Description:
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).
Title
- Brief Title: XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer
- 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 IDs
- ORG STUDY ID:
2020-PT049
- NCT ID:
NCT04825288
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| XB2001 or Placebo | | Arm 1 |
Purpose
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).
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.
Study Chair: Shubham Pant, 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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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). | |
| 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). | |
Eligibility Criteria
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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: | 44 days |
| Safety Issue: | |
| Description: | Primary Endpoint for Phase I portion |
Secondary Outcome Measures
| Measure: | Progression Free Survival |
| Time Frame: | 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. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival (OS) |
| Time Frame: | From baseline until the date of death (from any cause) assessed up to 24 weeks. |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Objective Response Rate |
| Time Frame: | Assessment every 8 weeks after initial response assessed up to 24 weeks. |
| Safety Issue: | |
| Description: | 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). |
| Measure: | Time to Treatment Failure |
| Time Frame: | From baseline to treatment discontinuation (any cause) assessed up to 24 weeks |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Percentage of Patients with Clinical Benefit Response |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Quality of Life assessed through the cancer-specific European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)-C30 |
| Time Frame: | Baseline to weeks 8, 16 and 24 |
| Safety Issue: | |
| Description: | Score ranges from 0 to 100. A high score represents a higher response level. |
| Measure: | Number of Serious Adverse Events (SAEs) |
| Time Frame: | From baseline (Visit 1) (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks |
| Safety Issue: | |
| Description: | For Phase 2 portion only |
| Measure: | Incidence of Grade 3-4 Diarrhea |
| Time Frame: | From Visit 1 (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks |
| Safety Issue: | |
| Description: | For Phase 2 portion only |
| Measure: | Duration of hospitalizations |
| Time Frame: | Baseline to weeks 4, 8, 12, 16, 20 and 24 |
| Safety Issue: | |
| Description: | For Phase 2 portion only |
| Measure: | Plasma/serum concentration of XB2001 |
| Time Frame: | At the specified timepoints in the study calendar assessed up to 24 weeks |
| Safety Issue: | |
| Description: | Plasma/serum concentration of XB2001 will be measured throughout the study. |
| Measure: | Number of Treatment Cycles |
| Time Frame: | Throughout the study assessed up to 24 weeks |
| Safety Issue: | |
| Description: | For Phase 2 portion only |
| Measure: | Change in (CD14+CD16+IL-1⍺+) triple positive tumor associated monocytes in peripheral blood |
| Time Frame: | Baseline to week 2 (post infusion at visit 2) |
| Safety Issue: | |
| Description: | For Phase 2 portion only |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | XBiotech, Inc. |
Last Updated
August 5, 2021
