– Data Across 30 Abstracts Reinforce
Leadership in Metastatic Breast Cancer and Demonstrate Breadth of
Pipeline Across Lung, Hematologic, Genitourinary, Gastrointestinal,
Gynecological and Other Solid Tumors –
– Late-Breaking Presentation to Detail
Overall Survival Results for Yescarta® CAR T-Cell Therapy, Showing
Statistical Improvement Over Standard of Care for Initial Treatment
of Relapsed/Refractory Large B-Cell Lymphoma –
– Updated Interim Results from Phase 2 ARC-7
Study of Fc-Silent Anti-TIGIT Monoclonal Antibody Domvanalimab to
be Featured in Oral Presentation –
Gilead Sciences, Inc. (Nasdaq: GILD) and Kite, a Gilead Company,
will present 30 abstracts during the 2023 American Society of
Clinical Oncology (ASCO) Annual Meeting. These data reinforce the
strength of Gilead and Kite Oncology’s transformative science in
hard-to-treat cancers.
“The breadth of data being presented at ASCO is a testament to
our commitment in helping to bring more life to people with
cancer,” said Bill Grossman, MD, PhD, Senior Vice President,
Therapeutic Area Head, Gilead Oncology. “We are determined to
deliver the best outcomes for patients and are proud to highlight
the pan-tumor efficacy of Trodelvy as well as our growing presence
across lung cancer and many other tumor types.”
New Data Reinforce Pan-Tumor Efficacy of Trodelvy®
Final overall survival (OS) results from the Phase 3 TROPiCS-02
study for Trodelvy® (sacituzumab govitecan-hziy) in HR+/HER2-
metastatic breast cancer (mBC) will be presented in an oral
session. Gilead will also share data evaluating Trodelvy in
metastatic urothelial cancer (UC); in the U.S., Trodelvy currently
has an accelerated approval for the treatment of certain patients
with second-line metastatic UC. Additionally, Gilead will present
the first Phase 2 data evaluating Trodelvy as a potential therapy
in advanced endometrial cancer.
Kite Therapies Continue to Advance the Standard of Care in
Leukemia and Lymphoma
A late-breaking oral presentation from the landmark Phase 3
ZUMA-7 study will highlight OS results for Yescarta® (axicabtagene
ciloleucel) versus standard of care for initial treatment of adult
patients with relapsed/refractory large B-cell lymphoma (LBCL)
within 12 months of completion of first-line therapy. Further
analysis of the pivotal ZUMA-3 study in adult B-cell acute
lymphoblastic leukemia, in addition to real-world evidence in
follicular lymphoma and mantle cell lymphoma, will also be
presented.
“The data that will be presented at ASCO represent another
significant step forward in our goal of bringing the hope of
survival to more patients through our innovative cell therapies,”
said Frank Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical
Development. “We are particularly excited to share our overall
survival data from the pivotal ZUMA-7 study for Yescarta for
initial treatment of relapsed/refractory large B-cell lymphoma, the
first and only treatment in 30 years to demonstrate a statistically
significant improvement in overall survival versus historical
standard of care in this patient population.”
Gilead Highlights Emerging Lung Cancer Pipeline, Progress in
Solid Tumors
Beyond our ongoing late-stage development program evaluating the
investigational use of Trodelvy in non-small cell lung cancer
(NSCLC), Gilead will highlight clinical data and trial updates from
several other lung cancer trials. This includes an oral
presentation with our partner Arcus Biosciences, on the updated
interim analysis of ARC-7, which will detail updated efficacy and
safety results for domvanalimab, an Fc-silent anti-TIGIT monoclonal
antibody, in first-line NSCLC with PD-L1 tumor proportion score
(TPS) ≥50% without epidermal growth factor receptor or anaplastic
lymphoma kinase (EGFR/ALK) mutations. ARC-7 is an approximately
150-patient randomized Phase 2 study evaluating domvanalimab plus
anti-PD-1 antibody zimberelimab (doublet) and domvanalimab plus
zimberelimab and etrumadenant, an A2a/b adenosine receptor
antagonist (triplet), versus zimberelimab alone.
Further highlighting progress being made across Gilead’s
oncology pipeline, trial updates will be shared from ongoing
studies in lung cancer, triple-negative breast cancer, UC and
several other solid tumors.
Summary of Presentations
Accepted abstracts at the 2023 ASCO Annual Meeting include (all
times CDT):
Tumor Types
Abstract Title
Breast Cancer
Abstract #1003 (Oral Session)
Monday, June 5
12:30 PM
Final Overall Survival (OS) Analysis from
the Phase 3 TROPiCS-02 Study of Sacituzumab Govitecan (SG) in
Patients (Pts) with Hormone Receptor–Positive/HER2-Negative
(HR+/HER2–) Metastatic Breast Cancer (mBC)
Abstract #1082
Sunday, June 4
8:00-11:00 AM
Trop-2 mRNA Expression and Association
with Clinical Outcomes with Sacituzumab Govitecan (SG) in Patients
with HR+/HER2– Metastatic Breast Cancer (mBC): Biomarker Results
from the Phase 3 TROPiCS-02 Study
Abstract #TPS619 (TiP)
Sunday, June 4
8:00-11:00 AM
ASCENT-05/Optimice-RD (AFT-65): Phase 3,
Randomized, Open-Label Study of Adjuvant Sacituzumab Govitecan (SG)
+ Pembrolizumab (Pembro) vs. Pembro ± Capecitabine (Cape) in
Patients (Pts) with Triple-Negative Breast Cancer (TNBC) and
Residual Disease after Neoadjuvant Therapy (NAT) and Surgery
Abstract #TPS1130 (TiP)
Sunday, June 4
8:00-11:00 AM
A Phase 2 Randomized Study of Magrolimab
Combination Therapy in Adult Patients with Unresectable Locally
Advanced or Metastatic Triple-Negative Breast Cancer (mTNBC):
ELEVATE TNBC
ePublication
#e18871
Real-World Clinical Outcomes in Patients
(Pts) with HR+/HER2- Metastatic Breast Cancer (mBC) Treated with
Chemotherapy (CT) in the U.S.
ePublication
e18879
Real-World Outcomes in Patients (Pts) with
Metastatic Triple-Negative Breast Cancer (mTNBC) Treated with
Sacituzumab Govitecan (SG) in 2L+ in the U.S.
ePublication
e18798
Canadian (CAN) Real-World Outcomes for
Relapsed/Recurrent (R/R) Metastatic Triple-Negative Breast Cancer
(mTNBC) in the First-Line or Later (1L+) Setting By Early or Late
Recurrence Status
B-cell Lymphomas
Abstract #LBA107 (Oral Session)
Monday, June 5
10:09 AM
Primary Overall Survival Analysis of the
Phase 3 Randomized ZUMA-7 Study of Axicabtagene Ciloleucel versus
Standard-of-Care Therapy in Relapsed/Refractory Large B-Cell
Lymphoma
Abstract #7547
Monday, June 5
8:00-11:00 AM
Circulating Tumor DNA (ctDNA) by ClonoSEQ
to Monitor Residual Disease after Axicabtagene Ciloleucel (Axi-Cel)
in Large B-Cell Lymphoma (LBCL)
Abstract #TPS7578 (TiP)
Monday, June 5
8:00-11:00 AM
ZUMA-23: A Global, Phase 3, Randomized
Controlled Study of Axicabtagene Ciloleucel versus Standard of Care
as First-Line Therapy in Patients with High-Risk Large B-Cell
Lymphoma
Mantle Cell Lymphoma
Abstract #7507 (Oral Session)
Tuesday, June 6
11:57 AM
Real-World Outcomes of Brexucabtagene
Autoleucel (Brexu-cel) for Relapsed or Refractory (R/R) Mantle Cell
Lymphoma (MCL): A CIBMTR Subgroup Analysis by Prior Treatment
Lung Cancer
Abstract #397600 (Oral Session)
Saturday, June 3
12:48 PM
ARC-7: Randomized Phase 2 Study of
Domvanalimab + Zimberelimab +/- Etrumadenant vs Zimberelimab in
First-Line, Metastatic, PD-L1-High Non-Small Cell Lung Cancer
(NSCLC)
Abstract #9034
Sunday, June 4
8:00-11:00 AM
Molecular Characterization of Resistance
to Immune Checkpoint Inhibitor and Chemotherapy Treatment in
Advanced Non-Small Cell Lung Cancer
Abstract #TPS9155 (TiP)
Sunday, June 4
8:00-11:00 AM
VELOCITY-Lung: A Phase (Ph) 2 Study
Evaluating Safety and Efficacy of Domvanalimab (Dom) + Zimberelimab
(Zim) + Sacituzumab Govitecan (SG), or Etrumadenant (Etruma) + Dom
+ Zim, or Etruma + Zim in Patients (Pts) with Treatment-Naïve
Metastatic Non-Small Cell Lung Cancer (mNSCLC)
Abstract #TPS9141 (TiP)
Sunday, June 4
8:00-11:00 AM
STAR-121: A Phase 3, Randomized Study of
Domvanalimab (DOM) and Zimberelimab (ZIM) in Combination with
Chemotherapy vs. Pembrolizumab (Pembro) and Chemotherapy in
Patients with Untreated Metastatic Non-Small Cell Lung Cancer
(mNSCLC) with No Actionable Gene Alterations
Abstract #TPS9148 (TiP)
Sunday, June 4
8:00-11:00 AM
ARC-10: A phase 3 Study to Evaluate
Zimberelimab + Domvanalimab vs. Pembrolizumab in Front-Line,
PD-L1-High, Locally Advanced or Metastatic Non–Small Cell Lung
Cancer
Abstract #TPS8609 (TiP)
Sunday, June 4
8:00-11:00 AM
Phase 3 Trial of Durvalumab Combined with
Domvanalimab Following Concurrent Chemoradiotherapy (cCRT) in
Patients with Unresectable Stage III NSCLC (PACIFIC-8)
Myelodysplastic Syndromes & Acute
Myeloid Leukemia
ePublication
Abstract #e19072
Incidence of Drug-Induced Myelosuppression
and Associated Adverse Events (AEs), Quality of Life (QoL), and
Medical Resource Use (MRU) in Myelodysplastic Syndromes (MDS) and
Acute Myeloid Leukemia (AML)
Acute Lymphoblastic Leukemia
Abstract #7023
Monday, June 5
8:00-11:00 AM
Impact of Age, Prior Therapies, and
Subsequent Transplant on Long-Term Outcomes of Adults with Relapsed
or Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL)
Treated with Brexucabtagene Autoleucel (Brexu-Cel) In ZUMA-3
Endometrial Cancer
Abstract #5610
Monday, June 5
1:15-4:15 PM
TROPiCS-03, A Phase 2 Basket Study of
Sacituzumab Govitecan (SG) in Patients (Pts) with Metastatic Solid
Tumors: Early Analysis in Pts with Advanced/Metastatic Endometrial
Cancer (EC)
Follicular Lymphoma
Abstract #7509
Monday, June 5
8:00-11:00 AM
1:15-2:45 PM (Poster Discussion)
Real-World Early Outcomes of Axicabtagene
Ciloleucel for Relapsed or Refractory (R/R) Follicular Lymphoma
(FL)
Abstract #TPS7579 (TiP)
Monday, June 5
8:00-11:00 AM
ZUMA-22: A Phase 3, Randomized Controlled
Study of Axicabtagene Ciloleucel (Axi-Cel) versus Standard-Of-Care
Therapy in Patients with Relapsed or Refractory (R/R) Follicular
Lymphoma (FL)
Urothelial Cancer
Abstract #4514
Saturday, June 3
8:00-11:00AM
3:00-4:30 PM (Poster Discussion)
Safety Analysis by UGT1A1 Status of
TROPHY-U-01 Cohort 1, a Phase 2 Study of Sacituzumab Govitecan (SG)
in Patients (pts) With Metastatic Urothelial Cancer (mUC) who
Progressed after Platinum (PT)-Based Chemotherapy and a Checkpoint
Inhibitor (CPI)
Abstract #4579
Saturday, June 3
8:00-11:00 AM
Efficacy of Sacituzumab Govitecan (SG) in
Locally Advanced (LA) or Metastatic Urothelial Cancer (mUC) By
Trophoblast Cell Surface Antigen 2 (Trop-2) Expression
Abstract #TPS4611 (TiP)
Saturday, June 3
8:00-11:00 AM
TROPHY-U-01 Cohort 4 (C4): Sacituzumab
Govitecan (SG) in Combination with Cisplatin (Cis) as First-Line
(1L) Therapy, Followed by Maintenance Avelumab Plus (+) SG or
Zimberelimab (Zim) + SG in Patients (Pts) with Treatment (Tx)-Naïve
Metastatic Urothelial Cancer (mUC)
Gastrointestinal Cancers
Abstract #TPS4206 (TiP)
Monday, June 5
8:00-11:00 AM
STAR-221: A Randomized, Open-Label,
Multicenter, Phase 3 Trial of Domvanalimab, Zimberelimab, and
Chemotherapy vs. Nivolumab and Chemotherapy in Previously
Untreated, Locally Advanced, Unresectable or Metastatic Gastric,
Gastroesophageal Junction, and Esophageal Adenocarcinoma
Head And Neck Cancer
Abstract #TPS6102 (TiP)
Monday, June 5
1:15-4:15 PM
A Phase 2 Study of Magrolimab Combination
Therapy in Patients with Recurrent or Metastatic Head and Neck
Squamous Cell Carcinoma (ELEVATE HNSCC)
Advanced Solid Tumors
Abstract #2524
Saturday, June 3
8:00-11:00 AM
3:00-4:30 PM (Poster Discussion)
A Phase 1 Study of AGEN2373, a CD137
Agonist Antibody Designed to Avoid Hepatoxicity, in Patients with
Advanced Solid Tumors
Abstract #TPS4602 (TiP)
Saturday, June 3
8:00-11:00 AM
ARC-20: A Phase 1 Dose-Escalation and
Dose-Expansion Study to Investigate the Safety, Tolerability, and
Pharmacology of HIF-2α Inhibitor AB521 Monotherapy in Patients with
Clear Cell Renal Cell Carcinoma and Other Solid Tumors
Abstract #TPS9142 (TiP)
Sunday, June 4
8:00-11:00 AM
A Phase 2 Multi-Arm Study of Magrolimab in
Combination with Docetaxel in Patients with Locally Advanced or
Metastatic Solid Tumors (ELEVATE Lung and UC)
Domvanalimab, etrumadenant, magrolimab, zimberelimab and
Trodelvy for NSCLC and endometrial cancer are investigational and
are not approved by the U.S. Food and Drug Administration or any
other regulatory authority. Their safety and efficacy have not been
established.
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 40 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. to treat certain patients
with pre-treated HR+/HER2- metastatic breast cancer and has an
accelerated approval for treatment of certain patients with
second-line metastatic urothelial cancer; see below for full
indication statements.
Trodelvy is also being developed 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), 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 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 Yescarta
Please see full Prescribing Information, including BOXED
WARNING and Medication Guide.
YESCARTA is a CD19-directed genetically modified autologous T
cell immunotherapy indicated for the treatment of:
- Adult patients with large B-cell lymphoma that is refractory to
first-line chemoimmunotherapy or that relapses within 12 months of
first-line chemoimmunotherapy.
- Adult patients with relapsed or refractory large B-cell
lymphoma after two or more lines of systemic therapy, including
diffuse large B-cell lymphoma (DLBCL) not otherwise specified,
primary mediastinal large B-cell lymphoma, high grade B-cell
lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: YESCARTA is not
indicated for the treatment of patients with primary central
nervous system lymphoma.
- Adult patients with relapsed or refractory follicular lymphoma
(FL) after two or more lines of systemic therapy. This indication
is approved under accelerated approval based on response rate.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in confirmatory
trial(s).
U.S. IMPORTANT SAFETY INFORMATION
BOXED WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC
TOXICITIES
- Cytokine Release Syndrome (CRS), including fatal or
life-threatening reactions, occurred in patients receiving
YESCARTA. Do not administer YESCARTA to patients with active
infection or inflammatory disorders. Treat severe or
life-threatening CRS with tocilizumab or tocilizumab and
corticosteroids.
- Neurologic toxicities, including fatal or life-threatening
reactions, occurred in patients receiving YESCARTA, including
concurrently with CRS or after CRS resolution. Monitor for
neurologic toxicities after treatment with YESCARTA. Provide
supportive care and/or corticosteroids as needed.
- YESCARTA is available only through a restricted program
under a Risk Evaluation and Mitigation Strategy (REMS) called the
YESCARTA and TECARTUS REMS Program.
CYTOKINE RELEASE SYNDROME (CRS)
CRS, including fatal or life-threatening reactions, occurred.
CRS occurred in 90% (379/422) of patients with non-Hodgkin lymphoma
(NHL), including ≥ Grade 3 in 9%. CRS occurred in 93% (256/276) of
patients with large B-cell lymphoma (LBCL), including ≥ Grade 3 in
9%. Among patients with LBCL who died after receiving YESCARTA, 4
had ongoing CRS events at the time of death. For patients with LBCL
in ZUMA-1, the median time to onset of CRS was 2 days following
infusion (range: 1-12 days) and the median duration was 7 days
(range: 2-58 days). For patients with LBCL in ZUMA-7, the median
time to onset of CRS was 3 days following infusion (range: 1-10
days) and the median duration was 7 days (range: 2-43 days). CRS
occurred in 84% (123/146) of patients with indolent non-Hodgkin
lymphoma (iNHL) in ZUMA-5, including ≥ Grade 3 in 8%. Among
patients with iNHL who died after receiving YESCARTA, 1 patient had
an ongoing CRS event at the time of death. The median time to onset
of CRS was 4 days (range: 1-20 days) and median duration was 6 days
(range: 1-27 days) for patients with iNHL.
Key manifestations of CRS (≥ 10%) in all patients combined
included fever (85%), hypotension (40%), tachycardia (32%), chills
(22%), hypoxia (20%), headache (15%), and fatigue (12%). Serious
events that may be associated with CRS include cardiac arrhythmias
(including atrial fibrillation and ventricular tachycardia), renal
insufficiency, cardiac failure, respiratory failure, cardiac
arrest, capillary leak syndrome, multi-organ failure, and
hemophagocytic lymphohistiocytosis/macrophage activation
syndrome.
The impact of tocilizumab and/or corticosteroids on the
incidence and severity of CRS was assessed in 2 subsequent cohorts
of LBCL patients in ZUMA-1. Among patients who received tocilizumab
and/or corticosteroids for ongoing Grade 1 events, CRS occurred in
93% (38/41), including 2% (1/41) with Grade 3 CRS; no patients
experienced a Grade 4 or 5 event. The median time to onset of CRS
was 2 days (range: 1-8 days) and the median duration of CRS was 7
days (range: 2-16 days). Prophylactic treatment with
corticosteroids was administered to a cohort of 39 patients for 3
days beginning on the day of infusion of YESCARTA. Thirty-one of
the 39 patients (79%) developed CRS and were managed with
tocilizumab and/or therapeutic doses of corticosteroids with no
patients developing ≥ Grade 3 CRS. The median time to onset of CRS
was 5 days (range: 1-15 days) and the median duration of CRS was 4
days (range: 1-10 days). Although there is no known mechanistic
explanation, consider the risk and benefits of prophylactic
corticosteroids in the context of pre-existing comorbidities for
the individual patient and the potential for the risk of Grade 4
and prolonged neurologic toxicities.
Ensure that 2 doses of tocilizumab are available prior to
YESCARTA infusion. Monitor patients for signs and symptoms of CRS
at least daily for 7 days at the certified healthcare facility, and
for 4 weeks thereafter. Counsel patients to seek immediate medical
attention should signs or symptoms of CRS occur at any time. At the
first sign of CRS, institute treatment with supportive care,
tocilizumab, or tocilizumab and corticosteroids as indicated.
NEUROLOGIC TOXICITIES
Neurologic toxicities (including immune effector cell-associated
neurotoxicity syndrome) that were fatal or life-threatening
occurred. Neurologic toxicities occurred in 78% (330/422) of all
patients with NHL receiving YESCARTA, including ≥ Grade 3 in 25%.
Neurologic toxicities occurred in 87% (94/108) of patients with
LBCL in ZUMA-1, including ≥ Grade 3 in 31% and in 74% (124/168) of
patients in ZUMA-7 including ≥ Grade 3 in 25%. The median time to
onset was 4 days (range: 1-43 days) and the median duration was 17
days for patients with LBCL in ZUMA-1. The median time to onset for
neurologic toxicity was 5 days (range:1- 133 days) and median
duration was 15 days in patients with LBCL in ZUMA-7. Neurologic
toxicities occurred in 77% (112/146) of patients with iNHL,
including ≥ Grade 3 in 21%. The median time to onset was 6 days
(range: 1-79 days) and the median duration was 16 days.
Ninety-eight percent of all neurologic toxicities in patients with
LBCL and 99% of all neurologic toxicities in patients with iNHL
occurred within the first 8 weeks of YESCARTA infusion. Neurologic
toxicities occurred within the first 7 days of infusion for 87% of
affected patients with LBCL and 74% of affected patients with
iNHL.
The most common neurologic toxicities (≥ 10%) in all patients
combined included encephalopathy (50%), headache (43%), tremor
(29%), dizziness (21%), aphasia (17%), delirium (15%), and insomnia
(10%). Prolonged encephalopathy lasting up to 173 days was noted.
Serious events, including aphasia, leukoencephalopathy, dysarthria,
lethargy, and seizures occurred. Fatal and serious cases of
cerebral edema and encephalopathy, including late-onset
encephalopathy, have occurred.
The impact of tocilizumab and/or corticosteroids on the
incidence and severity of neurologic toxicities was assessed in 2
subsequent cohorts of LBCL patients in ZUMA-1. Among patients who
received corticosteroids at the onset of Grade 1 toxicities,
neurologic toxicities occurred in 78% (32/41) and 20% (8/41) had
Grade 3 neurologic toxicities; no patients experienced a Grade 4 or
5 event. The median time to onset of neurologic toxicities was 6
days (range: 1-93 days) with a median duration of 8 days (range:
1-144 days). Prophylactic treatment with corticosteroids was
administered to a cohort of 39 patients for 3 days beginning on the
day of infusion of YESCARTA. Of those patients, 85% (33/39)
developed neurologic toxicities, 8% (3/39) developed Grade 3, and
5% (2/39) developed Grade 4 neurologic toxicities. The median time
to onset of neurologic toxicities was 6 days (range: 1-274 days)
with a median duration of 12 days (range: 1-107 days). Prophylactic
corticosteroids for management of CRS and neurologic toxicities may
result in higher grade of neurologic toxicities or prolongation of
neurologic toxicities, delay the onset and decrease the duration of
CRS.
Monitor patients for signs and symptoms of neurologic toxicities
at least daily for 7 days at the certified healthcare facility, and
for 4 weeks thereafter, and treat promptly.
REMS
Because of the risk of CRS and neurologic toxicities, YESCARTA
is available only through a restricted program called the YESCARTA
and TECARTUS REMS Program which requires that: Healthcare
facilities that dispense and administer YESCARTA must be enrolled
and comply with the REMS requirements and must have on-site,
immediate access to a minimum of 2 doses of tocilizumab for each
patient for infusion within 2 hours after YESCARTA infusion, if
needed for treatment of CRS. Certified healthcare facilities must
ensure that healthcare providers who prescribe, dispense, or
administer YESCARTA are trained about the management of CRS and
neurologic toxicities. Further information is available at
www.YescartaTecartusREMS.com or 1-844-454-KITE (5483).
HYPERSENSITIVITY REACTIONS
Allergic reactions, including serious hypersensitivity reactions
or anaphylaxis, may occur with the infusion of YESCARTA.
SERIOUS INFECTIONS
Severe or life-threatening infections occurred. Infections (all
grades) occurred in 45% of patients with NHL. ≥ Grade 3 infections
occurred in 17% of patients, including ≥ Grade 3 infections with an
unspecified pathogen in 12%, bacterial infections in 5%, viral
infections in 3%, and fungal infections in 1%. YESCARTA should not
be administered to patients with clinically significant active
systemic infections. Monitor patients for signs and symptoms of
infection before and after infusion and treat appropriately.
Administer prophylactic antimicrobials according to local
guidelines.
Febrile neutropenia was observed in 36% of all patients with NHL
and may be concurrent with CRS. In the event of febrile
neutropenia, evaluate for infection and manage with broad-spectrum
antibiotics, fluids, and other supportive care as medically
indicated.
In immunosuppressed patients, including those who have received
YESCARTA, life-threatening and fatal opportunistic infections
including disseminated fungal infections (e.g., candida sepsis and
aspergillus infections) and viral reactivation (e.g., human herpes
virus-6 [HHV-6] encephalitis and JC virus progressive multifocal
leukoencephalopathy [PML]) have been reported. The possibility of
HHV-6 encephalitis and PML should be considered in immunosuppressed
patients with neurologic events and appropriate diagnostic
evaluations should be performed.
Hepatitis B virus (HBV) reactivation, in some cases resulting in
fulminant hepatitis, hepatic failure, and death, can occur in
patients treated with drugs directed against B cells, including
YESCARTA. Perform screening for HBV, HCV, and HIV in accordance
with clinical guidelines before collection of cells for
manufacturing.
PROLONGED CYTOPENIAS
Patients may exhibit cytopenias for several weeks following
lymphodepleting chemotherapy and YESCARTA infusion. ≥ Grade 3
cytopenias not resolved by Day 30 following YESCARTA infusion
occurred in 39% of all patients with NHL and included neutropenia
(33%), thrombocytopenia (13%), and anemia (8%). Monitor blood
counts after infusion.
HYPOGAMMAGLOBULINEMIA B-cell aplasia and
hypogammaglobulinemia can occur. Hypogammaglobulinemia was reported
as an adverse reaction in 14% of all patients with NHL. Monitor
immunoglobulin levels after treatment and manage using infection
precautions, antibiotic prophylaxis, and immunoglobulin
replacement. The safety of immunization with live viral vaccines
during or following YESCARTA treatment has not been studied.
Vaccination with live virus vaccines is not recommended for at
least 6 weeks prior to the start of lymphodepleting chemotherapy,
during YESCARTA treatment, and until immune recovery following
treatment.
SECONDARY MALIGNANCIES
Secondary malignancies may develop. Monitor life-long for
secondary malignancies. In the event that one occurs, contact Kite
at 1-844-454-KITE (5483) to obtain instructions on patient samples
to collect for testing.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Due to the potential for neurologic events, including altered
mental status or seizures, patients are at risk for altered or
decreased consciousness or coordination in the 8 weeks following
YESCARTA infusion. Advise patients to refrain from driving and
engaging in hazardous occupations or activities, such as operating
heavy or potentially dangerous machinery, during this initial
period.
ADVERSE REACTIONS
The most common non-laboratory adverse reactions (incidence ≥
20%) in patients with LBCL in ZUMA-7 included fever, CRS, fatigue,
hypotension, encephalopathy, tachycardia, diarrhea, headache,
musculoskeletal pain, nausea, febrile neutropenia, chills, cough,
infection with unspecified pathogen, dizziness, tremor, decreased
appetite, edema, hypoxia, abdominal pain, aphasia, constipation,
and vomiting.
The most common adverse reactions (incidence ≥ 20%) in patients
with LBCL in ZUMA-1 included CRS, fever, hypotension,
encephalopathy, tachycardia, fatigue, headache, decreased appetite,
chills, diarrhea, febrile neutropenia, infections with pathogen
unspecified, nausea, hypoxia, tremor, cough, vomiting, dizziness,
constipation, and cardiac arrhythmias.
The most common non-laboratory adverse reactions (incidence ≥
20%) in patients with iNHL in ZUMA-5 included fever, CRS,
hypotension, encephalopathy, fatigue, headache, infections with
pathogen unspecified, tachycardia, febrile neutropenia,
musculoskeletal pain, nausea, tremor, chills, diarrhea,
constipation, decreased appetite, cough, vomiting, hypoxia,
arrhythmia, and dizziness.
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.
About Kite
Kite, a Gilead Company, is a global biopharmaceutical company
based in Santa Monica, California, focused on cell therapy to treat
and potentially cure cancer. As the global cell therapy leader,
Kite has treated more patients with CAR T-cell therapy than any
other company. Kite has the largest in-house cell therapy
manufacturing network in the world, spanning process development,
vector manufacturing, clinical trial supply and commercial product
manufacturing. For more information on Kite, please visit
www.kitepharma.com. Follow Kite on social media on Twitter
(@KitePharma) and LinkedIn.
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 the ability of Gilead and Kite 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 studies, including those involving Trodelvy,
Yescarta, domvanalimab, etrumadenant, magrolimab and zimberelimab;
the possibility that Gilead and Kite may make a strategic decision
to discontinue development of these programs and, as a result,
these programs may never be successfully commercialized for the
indications currently under evaluation; and any assumptions
underlying any of the foregoing. These and other risks,
uncertainties and factors are described in detail in Gilead’s
Quarterly Report on Form 10-Q for the quarter ended March 31, 2023,
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 Kite,
and Gilead and Kite assume no obligation and disclaim any intent to
update any such forward-looking statements.
Trodelvy, Yescarta, Gilead, the Gilead logo,
Kite and the Kite 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.
For more information on Kite, please visit the
company’s website at www.kitepharma.com. Follow Kite on social
media on Twitter (@KitePharma) and LinkedIn.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20230516005951/en/
Jacquie Ross, Investors investor_relations@gilead.com
Meaghan Smith, Gilead Media public_affairs@gilead.com
Anna Padula, Kite Media apadula@kitepharma.com
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Aug 2024 to Sep 2024
Gilead Sciences (NASDAQ:GILD)
Historical Stock Chart
From Sep 2023 to Sep 2024