XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer (1-BETTER)

July 9, 2026 updated by: XBiotech, Inc.

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

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.

Study Type

Interventional

Enrollment (Actual)

76

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85711
        • Arizona Oncology Associates
    • California
      • Burbank, California, United States, 91505
        • Disney Family Cancer Center at Providence St. Joseph Medical Center
      • Cerritos, California, United States, 90703
        • TOI Clinical Research
      • Fullerton, California, United States, 92835
        • Providence St. Joseph Heritage - Fullerton, CA
      • Newport Beach, California, United States, 92663
        • Hoag Memorial Hospital Presbyterian
    • Colorado
      • Grand Junction, Colorado, United States, 81505
        • Grand Valley Oncology
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Sarah Cannon - Florida Cancer Specialists
      • Miami Beach, Florida, United States, 33140
        • Mt. Sinai Comprehensive Cancer Center
      • Sarasota, Florida, United States, 34239
        • Sarasota Memorial Hospital
      • Weston, Florida, United States, 33331
        • Cleveland Clinic of Florida
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care
    • Kansas
      • Merriam, Kansas, United States, 66204
        • Alliance for Multispecialty Research, LLC
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • Ochsner Clinic Foundation
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute
      • Farmington Hills, Michigan, United States, 48334
        • Revive Research - Farmington Hills
      • Sterling Heights, Michigan, United States, 48126
        • Revive Research - Sterling Heights
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Frontier Cancer Center
    • New Jersey
      • Florham Park, New Jersey, United States, 07932
        • Summit Medical Group
    • New York
      • Stony Brook, New York, United States, 11794
        • Stony Brook Cancer Center
      • The Bronx, New York, United States, 10461
        • Montefiore Einstein Medical Center
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • UPMC Hillman Cancer Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center Cancer Institute
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon - Tennessee Oncology
    • Texas
      • Arlington, Texas, United States, 76012
        • Texas Oncology - Arlington
      • Dallas, Texas, United States, 75230
        • Mary Crowley Cancer Research
    • Utah
      • Ogden, Utah, United States, 84405
        • Community Cancer Trials of Utah
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists
      • Midlothian, Virginia, United States, 23114
        • Bon Secours St. Francis Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase I: Dose Escalation Phase

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
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.
Other Names:
  • anti-IL-1⍺ True Human antibody
Biological: Phase I: XB2001 500 mg
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.
Other Names:
  • anti-IL-1⍺ True Human antibody
Biological: Phase I: XB2001 1000 mg
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.
Other Names:
  • anti-IL-1⍺ True Human antibody
Experimental: Phase II: Dose Expansion Phase

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
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.
Other Names:
  • anti-IL-1⍺ True Human antibody
Biological: Phase II: Placebo
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 28 days (consisting of the first two 14-day treatment cycles or the formal DLT observation window).

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

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
Progression free survival (PFS) was defined as the time from randomization to first progression based on RECIST v1.1 criteria or death from any cause, whichever occurred first. Subjects who had no baseline and post-baseline tumor assessment and no death, or no adequate post-baseline tumor assessment and no death were censored at the date of randomization. Subjects alive and without documented disease progression at the time of data analysis are censored at the date of the last adequate tumor assessment.
From baseline until the date of first documented disease progression or date of death (from any cause), whichever come first.
Overall Survival (OS)
Time Frame: From baseline until death from any cause
OS was defined as the duration from the date of randomization until death irrespective of the cause. Subjects who were alive at the time of analysis were censored at the last known date alive. Subjects without any data after baseline were censored on the randomization day.
From baseline until death from any cause
Objective Response Rate (ORR)
Time Frame: Analyses performed at Visit 5 (Week 8), Visit 9 (Week 16), and Visit 13 (Week 24). This outcome measure was reported for Visit 13.
Objective Response Rate (ORR) is defined as the proportion of subjects in the Phase II Population who achieved a Best Overall Response (BOR) of either Complete Response (CR) or Partial Response (PR), as defined by RECIST v1.1 criteria.
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)
Time Frame: From baseline until treatment failure assessed up to Visit 13 (Week 24)
TTF measures the time from randomization to discontinuation of treatment for any reason, including, but not limited to, disease progression, treatment-related toxicity, and/or death during study.
From baseline until treatment failure assessed up to Visit 13 (Week 24)
Number of Serious Adverse Events (SAEs)
Time Frame: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This outcome measure calculates the total number of unique participants who reported serious adverse events (SAEs) in each group. An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Incidence of Grade 3-4 Diarrhea
Time Frame: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This measure tracks the overall burden of severe (Grade 3) or life-threatening (Grade 4) diarrhea as defined by the NCI CTCAE v5.0. Grade 3 events are severe enough to require medical intervention or significantly limit a person's ability to care for themselves, while Grade 4 events represent urgent, life-threatening clinical situations.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Duration of Hospitalization
Time Frame: From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
This outcome measure calculates the sum of duration of hospitalizations during the study period in phase II population for both groups.
From post-infusion visit 1(week 0) through visit 13 (week 24), which is two weeks after the last infusion.
Plasma Concentration of Natrunix
Time Frame: Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.

Measurement of the concentration of Natrunix in plasma samples to evaluate the pharmacokinetic profile.

Due to reporting limitations on this portal, results from only one time point are reported here.

For Phase 1, samples were collected at V1 pre-dose, V1 post-dose, V2 pre-dose, V3 follow up. For phase 2, samples were collected at V1 pre-dose, V1 post-dose, V1 Day 4, V1 Day 7, V2 pre-dose, V3 pre-dose, V4 pre-dose, V6 pre-dose, V8 pre-dose, and V13 follow up. Placebo patients were tested at V1 post-dose only for verification.
Reported results Natrunix: Phase I: V1 post-dose collected at 30 min post-infusion at visit 1(Week 0), which represents Cmax of Cycle 1. Phase II: V6 pre-dose, at Visit 6 (Week 10), represents the trough of steady state concentration.
Number of Treatment Cycles
Time Frame: From randomization to end of study or study discontinuation for any reasons, up to 24 weeks
This measures the total number of cycles (total number of doses) received by subjects after randomization in each arm.
From randomization to end of study or study discontinuation for any reasons, up to 24 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Results of a symptom questionnaire will be summarized by treatment arm at various post-infusion time points and compared over time
Time Frame: At various post-infusion time points assessed up to 22 weeks
Score ranges from 12 to 48. A high score represents worse outcome.
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
Time Frame: Compared over time, assessed up to 22 weeks
Exploratory Endpoint (Phase 2 portion only)
Compared over time, assessed up to 22 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

XBiotech, Inc.

Investigators

  • Study Chair: David J Park, Providence St. Joseph Heritage

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 27, 2021

Primary Completion (Actual)

October 26, 2023

Study Completion (Actual)

June 10, 2025

Study Registration Dates

First Submitted

March 24, 2021

First Submitted That Met QC Criteria

March 27, 2021

First Posted (Actual)

April 1, 2021

Study Record Updates

Last Update Posted (Actual)

August 4, 2026

Last Update Submitted That Met QC Criteria

July 9, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2020-PT049

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

No plan to share

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe