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

Pancreatic Cancer Clinical Trial

— 1-BETTER  

Official 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04825288
• Other study ID #: 2020-PT049
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 27, 2021
• Est. completion date: May 10, 2024

Study information

• Verified date: January 2023
• Source: XBiotech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 69
• Est. completion date: May 10, 2024
• Est. primary completion date: February 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Biological:
• XB2001 or Placebo
XB2001 is a True Human monoclonal antibody that blocks the biological activity of IL-1a 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.

Locations

Country	Name	City	State
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Montefiore Einstein Medical Center	Bronx	New York
United States	Disney Family Cancer Center at Providence St. Joseph Medical Center	Burbank	California
United States	TOI Clinical Research	Cerritos	California
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Revive Research - Farmington Hills	Farmington Hills	Michigan
United States	Summit Medical Group	Florham Park	New Jersey
United States	Providence St. Joseph Heritage - Fullerton, CA	Fullerton	California
United States	Goshen Center for Cancer Care	Goshen	Indiana
United States	Grand Valley Oncology	Grand Junction	Colorado
United States	University of Tennessee Medical Center Cancer Institute	Knoxville	Tennessee
United States	Sarah Cannon - Florida Cancer Specialists	Lake Mary	Florida
United States	Alliance for Multispecialty Research, LLC	Merriam	Kansas
United States	Mt. Sinai Comprehensive Cancer Center	Miami Beach	Florida
United States	Bon Secours St. Francis Cancer Center	Midlothian	Virginia
United States	Sarah Cannon - Tennessee Oncology	Nashville	Tennessee
United States	Vanderbilt University	Nashville	Tennessee
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Hoag Memorial Hospital Presbyterian	Newport Beach	California
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Providence Portland	Portland	Oregon
United States	Sarasota Memorial Hospital	Sarasota	Florida
United States	Revive Research - Sterling Heights	Sterling Heights	Michigan
United States	Stony Brook Cancer Center	Stony Brook	New York
United States	Arizona Oncology Associates	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
XBiotech, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Results of a symptom questionnaire will be summarized by treatment arm at various post-infusion time points and compared over time	Score ranges from 12 to 48. A high score represents worse outcome.	At various post-infusion time points assessed up to 22 weeks
Other	Cardiotoxicity measured by the number of required ECGs and cardiotoxicity related events summarized by treatment arm and compared over time	Exploratory Endpoint (Phase 2 portion only)	Compared over time, assessed up to 22 weeks
Primary	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
Primary	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	Progression Free Survival	Progression Free Survival will be evaluated following the formal database lock, or during an interim analysis, if applicable. PFS is defined as the time from date of randomization to the date of disease progression or death (any cause). Disease progression can include clinical progression, in which it is deemed by the investigator that the patient is coming off study due to the progression of underlying disease. Clinical or radiological (RECIST 1.1) progression will suffice as disease progression.	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.
Secondary	Overall Survival (OS)	Overall survival (OS) will be defined as the duration from the date of randomization until death. Subjects who are alive at the end of follow-up will be censored and survival time will be defined as time from randomization to censor date.	From baseline until the date of death (from any cause) assessed up to 24 weeks.
Secondary	Objective Response Rate	Objective Response Rate will be defined by the percent of patients in the study with a best overall response of CR or PR as assessed by the investigator (per RECIST 1.1).	Assessment every 8 weeks after initial response assessed up to 24 weeks.
Secondary	Time to Treatment Failure	Time to treatment failure is defined as a composite endpoint measuring time from randomization to discontinuation of treatment for any reason, including disease progression, treatment toxicity, or death.	From baseline to treatment discontinuation (any cause) assessed up to 24 weeks
Secondary	Percentage of Patients with Clinical Benefit Response	For Phase 2 portion only. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level. The CBR will be defined as a stabilization or positive (=0 kg) change in lean body mass (LBM)-as assessed by dual-energy X-ray absorptiometry (DEXA) scan, and improvement or no worsening (=0 score point change) on any two of the three symptom scale measures (fatigue, pain, appetite) of EORTC QLQ-C30	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
Secondary	Quality of Life assessed through the cancer-specific European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)-C30	Score ranges from 0 to 100. A high score represents a higher response level.	Baseline to weeks 8, 16 and 24
Secondary	Number of Serious Adverse Events (SAEs)	For Phase 2 portion only	From baseline (Visit 1) (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks
Secondary	Incidence of Grade 3-4 Diarrhea	For Phase 2 portion only	From Visit 1 (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks
Secondary	Duration of hospitalizations	For Phase 2 portion only	Baseline to weeks 4, 8, 12, 16, 20 and 24
Secondary	Plasma/serum concentration of XB2001	Plasma/serum concentration of XB2001 will be measured throughout the study.	At the specified timepoints in the study calendar assessed up to 24 weeks
Secondary	Number of Treatment Cycles	For Phase 2 portion only	Throughout the study assessed up to 24 weeks
Secondary	Change in (CD14+CD16+IL-1?+) triple positive tumor associated monocytes in peripheral blood	For Phase 2 portion only	Baseline to week 2 (post infusion at visit 2)