– Simultaneously Published by the Journal of
Clinical Oncology –
Gilead Sciences, Inc. (Nasdaq: GILD) today announced detailed
results from the Phase 3 EVOKE-01 study that will be presented
during an oral session (Abstract #LBA8500) today (2:45-5:45pm CT)
at the 2024 American Society of Clinical Oncology (ASCO) Annual
Meeting. The results were also published simultaneously in the
Journal of Clinical Oncology. The company previously announced that
the study did not meet the primary endpoint of overall survival
(OS) in previously treated metastatic non-small cell lung cancer
(NSCLC).
EVOKE-01, evaluating Trodelvy® (sacituzumab govitecan-hziy; SG)
vs. docetaxel, showed a 16% reduction in the risk of death (median
OS: 11.1 vs. 9.8 months; HR: 0.84; 95% CI: 0.68-1.04; 1-sided
p=0.0534) in patients with metastatic or advanced NSCLC that had
progressed on or after platinum-based chemotherapy and
anti-PD-(L)1-therapy. This numerical improvement in OS was observed
consistently across both squamous and non-squamous histology. In
patients with high unmet medical need whose tumors did not respond
to last anti-PD-(L)1-containing treatment, a meaningful OS
improvement of 3.5 months was seen when treated with Trodelvy vs.
docetaxel (mOS: 11.8 vs. 8.3 months; HR: 0.75; 95% CI: 0.58-0.97).
This subgroup represents approximately 2/3 of the study population.
This pre-specified subgroup analysis was not alpha-controlled for
formal statistical testing.
For the subgroup of patients whose mNSCLC was responsive to last
anti-PD-(L)1-containing treatment, median OS was 9.6 vs. 10.6
months when treated with Trodelvy vs. docetaxel (HR: 1.09; 95% CI:
0.76-1.56). In the overall study population numerically more
patients were alive at 12-months when treated with Trodelvy
compared to docetaxel (46.6% vs. 36.7%).
In the study, Grade ≥3 adverse events (AEs) were lower among
patients receiving Trodelvy (66.6%) vs. docetaxel (75.7%), and AEs
leading to discontinuation were lower with Trodelvy (9.8%) vs.
docetaxel (16.7%). The most common AEs of any grade for Trodelvy
were fatigue (57%), diarrhea (53%), and alopecia (43%) and for
docetaxel were fatigue (56%), neutropenia (43%) and diarrhea (34%).
Patients treated with docetaxel had a greater incidence of
neutropenia of any grade compared with Trodelvy (43% vs. 38%,
respectively), while patients treated with Trodelvy experienced
more diarrhea of any grade vs. docetaxel (53% vs. 34%,
respectively). The safety profile for Trodelvy was consistent with
prior studies, with no new safety signals identified in this
patient population.
“Treating patients with metastatic NSCLC who have progressed on
available treatments continues to be a challenge. After
progression, standard of care for most patients is limited to
single-agent chemotherapy, which offers modest benefit,” said Dr.
Luis Paz-Ares, PhD, Head of the Medical Oncology Service at the
Hospital Universitario 12 de Octubre, Madrid. “These data,
including the meaningful benefit observed in the sub-group of
patients, are encouraging and warrants further investigation as
these patients have a great unmet need.”
“Our data in metastatic NSCLC demonstrating Trodelvy’s activity
continue to advance our understanding of the potential to build on
our impact for patients,” said Merdad Parsey, MD, PhD, Chief
Medical Officer, Gilead Sciences. “We look forward to further
investigating how these data may positively impact patients in the
second-line setting. We would also like to thank the patients,
families, investigators and advocates who contributed to this
important research.”
In addition to the EVOKE-01 presentation at the 2024 ASCO Annual
Meeting, Gilead will present data from its broader lung cancer
clinical development program. Longer-term results from Cohort A of
the Phase 2 EVOKE-02 study of Trodelvy in combination with
KEYTRUDA® (pembrolizumab) in first-line metastatic PD-L1 ≥50% NSCLC
will also be presented in a poster session (Abstract #8592) on June
3, 2024. These data show a median progression-free survival (PFS)
of 13.1 months and support promising activity in this patient
population in both squamous and non-squamous histologies. These
data continue to support our ongoing Phase 3 EVOKE-03 study in
PD-L1-high mNSCLC. In addition, Gilead has a broad clinical
development program in lung cancer with domvanalimab, the first
Fc-silent investigational anti-TIGIT antibody, and the
investigational anti-PD-L1, zimberelimab.
Trodelvy is the first approved Trop-2-directed antibody-drug
conjugate (ADC) that has demonstrated meaningful survival
advantages in two different types of metastatic breast cancers and
shown improved clinical outcomes for certain people with 2L
advanced or metastatic urothelial cancer.
Trodelvy has not been approved by any regulatory agency for the
treatment of metastatic NSCLC. Its safety and efficacy have not
been established for this indication. Trodelvy has a Boxed Warning
for severe or life-threatening neutropenia and severe diarrhea;
please see below for the approved U.S. Indication and additional
Important Safety Information.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme
LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.
About Metastatic Non-Small Cell Lung
Cancer
Worldwide, more than two million people were diagnosed with lung
cancer in 2020. Non-small cell lung cancer (NSCLC) is the most
common type of lung cancer, accounting for up to 85% of diagnoses.
About half of NSCLC cases are diagnosed at the metastatic stage
(57%), when treatment is especially difficult. Even in patients
whose disease is caught early, half will eventually progress to the
metastatic stage within five years. Newly diagnosed patients have
several treatment options including platinum-based therapy,
checkpoint inhibitors and targeted therapies. However, there are
limited treatment options once patients with metastatic NSCLC
progress on or after platinum-based chemotherapy and checkpoint
inhibitors.
About the EVOKE-01 Study
The EVOKE-01 study is a global, multi-center, open-label Phase 3
study randomized 1:1 to evaluate Trodelvy vs. docetaxel in patients
with advanced or metastatic NSCLC that has progressed on or after
platinum-based chemotherapy and checkpoint inhibitor therapy. The
study enrolled 603 participants. The primary endpoint is overall
survival (OS). Key secondary endpoints include progression-free
survival (PFS), objective response rate (ORR), duration of response
(DoR) and disease control rate (DCR) as assessed by investigator
per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and
safety. Additional efficacy measures include time to first
deterioration in shortness of breath domain as measured by NSCLC
Symptom Assessment Questionnaire (NSCLC-SAQ) Score and time to
first deterioration NSCLC-SAQ Total Score. Further study details
are available on clinicaltrials.gov (NCT05089734).
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, bladder and lung 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 tumor microenvironment through a bystander
effect.
Trodelvy is approved in almost 50 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 multiple countries globally to
treat certain patients with pre-treated HR+/HER2- metastatic breast
cancer in Australia, Brazil, Canada, the European Union, Israel,
United Arab Emirates and the United States. In the U.S., Trodelvy
has an accelerated approval for treatment of certain patients with
second-line or later advanced or metastatic urothelial cancer; see
below for full indication statements and please see yesterday’s
announcement of topline results from Gilead’s Phase 3 TROPiCS-04
study in locally advanced or metastatic urothelial cancer.
Trodelvy is being explored for potential investigational use in
other TNBC, HR+/HER2- and metastatic UC populations, as well as a
range of tumor types where Trop-2 is highly expressed, including
metastatic non-small cell lung cancer (NSCLC), head and neck
cancer, gynecological cancer, and gastrointestinal cancers.
U.S. Indications for
Trodelvy
In the United States, Trodelvy is indicated for the treatment of
adult patients with:
- Unresectable locally advanced or metastatic triple-negative
breast cancer (mTNBC) who have received two or more prior systemic
therapies, at least one of them for metastatic disease.
- Unresectable locally advanced or metastatic hormone receptor
(HR)-positive, human epidermal growth factor receptor 2
(HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who
have received endocrine-based therapy and at least two additional
systemic therapies in the metastatic setting.
- Locally advanced or metastatic urothelial cancer (mUC) 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 confirmatory
trials.
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. At the onset of 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
64% of patients treated with Trodelvy. Grade 3-4 neutropenia
occurred in 49% of patients. Febrile neutropenia occurred in 6%.
Neutropenic colitis occurred in 1.4%. 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. Administer G-CSF as clinically
indicated or indicated in Table 1 of USPI.
Diarrhea: Diarrhea occurred in 64% of all patients treated with
Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One
patient had intestinal perforation following diarrhea. Diarrhea
that led to dehydration and subsequent acute kidney injury occurred
in 0.7% of all 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 35% of patients.
Grade 3-4 hypersensitivity occurred in 2% of patients. The
incidence of hypersensitivity reactions leading to permanent
discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic
reactions was 0.2%. Pre-infusion medication is recommended. Have
medications and emergency equipment to treat such reactions
available for immediate use. Observe patients closely for
hypersensitivity and infusion-related reactions during each
infusion and for at least 30 minutes after completion of each
infusion. Permanently discontinue Trodelvy for Grade 4
infusion-related reactions.
Nausea and Vomiting: Nausea occurred in 64% of all patients
treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these
patients. Vomiting occurred in 35% of patients and Grade 3-4
vomiting occurred in 2% 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 58% in patients
homozygous for the UGT1A1*28, 49% in patients heterozygous for the
UGT1A1*28 allele, and 43% in patients homozygous for the wild-type
allele. The incidence of Grade 3-4 anemia was 21% in patients
homozygous for the UGT1A1*28 allele, 10% in patients heterozygous
for the UGT1A1*28 allele, and 9% 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 pooled safety population, the most common (≥ 25%) adverse
reactions including laboratory abnormalities were decreased
leukocyte count (84%), decreased neutrophil count (75%), decreased
hemoglobin (69%), diarrhea (64%), nausea (64%), decreased
lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation
(37%), increased glucose (37%), decreased albumin (35%), vomiting
(35%), decreased appetite (30%), decreased creatinine clearance
(28%), increased alkaline phosphatase (28%), decreased magnesium
(27%), decreased potassium (26%), and decreased sodium (26%).
In the ASCENT study (locally advanced or metastatic
triple-negative breast cancer), the most common adverse reactions
(incidence ≥25%) were fatigue, diarrhea, nausea, alopecia,
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 TROPiCS-02 study (locally advanced or metastatic
HR-positive, HER2-negative breast cancer), the most common adverse
reactions (incidence ≥25%) were diarrhea, fatigue, nausea,
alopecia, and constipation. The most frequent serious adverse
reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia
(4%), neutropenia (3%), abdominal pain, colitis, neutropenic
colitis, pneumonia, and vomiting (each 2%). SAR were reported in
28% of patients, and 6% discontinued therapy due to adverse
reactions. The most common Grade 3-4 lab abnormalities (incidence
≥25%) in the TROPiCS-02 study were reduced neutrophils and
leukocytes.
In the TROPHY study (locally advanced or metastatic urothelial
cancer), the most common adverse reactions (incidence ≥25%) were
diarrhea, fatigue, nausea, any infection, alopecia, decreased
appetite, constipation, vomiting, rash, and abdominal pain. 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 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, COVID-19, 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 the EVOKE-01 study and those
involving Trodelvy and domvanalimab; uncertainties relating to
regulatory applications and related filing and approval timelines,
including pending or potential applications for Trodelvy for the
treatment of metastatic and other TNBC, HR+/HER2- metastatic breast
cancer, metastatic UC, metastatic NSCLC, head and neck cancer,
gynecological cancer and gastrointestinal cancer, and for
domvanalimab; Gilead’s ability to receive regulatory approvals for
programs and/or indications that are currently under evaluation 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
programs for indications that are currently under evaluation,
including Trodelvy for treatment of metastatic NSCLC and
domvanalimab, and as a result, these programs may never be
commercialized for such 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 March 31, 2024, 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 or call Gilead Public
Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20240530725767/en/
Jacquie Ross, Investors investor_relations@gilead.com Ashleigh
Koss, Media public_affairs@gilead.com
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