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

NCT04825288 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 2020-PT049
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 30

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.

  The primary objective of the Phase I portion is to identify the MTD of XB2001 when administered in combination with ONIVYDE + LV + 5-FU. The MTD is defined as the highest dose level at which no more than one out of six subjects experience a DLT. If two or more subjects in a cohort of six experience a DLT, the MTD is considered exceeded, and the previous lower dose level will be identified as the MTD. If no DLTs are observed at the highest dose level studied, that dose will be used for Phase II. A DLT is defined as any Grade 3-4 adverse event (per NCI CTCAE v5.0) occurring within the first 28 days that is deemed possibly related to the combination regimen, unless the toxicity is clearly attributable to a single non-XB2001 component. Specific DLT criteria include: 1. Inability to deliver all scheduled doses during the 28-day window due to unexpected drug-related toxicity. 2. Inability to deliver the intended dose of XB2001 due to drug-related toxicity.

  28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).

• Safety and Tolerability of XB2001 in Combination With ONIVYDE + LV + 5-FU

  This endpoint evaluates the cumulative safety profile and patient tolerance of XB2001 when administered at the Maximum Tolerated Dose (MTD) or the maximum dose studied in Phase I, in combination with the ONIVYDE + LV + 5-FU regimen. Safety is characterized by the total number of participants in each cohort who experienced one or more adverse events. For the purpose of this count, each participant is counted only once, regardless of the total number of individual adverse events experienced.

  From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.

Secondary Outcomes (9)

• Progression Free Survival (PFS)

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

• Overall Survival (OS)

  From baseline until death from any cause

• Objective Response Rate (ORR)

  Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.

• Time to Treatment Failure(TTF)

  From baseline until treatment failure assessed up to Visit 13 (Week 24)

• Number of Serious Adverse Events (SAEs)

  From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.

Study Arms (2)

Phase I: Dose Escalation Phase

EXPERIMENTAL

In Phase I (Dose escalation phase), 3 sequential dose levels were administered by participants; 250 mg (dose cohort 1), 500 mg (dose cohort 2), and 1000 mg (dose cohort 3), and traditional 3:3 design was used. Dose-escalation will continue if none of three subjects experience a dose-limiting toxicity (DLT). After enrollment participants received two treatment cycles (a total of 28 days) in which they were given one intravenous (IV) dose of XB2001 prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Biological: Phase I: XB2001 250 mg; Biological: Phase I: XB2001 500 mg; Biological: Phase I: XB2001 1000 mg

Phase II: Dose Expansion Phase

EXPERIMENTAL

In Phase II (dose expansion phase), participants were randomized in 1:1 fashion and received: 1. XB2001 1000 mg combination with ONIVYDE, Leucovorin, and 5-Fluorouracil 2. Placebo 1000 mg in combination with ONIVYDE, Leucovorin, and 5-Fluorouracil

Biological: Phase II: XB2001 1000 mg; Biological: Phase II: Placebo

Interventions

Phase II: Placebo BIOLOGICAL

Subjects were administered one intravenous (IV) dose of placebo 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Phase II: Dose Expansion Phase

Phase I: XB2001 500 mg BIOLOGICAL

Subjects were administered one intravenous (IV) dose of XB2001 500 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Also known as: anti-IL-1⍺ True Human antibody

Phase I: Dose Escalation Phase

Phase II: XB2001 1000 mg BIOLOGICAL

Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Also known as: anti-IL-1⍺ True Human antibody

Phase II: Dose Expansion Phase

Phase I: XB2001 250 mg BIOLOGICAL

Subjects were administered one intravenous (IV) dose of XB2001 250 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Also known as: anti-IL-1⍺ True Human antibody

Phase I: Dose Escalation Phase

Phase I: XB2001 1000 mg BIOLOGICAL

Subjects were administered one intravenous (IV) dose of XB2001 1000 mg prior to receiving ONIVYDE 70 mg/m2 IV over 90 minutes, followed by leucovorin 400 mg/m2 IV over 30 minutes, followed by 5-Fluorouracil 2400 mg/m2 intravenously over 46 hours at each cycle.

Also known as: anti-IL-1⍺ True Human antibody

Phase I: Dose Escalation Phase

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 (30)

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

Cleveland Clinic of Florida

Weston, Florida, 33331, 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

Texas Oncology - Arlington

Arlington, Texas, 76012, 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

Results Point of Contact

• Title: XBiotech Clinical
• Organization: XBiotech USA Inc

Clinicaltrials@xbiotech.com

512-386-2900

Study Officials

• David J Park

  Providence St. Joseph Heritage

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: SEQUENTIAL
• 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: August 4, 2026
• Results First Posted: August 4, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (30)