– Patients Whose Disease Changed to
Triple-Negative Had Similar Positive Outcomes to Overall Metastatic
TNBC Population in ASCENT Study –
– Trodelvy Is the First Treatment to
Demonstrate Survival Benefit in Metastatic TNBC –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced new data
from the Phase 3 ASCENT study evaluating Trodelvy® (sacituzumab
govitecan-hziy) in patients with relapsed or refractory metastatic
triple-negative breast cancer (TNBC) who received two or more prior
systemic therapies, at least one of them for metastatic disease. In
a retrospective subgroup analysis, Trodelvy improved
progression-free survival (PFS), overall survival (OS) and
objective response rate (ORR) compared with chemotherapy chosen by
the patients’ physicians in patients who were not initially
diagnosed with TNBC. The results were presented at the European
Society of Medical Oncology (ESMO) Congress 2021 from September
16-21, 2021 (Poster #258P).
“In the metastatic stage of breast cancer, it is not uncommon
for people to change from one subtype to another,” said Javier
Cortés, MD, Head of the International Breast Cancer Center (IBCC),
Madrid and Barcelona, Spain. “Roughly one-third of patients with
TNBC in the ASCENT study were not originally diagnosed with TNBC,
and they still experienced a survival benefit with Trodelvy
compared with chemotherapy. For treating physicians, this
reinforces Trodelvy’s efficacy in more complex patients.”
This analysis included 146 chemotherapy-eligible brain
metastasis-negative patients with an original breast cancer
diagnosis that was not TNBC, of which 70 received Trodelvy and 76
received physician’s choice of chemotherapy. Among these patients,
Trodelvy improved median PFS compared with chemotherapy (4.6 months
vs. 2.3 months; HR: 0.48; P=0.0004), median OS (12.4 months vs. 6.7
months; HR: 0.44; P<0.0001) and ORR (31% vs. 4%). Outcomes were
similar to those of the overall ASCENT trial population.
The safety profile of Trodelvy in this subgroup was consistent
with prior reports from the ASCENT study. Key treatment-related
grade ≥3 adverse events for Trodelvy compared to chemotherapy were
neutropenia (59% vs. 40%), leukopenia (12% vs. 9%), anemia (8% vs.
7%) and diarrhea (7% vs. 0%). There were no treatment-related
deaths with Trodelvy. The Trodelvy U.S. Prescribing Information has
a BOXED WARNING for severe or life-threatening neutropenia and
severe diarrhea; see below for Important Safety Information.
“Trodelvy is already transforming outcomes for patients with
second-line or later metastatic TNBC,” said Bill Grossman, MD, PhD,
Senior Vice President, Oncology Clinical Research, Gilead Sciences.
“Gilead is committed to continued research that further defines the
clinical profile of Trodelvy. As such, we are pleased that this
sub-analysis in patients not initially diagnosed with TNBC
demonstrated similarly strong overall survival, progression-free
survival and response rates as were observed in the overall ASCENT
study population.”
About Triple-Negative Breast
Cancer
TNBC is the most aggressive type of breast cancer and accounts
for approximately 15% of all breast cancers. TNBC is diagnosed more
frequently in younger and premenopausal women and is more prevalent
in Black and Hispanic women. TNBC cells do not have estrogen and
progesterone receptors and have limited HER2. Due to the nature of
TNBC, treatment options are extremely limited compared with other
breast cancer types. TNBC has a higher chance of recurrence and
metastases than other breast cancer types. The average time to
metastatic recurrence for TNBC is approximately 2.6 years compared
with 5 years for other breast cancers, and the relative five-year
survival rate is much lower. Among women with metastatic TNBC, the
five-year survival rate is 12%, compared with 28% for those with
other types of metastatic breast cancer.
About the ASCENT Study
The ASCENT study is a global, open-label, randomized Phase 3
study that enrolled more than 500 patients across 230 study
locations. The study evaluated the efficacy and safety of Trodelvy
compared with a single-agent chemotherapy of the physician’s choice
in patients with unresectable, locally advanced or metastatic TNBC
who had received at least two prior systemic treatments. Patients
were randomized to receive either Trodelvy or a chemotherapy chosen
by the patients’ treating physicians. The primary endpoint was PFS
(as determined by blinded independent central review) in patients
without brain metastases. Secondary endpoints included: PFS for
full study population or intention-to-treat (ITT) population, OS in
both the ITT population and in the subgroup without brain
metastasis, independently determined ORR, duration of response,
time to onset of response according to Response Evaluation Criteria
in Solid Tumors (RECIST 1.1), quality of life and safety. More
information about ASCENT is available at
http://clinicaltrials.gov/show/NCT02574455.
About Trodelvy
Trodelvy (sacituzumab govitecan-hziy) is a first-in-class
antibody and topoisomerase inhibitor conjugate directed to the
Trop-2 receptor, a protein overexpressed in multiple types of
epithelial tumors, including metastatic TNBC and metastatic UC,
where high expression is associated with poor survival and relapse.
Beyond the approvals of Trodelvy in the United States, it is also
approved in Australia, Switzerland, and the UK for adults with
metastatic TNBC. Trodelvy is also under regulatory review in the EU
and Canada, as well as in Singapore through our partner Everest
Medicines. Trodelvy is also being investigated as a potential
treatment for hormone receptor-positive/human epidermal growth
factor receptor 2-negative metastatic breast cancer and metastatic
non-small cell lung cancer. Additional evaluation across multiple
solid tumors is also underway.
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.
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,
including those involving Trodelvy; the possibility of unfavorable
results from ongoing or additional trials, including those
involving Trodelvy; Gilead’s ability to receive regulatory
approvals in a timely manner or at all, including additional
regulatory approvals of Trodelvy for the treatment of metastatic
TNBC, metastatic breast cancer, metastatic UC, metastatic non-small
cell lung cancer and other solid tumors, and the risk that any such
approvals may be subject to significant limitations on use; 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, 2021,
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.
Investors are cautioned that any such forward-looking statements
are not guarantees of future performance and involve risks and
uncertainties and are 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.
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