events less than 6 months before inclusion
* Prior Whole Brain Radiation Therapy (WBRT)
* Evidence of brain metastases
* NYHA Class III or IV congestive heart failure, ventricular arrhythmias or uncontrolled blood pressure (defined as ≥ 160/100 mm Hg)
* Use of strong CYP3A4 inducers or inhibitors and/or UGT1A1 inhibitors within 14 days prior to Visit 1/Baseline visit.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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XBiotech, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David J Park

Role: STUDY_CHAIR

Providence St. Joseph Heritage

Locations

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Arizona Oncology Associates

Tucson, Arizona, United States

Site Status

Disney Family Cancer Center at Providence St. Joseph Medical Center

Burbank, California, United States

Site Status

TOI Clinical Research

Cerritos, California, United States

Site Status

Providence St. Joseph Heritage - Fullerton, CA

Fullerton, California, United States

Site Status

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status

Grand Valley Oncology

Grand Junction, Colorado, United States

Site Status

Sarah Cannon - Florida Cancer Specialists

Lake Mary, Florida, United States

Site Status

Mt. Sinai Comprehensive Cancer Center

Miami Beach, Florida, United States

Site Status

Sarasota Memorial Hospital

Sarasota, Florida, United States

Site Status

Goshen Center for Cancer Care

Goshen, Indiana, United States

Site Status

Alliance for Multispecialty Research, LLC

Merriam, Kansas, United States

Site Status

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Site Status

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status

Revive Research - Farmington Hills

Farmington Hills, Michigan, United States

Site Status

Revive Research - Sterling Heights

Sterling Heights, Michigan, United States

Site Status

St. Vincent Frontier Cancer Center

Billings, Montana, United States

Site Status

Summit Medical Group

Florham Park, New Jersey, United States

Site Status

Stony Brook Cancer Center

Stony Brook, New York, United States

Site Status

Montefiore Einstein Medical Center

The Bronx, New York, United States

Site Status

Providence Portland

Portland, Oregon, United States

Site Status

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

University of Tennessee Medical Center Cancer Institute

Knoxville, Tennessee, United States

Site Status

Sarah Cannon - Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Vanderbilt University

Nashville, Tennessee, United States

Site Status

Mary Crowley Cancer Research

Dallas, Texas, United States

Site Status

Community Cancer Trials of Utah

Ogden, Utah, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Bon Secours St. Francis Cancer Center

Midlothian, Virginia, United States

Site Status

Countries

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United States

Other Identifiers

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2020-PT049

Identifier Type: -

Identifier Source: org_study_id

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