Phase 2 updated results for zanidatamab in
HER2-positive mGEA included a confirmed objective response rate
(cORR) of 84%, duration of response (DoR) of 18.7 months, median
progression-free survival (mPFS) of 15.2 months and a
Kaplan-Meier–estimated overall survival (OS) of 59%
at 30 months
DUBLIN, Sept. 16,
2024 /PRNewswire/ -- Jazz Pharmaceuticals
plc (Nasdaq: JAZZ) today announced updated data, including
median progression-free survival (mPFS) and overall survival (OS)
findings, from the Phase 2 trial of zanidatamab, an investigational
dual HER2-targeted bispecific antibody, in combination with
chemotherapy as first-line treatment for patients with
HER2-expressing advanced or metastatic gastroesophageal
adenocarcinoma (mGEA).
Data from 41 patients with HER2-positive mGEA who were treated
with zanidatamab in combination with physician's choice of
chemotherapy treatment demonstrated a mPFS of 15.2 [95% CI:
9.5, 33.4] months. After a median duration of follow-up of 41.5
(range, 23.0-52.7) months, the median OS was not mature, a
Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0, 78.0] and
the 30-month overall survival was 59% [95% CI: 41.0, 73.0].
"Gastroesophageal adenocarcinoma (GEA) represents one of the
most common tumor types worldwide; however, developing effective
treatment options for GEA patients has been challenging," said Dr.
Elena Elimova, lead trial investigator and a medical oncologist
at Princess Margaret Cancer Centre, Toronto, Canada. "Despite recent advancements
for patients, the sustained clinical antitumor activity seen in
this trial demonstrates the potential for zanidatamab to address a
significant unmet patient need in HER2-positive GEA."
"The updated results from this Phase 2 trial reaffirm
zanidatamab's potential as a foundational treatment for patients
with HER2-positive mGEA and showcase the promise of this
HER2-targeted bispecific antibody to treat HER2-expressing
cancers," said Rob Iannone, M.D.,
M.S.C.E., executive vice president, global head of research and
development, and chief medical officer of Jazz
Pharmaceuticals. "We look forward to continuing to advance our
broader clinical development program for zanidatamab in GEA,
including the Phase 3 first-line clinical trial HERIZON-GEA-01 that
is expected to read out in the second quarter of 2025, and other
HER2-expressing solid tumors, with the goal of supporting more
patients with HER2-positive cancers."
Phase 2 mGEA Trial Results
The data include efficacy and tolerability findings from an
ongoing, open-label Phase 2 study (NCT03929666) evaluating
zanidatamab in combination with chemotherapy as first-line
treatment for patients with HER2-expressing mGEA, which comprises
gastric, esophageal and gastroesophageal junction (GEJ)
adenocarcinomas. Patients had not received prior HER2-targeted
agents nor systemic treatment for mGEA. A total of 46 patients with
HER2-expressing mGEA (41 patients with HER2-positive mGEA) were
enrolled from 15 sites across the United
States, Canada and South Korea, and patients were
administered zanidatamab with physician's choice of chemotherapy
treatment. Currently, chemotherapy-based regimens are the standard
first-line combination therapy for 1L mGEA.
The longer-term data (median duration of follow-up of 41.5
[range, 23.0-52.7] months) demonstrates the promising antitumor
activity of zanidamatab combined with chemotherapy as a first-line
therapy for HER2-positive mGEA.
- Treatment with zanidatamab resulted in a cORR of 84% [95% CI:
68.0, 94.0], an increase of 5% from the cORR previously reported,
and one additional patient achieved a complete response for a total
of four patients achieving complete response among 37-response
evaluable patients.
- The median duration of response was 18.7 months [95% CI:
8.3-NE] with 10 patients having an ongoing response at the time of
data cutoff.
- The mPFS was 15.2 [95% CI: 9.5, 33.4] months.
- The Kaplan-Meier–estimated 24-month OS was 65% [95% CI: 48.0,
78.0] with a 30-month overall survival of 59% [95% CI: 41.0,
73.0].
With additional follow-up, the safety and tolerability profile
of zanidatamab plus chemotherapy remained manageable with no new
safety signals identified. Diarrhea was the most common Grade 3-4
treatment-related adverse events (TRAEs) (35%); the incidence of
Grade 3-4 diarrhea was <15% for patients treated after the
implementation of mandated antidiarrheal prophylaxis. Treatment
discontinuation due to TRAEs were infrequent, and there were no
treatment-related deaths.
These data were presented in a poster session
entitled Zanidatamab + Chemotherapy for First-Line
Treatment for HER2+ Advanced or Metastatic Gastroesophageal
Adenocarcinoma (mGEA) during the European Society for
Medical Oncology (ESMO) Annual Meeting taking place in Barcelona, Spain. The presentation is
available to conference registrants on the ESMO conference website
(Presentation Number 1423P).
Jazz continues to enroll patients in the Phase 3 randomized
clinical trial, HERIZON-GEA-01 (NCT05152147), evaluating
zanidatamab in combination with chemotherapy plus or minus
tislelizumab as a first-line treatment for HER2-expressing mGEA.
This is an events-based trial; top-line data from this trial is
expected to read out in the second quarter of 2025.
Phase 2 Colorectal Cancer (CRC) Trial Results Presented as
Mini-Oral at ESMO 2024
In addition to the mGEA trial
presentation, a mini-oral was also presented at ESMO 2024 from
another arm of the same Phase 2, open-label trial (NCT03929666)
that includes a cohort of patients with metastatic CRC treated with
first-line zanidatamab plus chemotherapy ± bevacizumab (bev). In 11
response-evaluable patients, there were 10 confirmed partial
responses and 1 patient with stable disease as a best response. The
cORR was 91% (95% CI: 58.7, 99.8) and median duration of response
was not reached (2.9+,16.7+ months). All patients experienced TRAEs
– Grade 3-4 TRAEs occurred in five (38%) patients, three (23%) of
whom experienced diarrhea. No patients discontinued zanidatamab due
to a TRAE and there were no treatment-related deaths. Zanidatamab
plus chemotherapy ± bev demonstrated encouraging antitumor activity
with a generally manageable safety profile as first-line treatment
for patients with HER2-positive mCRC.
About Zanidatamab
Zanidatamab is an investigational dual HER2-targeted bispecific
antibody that simultaneously binds to two distinct sites on HER2,
known as biparatopic binding. This unique design and enhanced
binding results in multiple mechanisms of action, including HER2
and HER3 signal blockade, removal of HER2 protein from the cell
surface and enhanced immune effector functions, such as
complement-dependent cytotoxicity (CDC), which leads to encouraging
antitumor activity. Zanidatamab is being developed in multiple
clinical trials as a targeted treatment option for patients with
solid tumors that express HER2. Zanidatamab is being developed
by Jazz and BeiGene, Ltd. (BeiGene) under license
agreements from Zymeworks, which first developed the molecule.
The U.S. Food and Drug Administration (FDA) has
accepted and granted Priority Review of the Biologics
License Application (BLA) for zanidatamab with a Prescription Drug
User Fee Act (PDUFA) action date of November 29, 2024.
Zanidatamab was also granted Breakthrough Therapy designation in
patients with previously treated HER2 gene-amplified biliary tract
cancers (BTC) and given two Fast Track designations: one as a
single agent for refractory BTC and one in combination with
standard of care chemotherapy for 1L gastroesophageal
adenocarcinoma (GEA). Additionally, zanidatamab has received Orphan
Drug designations from FDA for the treatment of BTC and GEA, as
well as Orphan Drug designation from the European Medicines
Agency for the treatment of BTC and gastric cancer.
Zanidatamab was also granted Breakthrough Therapy designation from
the Center for Drug Evaluation (CDE) in China.
About Gastroesophageal Adenocarcinoma
Gastroesophageal
adenocarcinoma (GEA) is the fifth most common cancer worldwide, and
approximately 20% of patients have HER2–positive
disease.1,2,3 HER2–positive GEA has high morbidity
and mortality, and patients are urgently in need of new treatment
options.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma
company whose purpose is to innovate to transform the lives of
patients and their families. We are dedicated to developing
life-changing medicines for people with serious diseases—often with
limited or no therapeutic options. We have a diverse portfolio of
marketed medicines, including leading therapies for sleep disorders
and epilepsy, and a growing portfolio of cancer treatments. Our
patient-focused and science-driven approach powers pioneering
research and development advancements across our robust pipeline of
innovative therapeutics in oncology and neuroscience. Jazz is
headquartered in Dublin, Ireland with research and
development laboratories, manufacturing facilities and employees in
multiple countries committed to serving patients worldwide. Please
visit www.jazzpharmaceuticals.com for more
information.
Jazz Pharmaceuticals plc Caution Concerning
Forward-Looking Statements
This press release contains forward-looking statements, including,
but not limited to, statements related to zanidatamab's potential
as a foundational treatment for patients with HER2-positive mGEA,
the promise of HER2-targeted bispecific antibodies to treat
HER2-expressing cancers and zanidatamab's potential to address
a significant unmet patient need, growing our portfolio of
innovative oncology products and investigational therapies,
advancing our broader clinical development program for
zanidatamab, including expectations with respect to the timing of
the GEA Phase 3 clinical trial read out and other statements that
are not historical facts. These forward-looking statements are
based on Jazz Pharmaceuticals' current plans, objectives,
estimates, expectations and intentions and inherently involve
significant risks and uncertainties. Actual results and the timing
of events could differ materially from those anticipated in such
forward-looking statements as a result of these risks and
uncertainties, which include, without limitation, risks and
uncertainties associated with pharmaceutical product development,
and other risks and uncertainties affecting Jazz
Pharmaceuticals and its development programs, including those
described from time to time under the caption "Risk Factors" and
elsewhere in Jazz Pharmaceuticals plc's Securities and
Exchange Commission filings and reports (Commission File No.
001-33500), including Jazz Pharmaceuticals' Annual Report
on Form 10-K for the year ended December 31, 2023, as
supplemented by our Quarterly Report on Form 10-Q for the quarter
ended March 31, 2024, and future filings and reports
by Jazz Pharmaceuticals. Other risks and uncertainties of
which Jazz Pharmaceuticals is not currently aware may
also affect Jazz Pharmaceuticals' forward-looking
statements and may cause actual results and the timing of events to
differ materially from those anticipated. The forward-looking
statements herein are made only as of the date hereof or as of the
dates indicated in the forward-looking statements, even if they are
subsequently made available by Jazz Pharmaceuticals on
its website or otherwise. Jazz Pharmaceuticals undertakes
no obligation to update or supplement any forward-looking
statements to reflect actual results, new information, future
events, changes in its expectations or other circumstances that
exist after the date as of which the forward-looking statements
were made.
Contacts:
Jazz Media Contact:
Kristin Bhavnani
Head of Global Corporate Communications
Jazz Pharmaceuticals plc
CorporateAffairsMediaInfo@jazzpharma.com
Ireland +353 1 637 2141
U.S. +1 215 867 4948
Jazz Investor Contact:
Andrea N. Flynn, Ph.D.
Vice President, Head, Investor Relations
Jazz Pharmaceuticals plc
investorinfo@jazzpharma.com
Ireland +353 1 634 3211
U.S. +1 650 496 2717
References:
1 Abrahao-Machado I.F., et al. HER2 testing
in gastric cancer: An update WorldJGastroenterol.
2016;22(19):4619-4625.
2 Van Custem E., et al. HER2 screening data
from ToGA: targeting HER2 in gastric and gastroesophageal junction
cancer. Gastric Cancer. 2015;18(3):476-484.
3 Stroes, C.I., et al. A systematic review of HER2
blockade for the curative treatment of gastroesophageal
adenocarcinoma: Successes achieved and opportunities
ahead. CancerTreatRev. 2021;99:102249.
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