First presentation of progression-free
survival (PFS) primary endpoint data show zanidatamab plus
palbociclib and fulvestrant demonstrated a PFS of 67% at 6 months
and a median PFS of 12 months in patients with heavily pre-treated
HER2+/HR+ metastatic breast cancer (mBC)
Efficacy and safety results support further
investigation of this targeted combination therapy as a potential
chemotherapy-free option for patients with HER2+/HR+ mBC
DUBLIN, Dec. 8, 2023
/PRNewswire/ -- Jazz Pharmaceuticals plc (Nasdaq: JAZZ)
today presented updated data from the Phase 2a trial of
investigational zanidatamab, a HER2-targeted bispecific antibody,
in combination with palbociclib, a CDK4/6 inhibitor, and
fulvestrant, a selective estrogen receptor antagonist, in patients
with HER2-positive (HER2+)/HR-positive (HR+) metastatic breast
cancer (mBC) as part of a late-breaking oral presentation
at the 2023 San Antonio Breast Cancer Symposium (SABCS).
Data from 51 patients with heavily pretreated HER2+/HR+ mBC
(median of 4 prior regimens in the metastatic setting) who were
treated with zanidatamab plus palbociclib and fulvestrant
demonstrated a progression-free survival at six months (PFS6) of
67% (n=34) [95% confidence interval: 52, 79]. Secondary endpoint
findings included a median progression-free survival (mPFS) of 12
months [95% CI: 8, 15] and a confirmed objective response rate
(cORR) of 35% [95% CI: 21, 50] with a median duration of
response (DOR) of 15 months. The combination regimen was well
tolerated with a manageable safety profile.
"Metastatic breast cancer is a particularly aggressive and
devastating disease, and patients whose cancer has progressed
despite numerous therapeutic interventions are in dire need of
additional treatment options – particularly chemotherapy-free
options," 1,2 said Santiago Escrivá-de-Romani, MD,
Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron
University Hospital, and primary trial investigator. "Targeting
both the HER2 and hormone receptor pathways can be a promising
approach for applicable patients, and the durable responses seen in
this study signal the potential for this combination to fill a
persistent and much needed treatment gap among these
patients."3
"The late-breaking data presented at SABCS for zanidatamab in
combination with palbociclib and fulvestrant in HER2+/HR+
metastatic breast cancer as a chemotherapy-free treatment option in
heavily pretreated patients provide yet another example of the
promise this HER2-targeted bispecific antibody holds in the
treatment of HER2-expressing cancers where significant unmet needs
exist," said Rob Iannone, M.D.,
M.S.C.E., executive vice president, global head of research and
development of Jazz Pharmaceuticals. "We are encouraged by the
meaningful clinical benefit seen in this trial, and we look forward
to continuing to advance our broader clinical development program
for zanidatamab in breast cancer and other HER2-expressing solid
tumors, with the goal of addressing some of the greatest unmet
needs in cancer with HER2 expression."
Trial Results
Results of the Phase 2a trial (NCT04224272) presented at SABCS
indicate that zanidatamab in combination with palbociclib and
fulvestrant, demonstrated meaningful PFS outcomes with a well
tolerated safety profile in patients with heavily pretreated
HER2+/HR+ mBC.
The single-arm trial evaluated zanidatamab plus palbociclib and
fulvestrant in 51 patients with HER2+/HR+ unresectable, locally
advanced or metastatic breast cancer who had received prior
treatment with at least trastuzumab, pertuzumab, and T-DM1, and no
prior treatment with a CDK4/6 inhibitor. Patients treated with the
combination regimen received a median of four prior systemic
regimens in the metastatic setting (range, 1-12).
Recommended doses of the zanidatamab plus palbociclib and
fulvestrant combination therapy were determined in Part 1 of the
study. The primary endpoint of Part 2 was PFS6. Other endpoints
included mPFS, cORR per RECIST v1.1, DCR and DOR.
At the time of data cutoff (August 3,
2023), treatment with zanidatamab in combination with
palbociclib and fulvestrant resulted in a PFS6 of 67% (n=34) and
mPFS of 12 months [95% CI: 8, 15]. Median duration of follow-up was
16 months (range, 2-32). Patients treated with the combination
regimen achieved a cORR of 35% and DCR of 91%.
Efficacy
|
All pts
(N=51)
|
PFS6, n (%)
(95% CI)
|
34 (67)
(52-79)
|
Median PFS,
mo
(95% CI)
|
12
(8-15)
|
cORR, n (%)
(95% CI)
|
16 (35)
(21-50)
|
Confirmed best overall
response (cBOR), n (%)
Complete
Response
Partial
response
SD
PD
|
3 (6)
13 (28)
26 (56)
4 (9)
|
DCR, n (%)
(95% CI)
|
42 (91)
(79-98)
|
Median DOR,
mo
(95% CI)
|
15
(12-25)
|
Zanidatamab plus palbociclib and fulvestrant was well tolerated
with a manageable safety profile. One serious treatment-related AE
(transaminases increased) was reported (which resolved). No
treatment-related deaths were reported. The most common
treatment-related AEs (>20% of patients) were diarrhea,
neutrophil count decrease/neutropenia, nausea, stomatitis, anemia,
vomiting and asthenia. One patient discontinued the combination
treatment due to an AE; three patients
discontinued palbociclib due to an AE.
The abstract is available to conference registrants on the SABCS
conference website here. (Abstract Number LBO1-04).
Additional data being presented at SABCS for zanidatamab include
a spotlight poster presentation highlighting positive results of an
investigator-sponsored Phase 1 trial evaluating neoadjuvant
single-agent zanidatamab in patients with stage 1 node-negative
HER2+ breast cancer (Abstract Number PS09-03).
About Zanidatamab
Zanidatamab is an investigational bispecific antibody that can
simultaneously bind two non-overlapping epitopes of HER2, 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
granted Breakthrough Therapy designation for zanidatamab
development in patients with previously treated HER2 gene-amplified
biliary tract cancers (BTC), and two Fast Track designations for
zanidatamab: one as a single agent for refractory BTC and one in
combination with standard of care chemotherapy for first-line
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.
In this Phase 2a trial, zanidatamab is being explored in
combination with palbociclib under a clinical trial and supply
agreement with Pfizer Inc.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global
biopharmaceutical 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 and novel product
candidates, from early- to late-stage development, in neuroscience
and oncology. Within these therapeutic areas, we are identifying
new options for patients by actively exploring small molecules and
biologics, and through innovative delivery technologies and
cannabinoid science. Jazz is headquartered in Dublin,
Ireland and has employees around the globe, serving patients
in nearly 75 countries. Please
visit www.jazzpharmaceuticals.com for more
information.
Caution Concerning Forward-Looking Statements
This press release contains forward-looking statements, including,
but not limited to, statements related to the potential for
zanidatamab in combination with palbociclib and fulvestrant to
fill a persistent treatment gap among metastatic breast cancer
patients 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, 2022, as
supplemented by our Quarterly Report on Form 10-Q for the quarter
ended June 30, 2023, 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:
1Kim M, Lee H, Kim Y, Lee D, Kang S, Jin W. MEST
induces Twist-1-mediated EMT through STAT3 activation in breast
cancers. Cell Death Differ. 2019 Dec;26(12):2594-2606.
2Cancer.org. Treatment of Stage IV (Metastatic) Breast
Cancer.
https://www.cancer.org/cancer/types/breast-cancer/treatment/treatment-of-breast-cancer-by-stage/treatment-of-stage-iv-advanced-breast-cancer.html.
Last accessed January 2023.
3Kay C, Martínez-Pérez C, Meehan J, Gray M, Webber V,
Dixon J, Turnbull A. Current trends
in the treatment of HR+/HER2+ breast cancer. Future Oncol. 2021
May;17(13):1665-1681.
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