- New analyses from the pivotal HER2CLIMB trial
describe outcomes by hormone receptor status -
Seagen Inc. (Nasdaq:SGEN) today announced the presentation of
new data from TUKYSA (tucatinib), its HER2-positive metastatic
breast cancer therapy, at the San Antonio Breast Cancer Symposium
(SABCS) Virtual Symposium, taking place December 8-11, 2020. Nine
abstracts – including two spotlight posters – highlight the
company’s commitment to addressing unmet needs in breast
cancer.
“Following this year’s FDA approval of TUKYSA, we continue to
broadly study if more patients may benefit from this important
medicine,” said Roger Dansey, M.D., Chief Medical Officer at
Seagen. “Data presented at the meeting from the HER2CLIMB trial
demonstrate TUKYSA’s efficacy regardless of patients’ hormone
receptor status, while other clinical and preclinical findings
provide new insights about TUKYSA’s potential to help patients
living with HER2-positive metastatic breast cancer.”
Highlights for key data presentations at the meeting
include:
Efficacy Outcomes by Hormone Receptor Status from HER2CLIMB
Trial
Outcomes for TUKYSA® (tucatinib) in combination with trastuzumab
and capecitabine in patients with HER2-positive metastatic breast
cancer from the pivotal HER2CLIMB trial by hormone receptor (HR)
status will be featured in a spotlight poster (Abstract #PD3-08).
Results will be presented by Erika P. Hamilton, M.D., Director,
Breast Cancer and Gynecologic Cancer Research Program at the Sarah
Cannon Research Institute.
As previously reported, the addition of TUKYSA to trastuzumab
and capecitabine resulted in clinically meaningful improvements in
overall survival (OS), progression-free survival (PFS) and
objective response rate (ORR) compared to the addition of placebo.
The new exploratory analyses presented at SABCS demonstrated that
the PFS, OS and ORR improvements with TUKYSA were observed
consistently across hormone receptor status subgroups, including in
patients with brain metastases.
SABCS 2020 Data Presentations for Seagen Medicines and
Pipeline Agents:
Below are presentation details
related to TUKYSA and the investigational agent ladiratuzumab
vedotin at SABCS. Published abstracts can be found here. Poster
presentations will be available on December 9, 2020.
Abstract Title
Abstract No.
Presentation Type / Date
Presenter
Tucatinib versus placebo in combination
with trastuzumab and capecitabine for patients with locally
advanced unresectable or HER2-positive metastatic breast cancer
(HER2CLIMB): outcomes by hormone receptor status
#PD3-08
Spotlight Poster Discussion 3 – Wednesday,
Dec. 9 from 6:45 - 7:45 p.m. CT
E. Hamilton
Impact of tucatinib on health-related
quality of life in patients with HER2+ metastatic breast cancer
with stable and active brain metastases
#PD13-04
Spotlight Poster Discussion 13 – Friday,
Dec. 11 from 1 – 2:15 p.m. CT
A. Wardley
Tucatinib favourably modulates the immune
microenvironment and synergises with anti-PD1 therapy in a
trastuzumab resistant HER2+ murine model
#PS10-04
Poster Session 10 / Wednesday, Dec. 9 at 8
a.m. CT
R. Li
Tucatinib potentiates the activity of the
antibody-drug conjugate T-DM1 in preclinical models of
HER2-positive breast cancer
#PS10-08
Poster Session 10 / Wednesday, Dec. 9 at 8
a.m. CT
A. Kulukian
Real world treatment patterns and
healthcare resource utilization among HER2+ metastatic breast
cancer patients with and without brain metastases: a retrospective
cohort study
#PS14-15
Poster Session 14 / Wednesday, Dec. 9 at 8
a.m. CT
C. Ike
Interim safety and efficacy analysis of
phase IB/II clinical trial of tucatinib, palbociclib and letrozole
in patients with hormone receptor and HER2-positive metastatic
breast cancer
#PS10-03
Poster Session 10 / Wednesday, Dec. 9 at 8
a.m. CT
E. Shagisultanova
Trials-in-Progress
HER2CLIMB-02: A randomized, double-blind,
phase 3 study of tucatinib or placebo with T-DM1 for unresectable
locally-advanced or metastatic HER2+ breast cancer
#OT-28-01
Ongoing Trials Posters / Wednesday, Dec. 9
at 8 a.m. CT
S. Hurvitz
SGNLVA-001: a phase 1 open-label dose
escalation and expansion study of SGN-LIV1A administered weekly in
breast cancer
#OT-03-03
Ongoing Trials Posters / Wednesday, Dec. 9
at 8 a.m. CT
H.C. Beckwith
About TUKYSA (tucatinib)
TUKYSA is an oral medicine that is a tyrosine kinase inhibitor
of the HER2 protein. In vitro (in lab studies), TUKYSA inhibited
phosphorylation of HER2 and HER3, resulting in inhibition of
downstream MAPK and AKT signaling and cell growth (proliferation),
and showed anti-tumor activity in HER2-expressing tumor cells. In
vivo (in living organisms), TUKYSA inhibited the growth of
HER2-expressing tumors. The combination of TUKYSA and the anti-HER2
antibody trastuzumab showed increased anti-tumor activity in vitro
and in vivo compared to either medicine alone. In the U.S., TUKYSA
is approved in combination with trastuzumab and capecitabine for
adult patients with advanced unresectable or metastatic
HER2-positive breast cancer, including patients with brain
metastases (disease that has spread to the brain), who have
received one or more prior anti-HER2-based regimens in the
metastatic setting. TUKYSA is approved in the U.S., Switzerland,
Canada, Singapore and Australia and is under review in the European
Union. As part of a strategic collaboration announced in September
2020 with Merck, known as MSD outside the United States and Canada,
Merck has exclusive rights to commercialize TUKYSA in Asia, the
Middle East and Latin America and other regions outside of the
U.S., Canada and Europe.
U.S. Important Safety Information
Warnings and Precautions
- Diarrhea – TUKYSA can cause severe diarrhea including
dehydration, hypotension, acute kidney injury, and death. In
HER2CLIMB, 81% of patients who received TUKYSA experienced
diarrhea, including 12% with Grade 3 diarrhea and 0.5% with Grade 4
diarrhea. Both patients who developed Grade 4 diarrhea subsequently
died, with diarrhea as a contributor to death. The median time to
onset of the first episode of diarrhea was 12 days and the median
time to resolution was 8 days. Diarrhea led to dose reductions of
TUKYSA in 6% of patients and discontinuation of TUKYSA in 1% of
patients. Prophylactic use of antidiarrheal treatment was not
required on HER2CLIMB. If diarrhea occurs, administer antidiarrheal
treatment as clinically indicated. Perform diagnostic tests as
clinically indicated to exclude other causes of diarrhea. Based on
the severity of the diarrhea, interrupt dose, then dose reduce or
permanently discontinue TUKYSA.
- Hepatotoxicity – TUKYSA can cause severe hepatotoxicity.
In HER2CLIMB, 8% of patients who received TUKYSA had an ALT
increase >5 × ULN, 6% had an AST increase >5 × ULN, and 1.5%
had a bilirubin increase >3 × ULN (Grade ≥3). Hepatotoxicity led
to dose reduction of TUKYSA in 8% of patients and discontinuation
of TUKYSA in 1.5% of patients. Monitor ALT, AST, and bilirubin
prior to starting TUKYSA, every 3 weeks during treatment, and as
clinically indicated. Based on the severity of hepatotoxicity,
interrupt dose, then dose reduce or permanently discontinue
TUKYSA.
- Embryo-Fetal Toxicity – TUKYSA can cause fetal harm.
Advise pregnant women and females of reproductive potential risk to
a fetus. Advise females of reproductive potential, and male
patients with female partners of reproductive potential, to use
effective contraception during TUKYSA treatment and for at least 1
week after the last dose.
Adverse Reactions
Serious adverse reactions occurred in 26% of patients who
received TUKYSA. Serious adverse reactions in ≥2% of patients who
received TUKYSA were diarrhea (4%), vomiting (2.5%), nausea (2%),
abdominal pain (2%), and seizure (2%). Fatal adverse reactions
occurred in 2% of patients who received TUKYSA including sudden
death, sepsis, dehydration, and cardiogenic shock.
Adverse reactions led to treatment discontinuation in 6% of
patients who received TUKYSA; those occurring in ≥1% of patients
were hepatotoxicity (1.5%) and diarrhea (1%). Adverse reactions led
to dose reduction in 21% of patients who received TUKYSA; those
occurring in ≥2% of patients were hepatotoxicity (8%) and diarrhea
(6%).
The most common adverse reactions in patients who received
TUKYSA (≥20%) were diarrhea, palmar-plantar erythrodysesthesia,
nausea, fatigue, hepatotoxicity, vomiting, stomatitis, decreased
appetite, abdominal pain, headache, anemia, and rash.
Lab Abnormalities
In HER2CLIMB, Grade ≥3 laboratory abnormalities reported in ≥5%
of patients who received TUKYSA were: decreased phosphate,
increased ALT, decreased potassium, and increased AST. The mean
increase in serum creatinine was 32% within the first 21 days of
treatment with TUKYSA. The serum creatinine increases persisted
throughout treatment and were reversible upon treatment completion.
Consider alternative markers of renal function if persistent
elevations in serum creatinine are observed.
Drug Interactions
- Strong CYP3A or Moderate CYP2C8 Inducers: Concomitant
use may decrease TUKYSA activity. Avoid concomitant use of
TUKYSA.
- Strong or Moderate CYP2C8 Inhibitors: Concomitant use of
TUKYSA with a strong CYP2C8 inhibitor may increase the risk of
TUKYSA toxicity; avoid concomitant use. Increase monitoring for
TUKYSA toxicity with moderate CYP2C8 inhibitors.
- CYP3A Substrates: Concomitant use may increase the
toxicity associated with a CYP3A substrate. Avoid concomitant use
of TUKYSA where minimal concentration changes may lead to serious
or life-threatening toxicities. If concomitant use is unavoidable,
decrease the CYP3A substrate dosage.
- P-gp Substrates: Concomitant use may increase the
toxicity associated with a P-gp substrate. Consider reducing the
dosage of P-gp substrates where minimal concentration changes may
lead to serious or life-threatening toxicity.
Use in Specific Populations
- Lactation: Advise women not to breastfeed while taking
TUKYSA and for at least 1 week after the last dose.
- Renal Impairment: Use of TUKYSA in combination with
capecitabine and trastuzumab is not recommended in patients with
severe renal impairment (CLcr < 30 mL/min), because capecitabine
is contraindicated in patients with severe renal impairment.
- Hepatic Impairment: Reduce the dose of TUKYSA for
patients with severe (Child-Pugh C) hepatic impairment.
For more information, please see the full Prescribing
Information for TUKYSA here.
About Seagen
Seagen is a global biotechnology company that discovers,
develops and commercializes transformative cancer medicines to make
a meaningful difference in people’s lives. Seagen is headquartered
in the Seattle, Washington area, and has locations in California,
Canada, Switzerland and the European Union. For more information on
the company’s marketed products and robust pipeline, visit
www.seagen.com and follow @SeagenGlobal on Twitter.
Forward Looking Statements
Certain statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of TUKYSA including its efficacy, safety and therapeutic
uses. Actual results or developments may differ materially from
those projected or implied in these forward-looking statements.
Factors that may cause such a difference include the difficulty and
uncertainty of pharmaceutical product development, the risk of
adverse events or safety signals, the inability to show sufficient
activity in clinical trials and the possibility of adverse
regulatory actions. More information about the risks and
uncertainties faced by Seagen is contained under the caption “Risk
Factors” included in the company’s Quarterly Report on Form 10-Q
for the quarter ended September 30, 2020 filed with the Securities
and Exchange Commission. Seagen disclaims any intention or
obligation to update or revise any forward-looking statements,
whether as a result of new information, future events or otherwise,
except as required by law.
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version on businesswire.com: https://www.businesswire.com/news/home/20201208005451/en/
Peggy Pinkston (425) 527-4160 ppinkston@seagen.com
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