XBiotech Results from Randomized Double-Blinded Phase 1/2 Study Suggest Potential Breakthrough Treatment for Advanced Pancreatic Cancer
June 18 2024 - 11:35AM
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 XBiotechXBiotech is
pioneering the discovery and development of targeted antibodies
based on its True Human™ 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.
Cautionary Note on Forward-Looking
Statements and Study ResultsThis 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 Weiwwei@xbiotech.comTel.
737-207-4600
A photo accompanying this announcement is
available at
https://www.globenewswire.com/NewsRoom/AttachmentNg/7a17b3d3-b304-47ae-b1e7-0950f0301f12
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