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

XBiotech

Status and phase: Completed; Phase 2; Phase 1

Conditions: Pancreatic Cancer

Treatments: Biological: XB2001 or Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04825288

2020-PT049

Details and patient eligibility

About

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).

Full 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.

Enrollment: 76 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

76 participants in 2 patient groups, including a placebo group

Arm 1

Active Comparator group

Description:

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).

Treatment:

Biological: XB2001 or Placebo

Arm 2

Placebo Comparator group

Description:

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).

Treatment:

Biological: XB2001 or Placebo