Zanidatamab demonstrated a median
overall survival (OS) of 15.5 months in patients with centrally
confirmed immunohistochemistry (IHC) 2+ or 3+ and a median OS of
18.1 months in patients with IHC 3+ tumors
With approximately two years of median
follow-up, as of July 28, 2023,
median duration of response (DOR) increased by two months from
initial analysis to 14.9 months
DUBLIN, June 1, 2024
/PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ)
today announced long-term follow-up results, including the
first-ever overall survival (OS) findings, from the Phase
2b HERIZON-BTC-01 clinical trial of
zanidatamab in previously treated, unresectable, locally advanced,
or metastatic HER2-positive biliary tract cancer (BTC). These
data will be featured at the American Society of Clinical Oncology
(ASCO) Annual Meeting in a poster presentation during the
Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and
Hepatobiliary session on June 1,
2024, at 1:30-4:30 p.m.
CDT. Zanidatamab is a human epidermal growth factor
receptor 2 (HER2)-targeted bispecific antibody being studied in
multiple solid tumors.
For the trial's primary endpoint, results demonstrated that a
confirmed objective response rate (cORR) by independent central
review (ICR) was maintained at 41.3% (95% confidence
interval (CI): 30.4, 52.8) and one additional patient achieved a
complete response (n=2; 2.5%) since initial findings were presented
at the ASCO Annual Meeting in 2023. The median duration of response
(DoR), one of the trial's key secondary endpoints, increased by
approximately 2 months to 14.9 months (95% CI: 7.4, not reached),
compared to the previously reported findings. In this data cut,
zanidatamab demonstrated a median estimated OS, another secondary
endpoint, of 15.5 months (95% CI: 10.4, 18.5) in all patients with
HER2+ BTC, 18.1 months (95% CI:12.2, 23.2) in patients with IHC 3+
tumors, and 5.2 months (95% CI: 3.1, 10.2) in patients with IHC 2+
tumors. Results highlight the clinically meaningful benefits of
sustained and durable responses with continued treatment with
zanidatamab.
"Patients with BTC are typically diagnosed when their disease is
at an advanced stage, which is associated with a poor prognosis,"
said Shubham Pant, M.D., M.B.B.S. professor in the Department of
Gastrointestinal Medical Oncology and Investigational Cancer
Therapeutics at The University of Texas
MD Anderson Cancer Center. "Historically, overall survival with
standard-of-care chemotherapy in second-line patients with advanced
BTC is reported to be between 6-9 months1 so there
is a significant unmet need for targeted therapies that can
potentially improve survival. The deep and durable responses seen
in this study signal the potential to fill a critical unmet patient
need with zanidatamab, a chemotherapy-free option, among patients
with HER2-expressing cancers."
"We are encouraged by the updated results from the pivotal
HERIZON-BTC-01 trial demonstrating sustained clinical activity in
previously treated patients with advanced HER2-positive BTC.
Results from HERIZON-BTC-01 were included in the Biologics License
Application (BLA) for zanidatamab, which was granted Priority
Review by the FDA earlier this week, as well as in the Marketing
Authorization Application for zanidatamab which was recently
submitted to the European Medicines Agency," said Rob Iannone, M.D., M.S.C.E., executive vice
president, global head of research and development of Jazz
Pharmaceuticals. "Clinical development of zanidatamab for the
treatment of advanced HER2-positive BTC continues with
HERIZON-BTC-302 (NCT06282575), the ongoing, global, randomized
Phase 3 trial of zanidatamab in combination with standard-of-care
therapy in the first-line setting for patients with HER2-positive
BTC. We also look forward to investigating zanidatamab's potential
in other HER2-expressing solid tumors, including in cases resistant
to prior HER2-targeted therapies."
Trial Results
Results from this long-term analysis of the Phase 2b HERIZON-BTC-01 trial
(NCT04466891) indicate that zanidatamab monotherapy
demonstrated sustained and durable antitumor responses in
previously treated patients with HER2-positive unresectable,
locally advanced, or metastatic BTC and support the clinically
meaningful benefit of continued treatment with zanidatamab. The
safety profile in all enrolled patients remained manageable with
favorable tolerability compared with the initial analysis. Two
(2.3%) patients discontinued treatment due to treatment-related
adverse events (TRAEs).
The trial evaluated zanidatamab (20 mg/kg IV once every 2 weeks)
in patients with HER2-positive, locally advanced unresectable, or
metastatic BTC who had received prior gemcitabine-containing
therapy. Patients with prior HER2-targeted therapy use were
excluded from the trial. All patients were required to have
centrally confirmed HER2-amplified tumors (assessed by in
situ hybridization). Patients (n=87) were assigned into two
cohorts based on tumor IHC status: Cohort 1 (n=80) included
patients who were IHC 2+/3+ (HER2-positive) and Cohort 2 (n=7)
included patients who were IHC 0/1+. The median duration of
follow-up was 21.9 (16-34) months. Tumors were assessed every 8
weeks per RECIST v1.1. Updated efficacy analyses include only
Cohort 1, while safety analyses include Cohorts 1 and 2.
As of July 28, 2023, data from HER2-positive BTC patients
enrolled in Cohort 1 (n=80) demonstrated:
- With longer follow-up, the cORR was maintained from the initial
analysis (n=33; 41.3%) (95% CI: 30.4, 52.8), with one additional
complete response (n=2; 2.5%).
- Although the trial was not designed to detect treatment effects
by HER2 status, as previously reported, in a pre-planned subgroup
analysis of cORR by HER2 expression, responses were observed in
patients with IHC 3+ tumors (cORR: 51.6% [95% CI: 38.6%-64.5%]) and
IHC 2+ tumors (cORR: 5.6% [95% CI: 0.1-27.3%])2.
- A two-month increase in the median DoR to 14.9 months (95% CI:
7.4, not reached).
- In patients with IHC3+ tumors, the median DoR was 14.9 months
(95% CI: 7.4, not reached).
- The DOR in the 1 responder with IHC 2+ tumors was 7.5
months.
- A median OS (95% CI) of 15.5 months (95% CI: 10.4, 18.5).
- The median OS in patients with IHC 3+ was 18.1 months (95% CI:
12.2, 23.2).
- The median OS in patients with IHC 2+ was 5.2 months (95% CI:
3.1, 10.2).
- Median progression-free survival (PFS) was maintained (5.5
months [95% CI: 3.6, 7.3]) compared with the initial analysis,
which had a data cutoff of October 10,
2022.
- In patients with IHC 3+ tumors, the median PFS was 7.2
months (95% CI: 5.4, 9.4) months.
- In patients with IHC 2+ tumors, the median PFS was 1.7
months (95% CI: 1.0, 3.3) months.
As previously reported for Cohorts 1 and 2, zanidatamab
demonstrated a manageable and tolerable safety profile, with no new
safety signals identified and no deaths that were treatment
related. TRAEs leading to dose reductions remained infrequent.
Serious TRAEs occurred in eight (9.2%) patients. One patient
experienced serious TRAEs since the initial analysis (alanine
aminotransferase increased and aspartate aminotransferase
increased).Treatment discontinuation rate was 2.3% and no
additional patients discontinued treatment due to TRAEs since the
initial analysis.
About BTC
BTC, including gallbladder cancer and
intrahepatic and extrahepatic cholangiocarcinoma, account for
<1% of all adult cancers globally and are often associated with
a poor prognosis.3,4 The human epidermal growth
factor receptor 2 (HER2) is a well-validated target for antitumor
therapy in other cancers. Across the U.S., Europe, and Japan, approximately 12,000 people are
diagnosed with HER2+ BTC annually.5,6,7,8
About Zanidatamab
Zanidatamab is an investigational HER2-targeted bispecific antibody
that can simultaneously bind two non-overlapping epitopes of the
HER2 receptor, known as biparatopic binding. This unique design and
increased binding results in multiple mechanisms of action,
including dual HER2 signal blockade, removal of HER2 protein from
the cell surface, and immune-mediated cytotoxicity leading to
encouraging antitumor activity in patients. 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 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
to fill a persistent and much-needed treatment gap, growing our
portfolio of innovative oncology products and investigational
therapies, advancing our broader clinical development program
for zanidatamab 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 Strategic Brand Engagement
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 Yoo C, Kim KP, Jeong JH,
Kim I, Kang MJ, Cheon J, Kang BW, Ryu H, Lee JS, Kim KW, Abou-Alfa
GK, Ryoo BY. Liposomal irinotecan plus fluorouracil and leucovorin
versus fluorouracil and leucovorin for metastatic biliary tract
cancer after progression on gemcitabine plus cisplatin (NIFTY): a
multicentre, open-label, randomised, phase 2b study. Lancet Oncol. 2021
Nov;22(11):1560-1572. doi: 10.1016/S1470-2045(21)00486-1. Epub 2021
Oct 14. PMID: 34656226.
2 Harding, J. J., Fan, J., Oh, D., Hye Jin Choi, Jin Won
Kim, Chang, H.-M., Bao, L., Sun, H., Macarulla, T., Xie, F.,
Jean-Phillippe Metges, Ying, J., Bridgewater, J., Myung Ah Lee, Mohamedtaki Abdulaziz Tejani, Chen, E. Y.,
Dong Uk Kim, Harpreet Wasan, Ducreux, M., & Bao, Y.
(2023). Zanidatamab for HER2-amplified, unresectable, locally
advanced or metastatic biliary tract cancer (HERIZON-BTC-01): a
multicentre, single-arm, phase 2b
study. Lancet Oncology, 24(7), 772–782.
https://doi.org/10.1016/s1470-2045(23)00242-5
3 Valle JW, et al. Lancet 2021; 397:428-44
4 Siegel RL, et al. CA Cancer J Clin 2022;
72;7-33
5 BTC overall diagnosed patients as per SEER 22;
6 Assumes anatomic subsites intrahepatic CCA,
extrahepatic CCA, gallbladder cancer, and BTC unspecified;
7 Assumes HER2 positivity rates per anatomical subsite
from: Galdy, S., Lamarca, A., McNamara, M.G. et al. Cancer
Metastasis Rev 36, 141–157 (2017), Nobuyoshi Hiraoka, et al. Human Pathology,
Volume 105, 2020, Pages 9-19
8 Major markets: U.K, France, Germany, Spain, Italy.
Note: HER2+ BTC patients in Jazz-controlled commercial territories,
which includes Japan, and excludes
other certain Asia Pacific
countries licensed to BeiGene, Ltd
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