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

NCT04825288 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2020-PT049
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 28

Brief Summary

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).

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (2)

• 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.

  Primary Endpoint for Phase I portion

  44 days

• Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0

  Safety endpoints will be evaluated for number of subjects by monitoring treatment emergent adverse events (TEAE) from clinical and laboratory reporting as assessed by CTCAE v4.0.

  28 weeks

Secondary Outcomes (12)

• Progression Free Survival

  From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first, assessed up to 24 weeks.

• Overall Survival (OS)

  From baseline until the date of death (from any cause) assessed up to 24 weeks.

• Objective Response Rate

  Assessment every 8 weeks after initial response assessed up to 24 weeks.

• Time to Treatment Failure

  From baseline to treatment discontinuation (any cause) assessed up to 24 weeks

• Percentage of Patients with Clinical Benefit Response

  Baseline to weeks 8, 16 and 24. CBR will be defined as a composite measure consisting of change in lean body mass (LBM) and change in quality of life

Other Outcomes (2)

• Results of a symptom questionnaire will be summarized by treatment arm at various post-infusion time points and compared over time

  At various post-infusion time points assessed up to 22 weeks

• Cardiotoxicity measured by the number of required ECGs and cardiotoxicity related events summarized by treatment arm and compared over time

  Compared over time, assessed up to 22 weeks

Study Arms (2)

Arm 1

ACTIVE COMPARATOR

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).

Biological: XB2001 or Placebo

Arm 2

PLACEBO COMPARATOR

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).

Biological: XB2001 or Placebo

Interventions

XB2001 or Placebo 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 1; Arm 2

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Clinically significant decrease in performance status (medical records) within 2 weeks of intended first dose administration
• Clinically significant GI disorders
• 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.

Sponsors & Collaborators

• XBiotech, Inc.: lead

Study Sites (28)

Arizona Oncology Associates

Tucson, Arizona, 85711, United States

Location

Disney Family Cancer Center at Providence St. Joseph Medical Center

Burbank, California, 91505, United States

Location

TOI Clinical Research

Cerritos, California, 90703, United States

Location

Providence St. Joseph Heritage - Fullerton, CA

Fullerton, California, 92835, United States

Location

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

Location

Grand Valley Oncology

Grand Junction, Colorado, 81505, United States

Location

Sarah Cannon - Florida Cancer Specialists

Lake Mary, Florida, 32746, United States

Location

Mt. Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Sarasota Memorial Hospital

Sarasota, Florida, 34239, United States

Location

Goshen Center for Cancer Care

Goshen, Indiana, 46526, United States

Location

Alliance for Multispecialty Research, LLC

Merriam, Kansas, 66204, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Revive Research - Farmington Hills

Farmington Hills, Michigan, 48334, United States

Location

Revive Research - Sterling Heights

Sterling Heights, Michigan, 48126, United States

Location

St. Vincent Frontier Cancer Center

Billings, Montana, 59102, United States

Location

Summit Medical Group

Florham Park, New Jersey, 07932, United States

Location

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

Location

Montefiore Einstein Medical Center

The Bronx, New York, 10461, United States

Location

Providence Portland

Portland, Oregon, 97213, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Tennessee Medical Center Cancer Institute

Knoxville, Tennessee, 37920, United States

Location

Sarah Cannon - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

Community Cancer Trials of Utah

Ogden, Utah, 84405, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Bon Secours St. Francis Cancer Center

Midlothian, Virginia, 23114, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Study Officials

• David J Park

  Providence St. Joseph Heritage

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded study
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 1, 2021
• Study Start: May 27, 2021
• Primary Completion: October 26, 2023
• Study Completion: June 10, 2025
• Last Updated: February 28, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (28)