18.06.2024 17:35:22 - dpa-AFX: GNW-Adhoc: XBiotech Results from Randomized Double-Blinded Phase 1/2 Study Suggest Potential Breakthrough Treatment for Advanced Pancreatic Cancer
AUSTIN, Texas, June 18, 2024 (GLOBE NEWSWIRE) -- XBiotech (NASDAQ: XBIT)
announced today data from its Phase 1/Phase 2 randomized, double-blind, placebo-
controlled multi-center study for advanced pancreatic cancer. Known as 1-BETTER,
the study examined Natrunix (anti-interleukin-1alpha) antibody in combination
with an established chemotherapy regimen (ONIVYDE (ON) + 5-Fluorouracil (5FU) +
Leucovorin (LV), a regimen that is already widely used for treating pancreatic
cancer but is associated with difficult toxicities and less then ideal survival
outcomes. Natrunix was being evaluated as an anti-cancer agent for use in
cytotoxic chemotherapy combinations where the Company believes it might
potentially also improve tolerability of the chemotherapy.
The Phase 1 portion was a dose escalation study in metastatic pancreatic cancer
patients to determine if dose limiting toxicities (DLTs) occurred in combination
with the ON+5FU+LV regimen in second- or third-line setting. DLTs were not
expected with Natrunix and none were seen. The Natrunix dose in the Phase 2
portion was thus the highest dose used in the Phase 1 portion.
Sixty-five subjects were randomized into the Phase 2 study on a 1:1 basis to
receive either Natrunix+ ON+5FU+LV (Arm1) or Placebo +ON+5FU+LV (Arm2). There
were 33 subjects enrolled into Arm1 and 32 into Arm2. The Phase 2 treatment
period was 24-weeks with subjects receiving therapy once every other week for a
total of 12 cycles.
Subjects included in the study had confirmed metastatic, unresectable, or
recurrent pancreatic adenocarcinoma of exocrine pancreas and were required to
have had disease progression after one prior gemcitabine-based therapy or one
FOLFIRINOX and gemcitabine containing therapy. All patients were required to
have at least one measurable lesion according to Response Evaluation Criteria in
Solid Tumor (RECIST v1.1).
The primary endpoint for the Phase 2 study was to assess the safety and
tolerability of Natrunix when used with the ON+5FU+LV combination. Overall,
there were fewer adverse events (AEs) of any kind during the 24-week treatment
period for the Natrunix arm compared to placebo (297 vs 336), with markedly
fewer events in specific categories of adverse events during that time. There
was a 28% reduction in the number of subjects experiencing significant adverse
events (SAEs) in the Natrunix arm (9 out of 33) versus placebo (12 out of 32)
that occurred during the 24-week treatment period. Subjects receiving the
Natrunix ON+5FU+LV regimen also had about a 33% reduction in hospitalization (80
days versus 120 days) during the 24-week treatment period compared to subjects
receiving placebo + ON+5FU+LV combination.
Subjects receiving the Natrunix combination also reported a 22% reduction in
fatigue (28 vs 36), 32% improved appetite (19 vs 28) and 41% reduction in pain
(17 vs 29) as of the last day of the 24-week treatment period compared to
subjects receiving the placebo ON+5FU+LV combination.
Severe diarrhea that can be life -threatening is a significant complication for
the ON+5FU+LV regimen. There was a two-fold reduction (9% versus 19%) in the
incidence of severe diarrhea during the 24-week treatment regimen for patients
receiving the Natrunix + ON+5FU+LV combination compared to placebo + ON+5FU+LV.
Overall Survival (OS), one of the secondary endpoints for the Phase 2 study, was
conventionally defined in as time from randomization to death. The sample size
for the study included intent-to-treat analysis of 33 subjects randomized into
the Natrunix + ON+5FU+LV arm versus 32 subjects in Placebo + ON+5FU+LV arm. A
Kaplan-Meier Survival Curve using a product limit comparison method was
performed. This data highlights the observation that no subjects in the placebo
ON+5FU+LV group (n=32) survived for longer than 330 days, whereas 8 subjects in
the Natrunix ON+5FU+LV arm (n=33) were still alive as of day 330. Considering
the small sample size, the borderline statistically significant p-value of p =
0.096 suggests prolonged survival for subjects receiving the Natrunix regimen.
The lead investigator for the study, David J. Park, MD Medical Oncologist,
Medical Director for the providence St. Jude Crosson Institute, Fullerton, CA
stated "Treatment of advanced pancreatic cancer in the second and third line
settings presents significant challenges in terms of toxicity as well as
efficacy. To observe these trends for reduced toxicity and potential survival
benefit is remarkable, particularly given the limited sample size. The
potential interaction between reduced toxicity, more time on treatment and
improvement in survival makes intuitive sense for clinicians who treat these
patients. These findings are extremely important."
While there was a relatively small number of pancreatic cancer patients enrolled
in the Phase 2 portion of the study, in the Company's opinion, the findings show
better outcomes for the Natrunix + ON+5FU+LV group as compared to the control
arm. The Company believes that the reduced number of serious and adverse events,
the significant reduction in hospitalization, and improved OS during the
respective time periods described above for each of these metrics suggest that
Natrunix could represent a breakthrough advance for the treatment of pancreatic
cancer.
About XBiotech
XBiotech is pioneering the discovery and development of targeted antibodies
based on its True Human(TM) technology. The company's mission is to rethink the way
antibody medicines are discovered and commercialized by advancing its robust
pipeline of truly natural human antibodies for treating serious diseases such as
inflammatory conditions like rheumatology, infectious disease, cardiovascular
disease and cancer. XBiotech has several candidate products including Natrunix.
Cloned from individual donors who possess natural immunity against certain
targeted diseases, XBiotech's pipeline of True Human antibodies are intended to
deliver unmatched safety and efficacy. Located just minutes from downtown
Austin, the XBiotech campus headquarters includes GMP manufacturing facilities,
research and testing laboratories, infectious disease research facilities, and
quality control and clinical operations. For more information, visit
www.xbiotech.com (http://www.xbiotech.com).
Cautionary Note on Forward-Looking Statements and Study Results
This press release contains forward-looking statements, including declarations
regarding management's beliefs and expectations that involve substantial risks
and uncertainties. Forward-looking statements are subject to inherent risks and
uncertainties in predicting future results and conditions that could cause the
actual results to differ materially from those projected in these forward-
looking statements. These risks and uncertainties are subject to the disclosures
set forth in the "Risk Factors" section of certain of our SEC filings. Any
forward-looking statements that we make in this press release speak only as of
the date of this press release. We assume no obligation to update our forward-
looking statements whether as a result of new information, future events or
otherwise, after the date of this press release. The Company makes no
representations regarding OS or any other metric beyond the time periods
specifically discussed herein. There can be no assurance that any study results
discussed in this press release will be replicated in future studies or that
Natrunix will be approved by the Food and Drug Administration or any other
regulator.
Contact
Wenyi Wei
wwei@xbiotech.com
(https://www.globenewswire.com/Tracker?data=Au6eDChPGajVNDblNhH6fQgudOcnFejtWYer
4pR4TX9dIxYJOqUpLjj1b7Q-xNJfCQbjJiBQqd88HlK62MA9yxgXF8OEgog_FaXp-XBbjAY=)
Tel. 737-207-4600
A photo accompanying this announcement is available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/7a17b3d3-b304-47ae-b1e7-
0950f0301f12
Â