-- 3.2 Month Survival Benefit Demonstrated
in Patients who had Already Received Prior Endocrine-based Therapy
and at Least Two Prior Chemotherapies --
-- Trodelvy Now Shows a Survival Benefit in
both Pre-treated HR+/HER2- Metastatic Breast Cancer and Second-Line
Metastatic Triple-Negative Breast Cancer --
Gilead Sciences, Inc. (Nasdaq: GILD) today announced the
positive overall survival (OS) results from the Phase 3 TROPiCS-02
study evaluating Trodelvy® (sacituzumab govitecan-hziy) versus
comparator chemotherapy (physicians’ choice of chemotherapy, TPC)
in patients with HR+/HER2- metastatic breast cancer who received
endocrine-based therapies and at least two chemotherapies. In the
study, Trodelvy demonstrated a statistically significant and
clinically meaningful improvement of 3.2 months in OS compared to
TPC (median OS: 14.4 months vs. 11.2 months; hazard ratio
[HR]=0.79; [95% confidence interval [CI]: 0.65-0.96]; p=0.02). OS
was a key secondary endpoint of the trial.
These findings will be presented on Friday, September 9 at
4:20pm CEST during the European Society for Medical Oncology (ESMO)
Congress 2022 as a late-breaking oral presentation (#LBA76) in the
Brest Auditorium, Paris Expo Porte de Versailles.
Other key secondary endpoints including objective response rate
(ORR) demonstrated statistically significant improvement in
favoring Trodelvy versus TPC. Time to deterioration (TTD) of Global
Health Status/Quality of Life (QoL) and Fatigue scale per
EORTC-QLQ-C30 also favored Trodelvy versus TPC (QoL: 4.3 months vs.
3.0 months, p=0.006; Fatigue: 2.2 months vs. 1.4 months, p=0.002).
No statistically significant difference in TTD on the Pain Scale
was observed.
“It is outstanding to see a clinically meaningful survival
benefit of over three months for patients with pre-treated
HR+/HER2- metastatic breast cancer,” said Hope S. Rugo, MD,
Professor of Medicine and Director, Breast Oncology and Clinical
Trials Education at the University of California San Francisco
Comprehensive Cancer Center, U.S. “Nearly all patients with
HR+/HER2- metastatic breast cancer will develop resistance to
endocrine-based therapies even in combination with targeted agents,
so these data are welcome news for the breast cancer community. The
results of TROPiCS-02 highlight the potential for sacituzumab
govitecan in patients with pre-treated HR+/HER2- metastatic breast
cancer.”
The safety profile for Trodelvy was consistent with prior
studies, with no new safety signals identified in this patient
population.
“With these data from TROPiCS-02, Trodelvy has now demonstrated
a survival benefit in both pre-treated HR+/HER2- metastatic breast
cancer and second-line metastatic TNBC – two difficult-to-treat
forms of breast cancer,” said Bill Grossman, MD, PhD, Senior Vice
President, Therapeutic Area Head, Gilead Oncology. “Our Gilead
Oncology ambition is to transform care for people with cancer, and
the meaningful improvement in survival benefit seen in the
TROPiCS-02 study with Trodelvy is another step forward in pursuing
this ambition for patients.”
The TROPiCS-02 study met its primary endpoint of
progression-free survival earlier this year; detailed results were
presented during the 2022 American Society of Clinical Oncology
(ASCO) Annual Meeting.
Trodelvy has not been approved by any regulatory agency for the
treatment of HR+/HER2- metastatic breast cancer. Its safety and
efficacy have not been established for this indication. Gilead has
submitted a supplemental Biologics License Application (sBLA) to
the U.S. Food and Drug Administration (FDA) based on data from
TROPiCS-02; these data will also be shared with health authorities
outside the U.S.
Sacituzumab govitecan-hziy is currently included in the National
Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines
in Oncology (NCCN Guidelines®)i. This includes a Category 1
recommendation for use in adult patients with second-line
metastatic triple-negative breast cancer (defined as those who
received at least two prior therapies, with at least one line for
metastatic disease). It also has a Category 2A preferred
recommendation for investigational use in HR+/HER2- advanced breast
cancer after prior treatment including endocrine therapy, a CDK4/6
inhibitor and at least two lines of chemotherapy.
Trodelvy has a Boxed Warning for severe or life-threatening
neutropenia and severe diarrhea; please see below for additional
Important Safety Information.
About HR+/HER2- Breast
Cancer
Hormone receptor-positive/human epidermal growth factor receptor
2-negative (HR+/HER2-) breast cancer is the most common type of
breast cancer and accounts for approximately 70% of all new cases,
or nearly 400,000 diagnoses worldwide each year. Almost one in
three cases of early-stage breast cancer eventually become
metastatic, and among patients with HR+/HER2- metastatic disease,
the five-year relative survival rate is 30%. As patients with
HR+/HER2- metastatic breast cancer become resistant to
endocrine-based therapy, their primary treatment option is limited
to single-agent chemotherapy. In this setting, it is common to
receive multiple lines of chemotherapy regimens over the course of
treatment, and the prognosis remains poor.
About the TROPiCS-02
Study
The TROPiCS-02 study is a global, multicenter, open-label, Phase
3 study, randomized 1:1 to evaluate Trodelvy versus physicians’
choice of chemotherapy (eribulin, capecitabine, gemcitabine, or
vinorelbine) in 543 patients with HR+/HER2- metastatic breast
cancer who were previously treated with endocrine therapy, CDK4/6
inhibitors and two to four lines of chemotherapy for metastatic
disease. The primary endpoint is progression-free survival per
Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as
assessed by blinded independent central review (BICR) for
participants treated with Trodelvy compared to those treated with
chemotherapy. Secondary endpoints include overall survival, overall
response rate, clinical benefit rate and duration of response, as
well as assessment of safety and tolerability and quality of life
measures. In the study, HER2 negativity was defined per American
Society of Clinical Oncology (ASCO) and the College of American
Pathologists (CAP) criteria as immunohistochemistry (IHC) score of
0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH)
test. More information about TROPiCS-02 is available at
https://clinicaltrials.gov/ct2/show/NCT03901339.
About Trodelvy
Trodelvy® (sacituzumab govitecan-hziy) is a first-in-class
Trop-2 directed antibody-drug conjugate. Trop-2 is a cell surface
antigen highly expressed in multiple tumor types, including in more
than 90% of breast and bladder cancers. Trodelvy is intentionally
designed with a proprietary hydrolyzable linker attached to SN-38,
a topoisomerase I inhibitor payload. This unique combination
delivers potent activity to both Trop-2 expressing cells and the
microenvironment.
Trodelvy is approved in more than 35 countries, with multiple
additional regulatory reviews underway worldwide, for the treatment
of adult patients with unresectable locally advanced or metastatic
triple-negative breast cancer (TNBC) who have received two or more
prior systemic therapies, at least one of them for metastatic
disease. Trodelvy is also approved in the U.S. under the
accelerated approval pathway for the treatment of adult patients
with locally advanced or metastatic urothelial cancer (UC) who have
previously received a platinum-containing chemotherapy and either
programmed death receptor-1 (PD-1) or programmed death-ligand 1
(PD-L1) inhibitor.
Trodelvy is also being developed for potential investigational
use in other TNBC and metastatic UC populations, as well as a range
of tumor types where Trop-2 is highly expressed, including hormone
receptor-positive/human epidermal growth factor receptor 2-negative
(HR+/HER2-) metastatic breast cancer, metastatic non-small cell
lung cancer (NSCLC), metastatic small cell lung cancer (SCLC), head
and neck cancer, and endometrial cancer.
U.S. Indications for
Trodelvy
In the United States, Trodelvy is indicated for the treatment
of:
- Adult patients with unresectable locally advanced or metastatic
TNBC who have received two or more prior systemic therapies, at
least one of them for metastatic disease.
- Adult patients with locally advanced or metastatic UC who have
previously received a platinum-containing chemotherapy and either
programmed death receptor-1 (PD-1) or programmed death-ligand 1
(PD-L1) inhibitor. This indication is approved under accelerated
approval based on tumor response rate and duration of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in a confirmatory
trial.
U.S. Important Safety Information for
Trodelvy
BOXED WARNING: NEUTROPENIA AND DIARRHEA
- Severe or life-threatening neutropenia may occur. Withhold
Trodelvy for absolute neutrophil count below 1500/mm3 or
neutropenic fever. Monitor blood cell counts periodically during
treatment. Consider G-CSF for secondary prophylaxis. Initiate
anti-infective treatment in patients with febrile neutropenia
without delay.
- Severe diarrhea may occur. Monitor patients with diarrhea
and give fluid and electrolytes as needed. Administer atropine, if
not contraindicated, for early diarrhea of any severity. At the
onset of late diarrhea, evaluate for infectious causes and, if
negative, promptly initiate loperamide. If severe diarrhea occurs,
withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent
doses.
CONTRAINDICATIONS
- Severe hypersensitivity reaction to Trodelvy.
WARNINGS AND PRECAUTIONS
Neutropenia: Severe, life-threatening, or fatal
neutropenia can occur and may require dose modification.
Neutropenia occurred in 61% of patients treated with Trodelvy.
Grade 3-4 neutropenia occurred in 47% of patients. Febrile
neutropenia occurred in 7%. Withhold Trodelvy for absolute
neutrophil count below 1500/mm3 on Day 1 of any cycle or neutrophil
count below 1000/mm3 on Day 8 of any cycle. Withhold Trodelvy for
neutropenic fever.
Diarrhea: Diarrhea occurred in 65% of all patients
treated with Trodelvy. Grade 3-4 diarrhea occurred in 12% of
patients. One patient had intestinal perforation following
diarrhea. Neutropenic colitis occurred in 0.5% of patients.
Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved
to ≤Grade 1. At onset, evaluate for infectious causes and if
negative, promptly initiate loperamide, 4 mg initially followed by
2 mg with every episode of diarrhea for a maximum of 16 mg daily.
Discontinue loperamide 12 hours after diarrhea resolves. Additional
supportive measures (e.g., fluid and electrolyte substitution) may
also be employed as clinically indicated. Patients who exhibit an
excessive cholinergic response to treatment can receive appropriate
premedication (e.g., atropine) for subsequent treatments.
Hypersensitivity and Infusion-Related Reactions: Serious
hypersensitivity reactions including life-threatening anaphylactic
reactions have occurred with Trodelvy. Severe signs and symptoms
included cardiac arrest, hypotension, wheezing, angioedema,
swelling, pneumonitis, and skin reactions. Hypersensitivity
reactions within 24 hours of dosing occurred in 37% of patients.
Grade 3-4 hypersensitivity occurred in 2% of patients. The
incidence of hypersensitivity reactions leading to permanent
discontinuation of Trodelvy was 0.3%. The incidence of anaphylactic
reactions was 0.3%. Pre-infusion medication is recommended. Observe
patients closely for hypersensitivity and infusion-related
reactions during each infusion and for at least 30 minutes after
completion of each infusion. Medication to treat such reactions, as
well as emergency equipment, should be available for immediate use.
Permanently discontinue Trodelvy for Grade 4 infusion-related
reactions.
Nausea and Vomiting: Nausea occurred in 66% of all
patients treated with Trodelvy and Grade 3 nausea occurred in 4% of
these patients. Vomiting occurred in 39% of patients and Grade 3-4
vomiting occurred in 3% of these patients. Premedicate with a two
or three drug combination regimen (e.g., dexamethasone with either
a 5-HT3 receptor antagonist or an NK1 receptor antagonist as well
as other drugs as indicated) for prevention of chemotherapy-induced
nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3
nausea or Grade 3-4 vomiting and resume with additional supportive
measures when resolved to Grade ≤1. Additional antiemetics and
other supportive measures may also be employed as clinically
indicated. All patients should be given take-home medications with
clear instructions for prevention and treatment of nausea and
vomiting.
Increased Risk of Adverse Reactions in Patients with Reduced
UGT1A1 Activity: Patients homozygous for the uridine
diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at
increased risk for neutropenia, febrile neutropenia, and anemia and
may be at increased risk for other adverse reactions with Trodelvy.
The incidence of Grade 3-4 neutropenia was 67% in patients
homozygous for the UGT1A1*28, 46% in patients heterozygous for the
UGT1A1*28 allele and 46% in patients homozygous for the wild-type
allele. The incidence of Grade 3-4 anemia was 25% in patients
homozygous for the UGT1A1*28 allele, 10% in patients heterozygous
for the UGT1A1*28 allele, and 11% in patients homozygous for the
wild-type allele. Closely monitor patients with known reduced
UGT1A1 activity for adverse reactions. Withhold or permanently
discontinue Trodelvy based on clinical assessment of the onset,
duration and severity of the observed adverse reactions in patients
with evidence of acute early-onset or unusually severe adverse
reactions, which may indicate reduced UGT1A1 function.
Embryo-Fetal Toxicity: Based on its mechanism of action,
Trodelvy can cause teratogenicity and/or embryo-fetal lethality
when administered to a pregnant woman. Trodelvy contains a
genotoxic component, SN-38, and targets rapidly dividing cells.
Advise pregnant women and females of reproductive potential of the
potential risk to a fetus. Advise females of reproductive potential
to use effective contraception during treatment with Trodelvy and
for 6 months after the last dose. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with Trodelvy and for 3 months after the last
dose.
ADVERSE REACTIONS
In the ASCENT study (IMMU-132-05), the most common
adverse reactions (incidence ≥25%) were fatigue, neutropenia,
diarrhea, nausea, alopecia, anemia, constipation, vomiting,
abdominal pain, and decreased appetite. The most frequent serious
adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea
(4%), and pneumonia (3%). SAR were reported in 27% of patients, and
5% discontinued therapy due to adverse reactions. The most common
Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study
were reduced neutrophils, leukocytes, and lymphocytes.
In the TROPHY study (IMMU-132-06), the most common
adverse reactions (incidence ≥25%) were diarrhea, fatigue,
neutropenia, nausea, any infection, alopecia, anemia, decreased
appetite, constipation, vomiting, abdominal pain, and rash. The
most frequent serious adverse reactions (SAR) (≥5%) were infection
(18%), neutropenia (12%, including febrile neutropenia in 10%),
acute kidney injury (6%), urinary tract infection (6%), and sepsis
or bacteremia (5%). SAR were reported in 44% of patients, and 10%
discontinued due to adverse reactions. The most common Grade 3-4
lab abnormalities (incidence ≥25%) in the TROPHY study were reduced
neutrophils, leukocytes, and lymphocytes.
DRUG INTERACTIONS
UGT1A1 Inhibitors: Concomitant administration of Trodelvy
with inhibitors of UGT1A1 may increase the incidence of adverse
reactions due to potential increase in systemic exposure to SN-38.
Avoid administering UGT1A1 inhibitors with Trodelvy.
UGT1A1 Inducers: Exposure to SN-38 may be
substantially reduced in patients concomitantly receiving UGT1A1
enzyme inducers. Avoid administering UGT1A1 inducers with
Trodelvy.
Please see full Prescribing Information,
including BOXED WARNING.
About Gilead Sciences
Gilead Sciences, Inc. is a biopharmaceutical company that has
pursued and achieved breakthroughs in medicine for more than three
decades, with the goal of creating a healthier world for all
people. The company is committed to advancing innovative medicines
to prevent and treat life-threatening diseases, including HIV,
viral hepatitis and cancer. Gilead operates in more than 35
countries worldwide, with headquarters in Foster City,
California.
Forward-Looking
Statements
This press release includes forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
that are subject to risks, uncertainties and other factors,
including Gilead’s ability to initiate, progress or complete
clinical trials within currently anticipated timelines or at all,
and the possibility of unfavorable results from ongoing or
additional clinical trials, including those involving Trodelvy;
uncertainties relating to regulatory applications for Trodelvy and
related filing and approval timelines, including with respect to
the pending sBLA for Trodelvy, and pending or potential
applications for the treatment of metastatic TNBC, mUC, HR+/HER2-
breast cancer, NSCLC, SCLC, head and neck cancer, and endometrial
cancer, in the currently anticipated timelines or at all; Gilead’s
ability to receive regulatory approvals for such indications in a
timely manner or at all, and the risk that any such approvals may
be subject to significant limitations on use; the possibility that
Gilead may make a strategic decision to discontinue development of
Trodelvy for such indications and as a result, Trodelvy may never
be commercialized for these indications; and any assumptions
underlying any of the foregoing. These and other risks,
uncertainties and other factors are described in detail in Gilead’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2022,
as filed with the U.S. Securities and Exchange Commission. These
risks, uncertainties and other factors could cause actual results
to differ materially from those referred to in the forward-looking
statements. All statements other than statements of historical fact
are statements that could be deemed forward-looking statements. The
reader is cautioned that any such forward-looking statements are
not guarantees of future performance and involve risks and
uncertainties, and is cautioned not to place undue reliance on
these forward-looking statements. All forward-looking statements
are based on information currently available to Gilead, and Gilead
assumes no obligation and disclaims any intent to update any such
forward-looking statements.
U.S. Prescribing Information for Trodelvy
including BOXED WARNING, is available at www.gilead.com.
Trodelvy, Gilead and the Gilead logo are
trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit
the company’s website at www.gilead.com, follow Gilead on Twitter
(@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5
or 1-650-574-3000.
i Referenced with permission from the NCCN Clinical Practice
Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer Version
4.2022. © National Comprehensive Cancer Network, Inc. 2022. All
rights reserved. Accessed August 2022. To view the most recent and
complete version of the guideline, go online to NCCN.org. NCCN
makes no warranties of any kind whatsoever regarding their content,
use or application and disclaims any responsibility for their
application or use in any way.
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version on businesswire.com: https://www.businesswire.com/news/home/20220906006036/en/
Jacquie Ross, Investors investor_relations@gilead.com
Nathan Kaiser, Media Nathan.kaiser@gilead.com
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