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).
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).
Brief Title
XB2001 in Combination With ONIVYDE + 5-FU/LV (+Folinic Acid) in Advanced Pancreatic Cancer
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: 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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Pancreatic Cancer
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.
* 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.
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04825288
Org Class
Industry
Org Full Name
XBiotech, Inc.
Org Study Id
2020-PT049
Overall Status
Active, not recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Primary Endpoint for Phase I portion
Outcome 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.
Outcome Time Frame
44 days
Outcome Description
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.
Outcome Measure
Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0
Outcome Time Frame
28 weeks
Secondary Outcomes
Outcome 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.
Outcome 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.
Outcome Measure
Progression Free Survival
Outcome 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.
Outcome Time Frame
From baseline until the date of death (from any cause) assessed up to 24 weeks.
Outcome Measure
Overall Survival (OS)
Outcome 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).
Outcome Time Frame
Assessment every 8 weeks after initial response assessed up to 24 weeks.
Outcome Measure
Objective Response Rate
Outcome 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.
Outcome Time Frame
From baseline to treatment discontinuation (any cause) assessed up to 24 weeks
Outcome Measure
Time to Treatment Failure
Outcome 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
Outcome 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
Outcome Measure
Percentage of Patients with Clinical Benefit Response
Outcome Description
Score ranges from 0 to 100. A high score represents a higher response level.
Outcome Time Frame
Baseline to weeks 8, 16 and 24
Outcome Measure
Quality of Life assessed through the cancer-specific European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (QLQ)-C30
Outcome Description
For Phase 2 portion only
Outcome Time Frame
From baseline (Visit 1) (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks
Outcome Measure
Number of Serious Adverse Events (SAEs)
Outcome Description
For Phase 2 portion only
Outcome Time Frame
From Visit 1 (post-infusion) until two weeks after the last infusion, assessed up to 24 weeks
Outcome Measure
Incidence of Grade 3-4 Diarrhea
Outcome Description
For Phase 2 portion only
Outcome Time Frame
Baseline to weeks 4, 8, 12, 16, 20 and 24
Outcome Measure
Duration of hospitalizations
Outcome Description
Plasma/serum concentration of XB2001 will be measured throughout the study.
Outcome Time Frame
At the specified timepoints in the study calendar assessed up to 24 weeks
Outcome Measure
Plasma/serum concentration of XB2001
Outcome Description
For Phase 2 portion only
Outcome Time Frame
Throughout the study assessed up to 24 weeks
Outcome Measure
Number of Treatment Cycles
Outcome Description
For Phase 2 portion only
Outcome Time Frame
Baseline to week 2 (post infusion at visit 2)
Outcome Measure
Change in (CD14+CD16+IL-1⍺+) triple positive tumor associated monocytes in peripheral blood
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Eric Feldman
Investigator Email
efeldman@montefiore.org