– Late-breaking results from global Phase 3
confirmatory studies of PADCEV (EV-302) in locally advanced or
metastatic bladder cancer and TIVDAK (innovaTV 301) in recurrent or
metastatic cervical cancer to be included in the ESMO Communication
Activities –
Seagen Inc. (Nasdaq: SGEN) today announced the upcoming
presentation of detailed results from two pivotal Phase 3 studies
at the ESMO Congress 2023. Results from the EV-302 study of PADCEV
(enfortumab vedotin-ejfv) plus KEYTRUDA® (pembrolizumab) in locally
advanced or metastatic urothelial cancer (la/mUC) in the first-line
setting will be presented during a Presidential Symposium at the
Congress. Seagen will also present results from the innovaTV 301
study of TIVDAK (tisotumab vedotin-tftv) compared with chemotherapy
in adults with recurrent or metastatic cervical cancer during the
same Presidential Symposium. Both presentations are included in the
ESMO Communication Activities. Seagen is sharing a total of six
abstracts, including five oral presentations at ESMO this year,
taking place October 20–24, 2023 in Madrid, Spain.
“Seagen is excited to share these new overall survival data and
the prospect of PADCEV and TIVDAK to benefit people living with
cancer. We are also proud of the antibody-drug conjugate technology
that Seagen has pioneered for 25 years and its impact on the
treatment of cancer,” said Roger Dansey, M.D., President, Research
and Development and Chief Medical Officer at Seagen. “From the
beginning, we have been driven by science with the goal of
advancing innovation to improve and extend the lives of people with
cancer who have few treatment options. We look forward to
discussing these latest pivotal data with regulatory authorities as
we work to bring transformative care to more patients.”
Committed to Transforming Care in Bladder Cancer with
PADCEV
PADCEV data will detail results of the EV-302 study, which met
its dual primary endpoints of overall survival (OS) and
progression-free survival (PFS), compared to chemotherapy. An
Independent Data Monitoring Committee determined that OS crossed
the pre-specified efficacy boundary at interim analysis. The safety
results of the combination are consistent with those of PADCEV in
combination with pembrolizumab previously reported in
cisplatin-ineligible patients with la/mUC. The EV-302 trial is
intended to serve as the basis for global submissions and as the
confirmatory trial for the U.S. accelerated approval of this
combination.
EV-302 is a global, randomized Phase 3 study that evaluated
PADCEV, developed in partnership with Astellas, in combination with
Merck’s anti-PD-1 therapy KEYTRUDA in the first-line setting for
adult patients with locally advanced or metastatic urothelial
cancer, who were eligible for cisplatin- or carboplatin-containing
chemotherapy regardless of PD-L1 status.
Additional PADCEV data that will be shared at ESMO include
results from EV-103 Cohort L, which show the potential of PADCEV as
a monotherapy in cis-ineligible patients with muscle invasive
bladder cancer (MIBC). Due to high rates of recurrence in
cis-ineligible MIBC patients, there is an urgent need for effective
treatment options.
Aiming to Address Unmet Need in Cervical Cancer with
TIVDAK
Detailed results from the global Phase 3 innovaTV 301 study
evaluating TIVDAK in recurrent or metastatic cervical cancer
patients with disease progression on or after front-line therapy
who received TIVDAK, compared with chemotherapy alone, will also be
highlighted at ESMO. An Independent Data Monitoring Committee
determined that OS crossed the pre-specified efficacy boundary at
interim analysis. The key alpha-controlled secondary endpoints of
investigator-assessed progression-free survival and objective
response rate also demonstrated statistical significance. The
safety profile of TIVDAK in innovaTV 301 was consistent with the
known safety profile of TIVDAK as presented in the U.S. prescribing
information, and no new safety signals were observed.
TIVDAK is being developed in partnership with Genmab. Subject to
discussions with regulatory authorities, the results from innovaTV
301 are intended to serve as the pivotal confirmatory trial for the
U.S. accelerated approval and support global regulatory
applications.
Advancing a Pipeline of Novel Targeted Cancer
Therapies
Early clinical data from a Phase 1 study of SGN-B7H4V, a wholly
owned vedotin ADC directed to B7-H4, will be shared at ESMO. B7-H4
is a member of the B7 family of immune checkpoint ligands and its
expression is elevated on a variety of solid tumors, including
breast, ovarian, and endometrial cancers.
Key data presentations for Seagen at ESMO 2023 include:
Abstract Title
Abstract #
Presentation Time
Lead Author
Enfortumab Vedotin
EV-302/KEYNOTE-A39: Open-Label, Randomized
Phase 3 Study of Enfortumab Vedotin in Combination with
Pembrolizumab (EV+P) Vs Chemotherapy (Chemo) in Previously
Untreated Locally Advanced Metastatic Urothelial Carcinoma
(la/mUC)
LBA6
Presidential Symposium
(Oral Presentation)
Sunday, Oct. 22
4:30 PM CEST
T. Powles
Study EV-103 Cohort L: Perioperative
treatment with enfortumab vedotin (EV) monotheraphy in cisplatin
(cis)-ineligible patients (pts) w/ muscle invasive bladder cancer
(MIBC)
2365MO
Mini Oral Presentation
Sunday, Oct 22
10:45 AM CEST
S. Sridhar
Tisotumab Vedotin
innovaTV 301/ENGOT-cx12/GOG-3057: A
Global, Randomized, Open-Label, Phase 3 Study of Tisotumab Vedotin
vs Investigator’s Choice of Chemotherapy in 2L or 3L Recurrent or
Metastatic Cervical Cancer
LBA9
Presidential Symposium
(Oral Presentation)
Sunday, Oct. 22
5:22 PM CEST
I. Vergote
Tucatinib
Impact of baseline molecular alterations
on the efficacy of tucatinib (TUC) plus trastuzumab (Tras) for
HER2+, RAS WT metastatic CRC (mCRC) in MOUNTAINEER
5510
Proffered Paper
(Oral Presentation)
Saturday, Oct 21
3:45 PM CEST
J. Strickler
Phase 2 dose optimization results from
MOUNTAINEER-02: A study of tucatinib, trastuzumab, ramucirumab, and
paclitaxel for HER2+ gastroesophageal cancer (GEC)
1523P
Poster
Monday, Oct. 23
9 AM – 5 PM CEST
M. Tehfe
Early Pipeline
First-in-human study of SGN-B7H4V, a
B7-H4-directed vedotin ADC, in patients with advanced solid tumors:
Preliminary results of a phase 1 study (SGNB7H4V-001)
660MO
Mini Oral Presentation
Monday, Oct. 23
5:05 PM CEST
C. Perez
PADCEV (enfortumab vedotin-ejfv) U.S. Indication &
Important Safety Information
BOXED WARNING: SERIOUS SKIN REACTIONS
- PADCEV can cause severe and fatal cutaneous adverse reactions
including Stevens-Johnson syndrome (SJS) and Toxic Epidermal
Necrolysis (TEN), which occurred predominantly during the first
cycle of treatment, but may occur later.
- Closely monitor patients for skin reactions.
- Immediately withhold PADCEV and consider referral for
specialized care for suspected SJS or TEN or severe skin
reactions.
- Permanently discontinue PADCEV in patients with confirmed SJS
or TEN; or Grade 4 or recurrent Grade 3 skin reactions.
Indication
PADCEV, as a single agent, is indicated for the treatment of
adult patients with locally advanced or metastatic urothelial
cancer (mUC) who:
- have previously received a programmed death receptor-1 (PD-1)
or programmed death-ligand 1 (PD-L1) inhibitor and
platinum-containing chemotherapy, or
- are ineligible for cisplatin-containing chemotherapy and have
previously received one or more prior lines of therapy.1
PADCEV, in combination with pembrolizumab, is indicated for the
treatment of adult patients with locally advanced or metastatic
urothelial cancer (mUC) who are not eligible for
cisplatin-containing chemotherapy.1
This indication is approved under accelerated approval based on
tumor response rate and durability of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
Important Safety Information
Warnings and Precautions
Skin reactions Severe cutaneous adverse reactions,
including fatal cases of SJS or TEN occurred in patients treated
with PADCEV. SJS and TEN occurred predominantly during the first
cycle of treatment but may occur later. Skin reactions occurred in
56% (all grades) of the 753 patients treated with PADCEV as a
single agent in clinical trials. Twenty-four percent (24%) of
patients had maculo-papular rash and 33% had pruritus. Grade 3-4
skin reactions occurred in 12% of patients, including
maculo-papular rash, erythematous rash, rash or drug eruption,
symmetrical drug-related intertriginous and flexural exanthema
(SDRIFE), bullous dermatitis, exfoliative dermatitis, and
palmar-plantar erythrodysesthesia. The median time to onset of
severe skin reactions was 0.7 months (range: 0.1 to 6 months).
Among patients experiencing a skin reaction leading to dose
interruption who then restarted PADCEV (n=59), 24% of patients
restarting at the same dose and 16% of patients restarting at a
reduced dose experienced recurrent severe skin reactions. Skin
reactions led to discontinuation of PADCEV in 2.6% of patients.
When PADCEV was given in combination with pembrolizumab, the
incidence of skin reactions, including severe events, occurred at a
higher rate. Skin reactions occurred in 72% (all grades) of the 121
patients treated with PADCEV in combination with pembrolizumab in
clinical trials. The majority of the skin reactions that occurred
with combination therapy included maculo-papular rash, macular rash
and papular rash. Grade 3-4 skin reactions occurred in 20% of
patients (Grade 3: 19%, Grade 4: 0.8%), including maculo-papular
rash, bullous dermatitis, dermatitis, exfoliative dermatitis,
pemphigoid, rash, erythematous rash, macular rash, and papular
rash. A fatal reaction of bullous dermatitis occurred in one
patient (0.8%). The median time to onset of severe skin reactions
was 2.6 months (range: 0.3 to 16 months). Skin reactions led to
discontinuation of PADCEV in 6% of patients. Monitor patients
closely throughout treatment for skin reactions. Consider topical
corticosteroids and antihistamines, as clinically indicated. For
persistent or recurrent Grade 2 skin reactions, consider
withholding PADCEV until Grade ≤1. Withhold PADCEV and refer for
specialized care for suspected SJS, TEN or for Grade 3 skin
reactions. Permanently discontinue PADCEV in patients with
confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin
reactions.
Hyperglycemia and diabetic ketoacidosis (DKA).
Hyperglycemia and diabetic ketoacidosis (DKA), including fatal
events, occurred in patients with and without pre-existing diabetes
mellitus, treated with PADCEV. Patients with baseline hemoglobin
A1C ≥8% were excluded from clinical trials. In clinical trials of
PADCEV as a single agent, 14% of the 753 patients treated with
PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4
hyperglycemia. Fatal events of hyperglycemia and diabetic
ketoacidosis occurred in one patient each (0.1%). The incidence of
Grade 3-4 hyperglycemia increased consistently in patients with
higher body mass index and in patients with higher baseline A1C.
Five percent (5%) of patients required initiation of insulin
therapy for treatment of hyperglycemia. The median time to onset of
hyperglycemia was 0.6 months (range: 0.1 to 20 months).
Hyperglycemia led to discontinuation of PADCEV in 0.4% of patients.
Closely monitor blood glucose levels in patients with, or at risk
for, diabetes mellitus or hyperglycemia. If blood glucose is
elevated (>250 mg/dL), withhold PADCEV.
Pneumonitis/Interstitial Lung Disease (ILD) Severe,
life-threatening or fatal pneumonitis/ILD occurred in patients
treated with PADCEV. In clinical trials of PADCEV as a single
agent, 2.9% of the 753 patients treated with PADCEV had
pneumonitis/ILD of any grade and 0.8% had Grade 3-4. The median
time to onset of pneumonitis/ILD was 2.7 months (range: 0.6 to 6
months). The incidence of pneumonitis/ILD, including severe events
occurred at a higher rate when PADCEV was given in combination with
pembrolizumab. When PADCEV was given in combination with
pembrolizumab, 9% of the 121 patients treated with combination
therapy had pneumonitis/ILD of any grade and 3.3% had Grade 3. A
fatal event of pneumonitis occurred in one patient (0.8%). The
median time to onset of pneumonitis/ILD was 6 months (range: 0.6 to
26 months). Monitor patients for signs and symptoms indicative of
pneumonitis/ILD such as hypoxia, cough, dyspnea or interstitial
infiltrates on radiologic exams. Evaluate and exclude infectious,
neoplastic and other causes for such signs and symptoms through
appropriate investigations. Withhold PADCEV for patients who
develop Grade 2 pneumonitis/ILD and consider dose reduction.
Permanently discontinue PADCEV in all patients with Grade 3 or 4
pneumonitis/ILD.
Peripheral neuropathy (PN) Peripheral neuropathy occurred
in 53% of the 753 patients treated with PADCEV as a single agent in
clinical trials including 40% with sensory neuropathy, 7% with
muscular weakness and 7% with motor neuropathy. Thirty percent of
patients experienced Grade 2 reactions and 5% experienced Grade 3-4
reactions. Peripheral neuropathy occurred in patients treated with
PADCEV with or without preexisting peripheral neuropathy. The
median time to onset of Grade ≥2 peripheral neuropathy was 4.9
months (range: 0.1 to 20 months). Neuropathy led to treatment
discontinuation in 7% of patients. Of the patients who experienced
neuropathy who had data regarding resolution (N = 319), 14% had
complete resolution, 46% had partial improvement, and 40% had no
improvement at the time of their last evaluation. Of the 86% of
patients with residual neuropathy at last evaluation, 51% had Grade
2 or greater neuropathy at the time of their last evaluation. The
incidence of peripheral neuropathy occurred at a higher rate when
PADCEV was given in combination with pembrolizumab. When PADCEV was
given in combination with pembrolizumab, 65% of the 121 patients
treated with combination therapy had peripheral neuropathy of any
grade, 45% had Grade 2 neuropathy, and 3.3% had Grade 3 neuropathy.
The median time to onset of Grade ≥2 peripheral neuropathy was 6
months (range: 0.3 to 25 months). Monitor patients for symptoms of
new or worsening peripheral neuropathy and consider dose
interruption or dose reduction of PADCEV when peripheral neuropathy
occurs. Permanently discontinue PADCEV in patients who develop
Grade ≥3 peripheral neuropathy.
Ocular disorders were reported in 40% of the 384 patients
treated with PADCEV as a single agent in clinical trials in which
ophthalmologic exams were scheduled. The majority of these events
involved the cornea and included events associated with dry eye
such as keratitis, blurred vision, increased lacrimation,
conjunctivitis, limbal stem cell deficiency, and keratopathy. Dry
eye symptoms occurred in 34% of patients, and blurred vision
occurred in 13% of patients, during treatment with PADCEV. The
median time to onset to symptomatic ocular disorder was 1.6 months
(range: 0 to 19 months). Monitor patients for ocular disorders.
Consider artificial tears for prophylaxis of dry eyes and
ophthalmologic evaluation if ocular symptoms occur or do not
resolve. Consider treatment with ophthalmic topical steroids, if
indicated after an ophthalmic exam. Consider dose interruption or
dose reduction of PADCEV for symptomatic ocular disorders.
Infusion site extravasation Skin and soft tissue
reactions secondary to extravasation have been observed after
administration of PADCEV. Of the 753 patients treated with PADCEV
as a single agent in clinical trials, 1.5% of patients experienced
skin and soft tissue reactions, including 0.3% who experienced
Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling,
increased temperature, and pain worsened until 2-7 days after
extravasation and resolved within 1-4 weeks of peak. Two patients
(0.3%) developed extravasation reactions with secondary cellulitis,
bullae, or exfoliation. Ensure adequate venous access prior to
starting PADCEV and monitor for possible extravasation during
administration. If extravasation occurs, stop the infusion and
monitor for adverse reactions.
Embryo-fetal toxicity PADCEV can cause fetal harm when
administered to a pregnant woman. Advise patients of the potential
risk to the fetus. Advise female patients of reproductive potential
to use effective contraception during PADCEV treatment and for 2
months after the last dose. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with PADCEV and for 4 months after the last
dose.
Adverse Reactions
Most common adverse reactions, including laboratory
abnormalities (≥20%) (PADCEV monotherapy)
Rash, aspartate aminotransferase increased, glucose increased,
creatinine increased, fatigue, peripheral neuropathy, lymphocytes
decreased, alopecia, decreased appetite, hemoglobin decreased,
diarrhea, sodium decreased, nausea, pruritus, phosphate decreased,
dysgeusia, alanine aminotransferase increased, anemia, albumin
decreased, neutrophils decreased, urate increased, lipase
increased, platelets decreased, weight decreased and dry skin.
EV-301 Study: 296 patients previously treated with a PD-1/L1
inhibitor and platinum-based chemotherapy.
Serious adverse reactions occurred in 47% of patients treated
with PADCEV; the most common (≥2%) were urinary tract infection,
acute kidney injury (7% each) and pneumonia (5%). Fatal adverse
reactions occurred in 3% of patients, including multiorgan
dysfunction (1.0%), hepatic dysfunction, septic shock,
hyperglycemia, pneumonitis and pelvic abscess (0.3% each). Adverse
reactions leading to discontinuation occurred in 17% of patients;
the most common (≥2%) were PN (5%) and rash (4%). Adverse reactions
leading to dose interruption occurred in 61% of patients; the most
common (≥4%) were PN (23%), rash (11%) and fatigue (9%). Adverse
reactions leading to dose reduction occurred in 34% of patients;
the most common (≥2%) were PN (10%), rash (8%), decreased appetite
and fatigue (3% each). Clinically relevant adverse reactions
(<15%) include vomiting (14%), AST increased (12%),
hyperglycemia (10%), ALT increased (9%), pneumonitis (3%) and
infusion site extravasation (0.7%).
EV-201, Cohort 2 Study: 89 patients previously treated with a
PD-1/L1 inhibitor and not eligible for cisplatin-based
chemotherapy.
Serious adverse reactions occurred in 39% of patients treated
with PADCEV; the most common (≥3%) were pneumonia, sepsis and
diarrhea (5% each). Fatal adverse reactions occurred in 8% of
patients, including acute kidney injury (2.2%), metabolic acidosis,
sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1%
each). Adverse reactions leading to discontinuation occurred in 20%
of patients; the most common (≥2%) was PN (7%). Adverse reactions
leading to dose interruption occurred in 60% of patients; the most
common (≥3%) were PN (19%), rash (9%), fatigue (8%), diarrhea (5%),
AST increased and hyperglycemia (3% each). Adverse reactions
leading to dose reduction occurred in 49% of patients; the most
common (≥3%) were PN (19%), rash (11%) and fatigue (7%). Clinically
relevant adverse reactions (<15%) include vomiting (13%), AST
increased (12%), lipase increased (11%), ALT increased (10%),
pneumonitis (4%) and infusion site extravasation (1%).
EV-103 Study: 121 patients with previously untreated locally
advanced or metastatic urothelial cancer who were not eligible for
cisplatin-containing chemotherapy (PADCEV in combination with
pembrolizumab)
The most common adverse reactions, including laboratory
abnormalities (≥20%), of PADCEV in combination with pembrolizumab
were glucose increased, aspartate aminotransferase increased, rash,
hemoglobin decreased, creatinine increased, peripheral neuropathy,
lymphocytes decreased, fatigue, alanine aminotransferase increased,
sodium decreased, lipase increased, albumin decreased, alopecia,
phosphate decreased, decreased weight, diarrhea, pruritus,
decreased appetite, nausea, dysgeusia, potassium decreased,
neutrophils decreased, urinary tract infection, constipation,
potassium increased, calcium increased, peripheral edema, dry eye,
dizziness, arthralgia, and dry skin.
Serious adverse reactions occurred in 50% of patients treated
with PADCEV in combination with pembrolizumab. The most common
serious adverse reactions (≥2%) were acute kidney injury (7%),
urinary tract infection (7%), urosepsis (5%), sepsis (3.3%),
pneumonia (3.3%), hematuria (3.3%), pneumonitis (3.3%), urinary
retention (2.5%), diarrhea (2.5%), myasthenia gravis (2.5%),
myositis (2.5%), anemia (2.5%), and hypotension (2.5%). Fatal
adverse reactions occurred in 5% of patients treated with
PADCEV in combination with pembrolizumab including sepsis (1.6%),
bullous dermatitis (0.8%), myasthenia gravis (0.8%), and
pneumonitis/ILD (0.8%). Adverse reactions leading to
discontinuation of PADCEV occurred in 36% of patients. The most
common adverse reactions (≥2%) leading to discontinuation of
PADCEV were peripheral neuropathy (20%) and rash (6%). Adverse
reactions leading to dose interruption of PADCEV occurred in 69% of
patients. The most common adverse reactions (≥2%) leading to
dose interruption of PADCEV were peripheral neuropathy (18%),
rash (12%), lipase increased (6%), pneumonitis (6%), diarrhea
(4.1%), acute kidney injury (3.3%), alanine aminotransferase
increased (3.3%), fatigue (3.3%), neutropenia (3.3%), urinary tract
infection (3.3%), amylase increased (2.5%), anemia (2.5%), COVID-19
(2.5%), hyperglycemia (2.5%), and hypotension (2.5%). Adverse
reactions leading to dose reduction of PADCEV occurred in 45% of
patients. The most common adverse reactions (≥2%) leading to
dose reduction of PADCEV were peripheral neuropathy (17%), rash
(12%), fatigue (5%), neutropenia (5%), and diarrhea (4.1%).
Drug Interactions
Effects of other drugs on PADCEV (Dual P-gp and Strong
CYP3A4 Inhibitors)
Concomitant use with dual P-gp and strong CYP3A4 inhibitors may
increase unconjugated monomethyl auristatin E exposure, which may
increase the incidence or severity of PADCEV toxicities. Closely
monitor patients for signs of toxicity when PADCEV is given
concomitantly with dual P-gp and strong CYP3A4 inhibitors.
Specific Populations
Lactation Advise lactating women not to breastfeed during
treatment with PADCEV and for at least 3 weeks after the last
dose.
Hepatic impairment Avoid the use of PADCEV in patients
with moderate or severe hepatic impairment.
For more information, please see the U.S. full Prescribing
Information including BOXED WARNING for PADCEV
here.
About TIVDAK (tisotumab vedotin-tftv) U.S.
Indication and Important Safety Information
TIVDAK is indicated in the U.S. for the treatment of adult
patients with recurrent or metastatic cervical cancer with disease
progression on or after chemotherapy.
This indication is approved under accelerated approval based on
tumor response rate and durability of response. Continued approval
for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
Important Safety Information
BOXED WARNING: OCULAR TOXICITY
TIVDAK caused changes in the corneal epithelium and
conjunctiva resulting in changes in vision, including severe vision
loss, and corneal ulceration. Conduct an ophthalmic exam at
baseline, prior to each dose, and as clinically indicated. Adhere
to premedication and required eye care before, during, and after
infusion. Withhold TIVDAK until improvement and resume, reduce the
dose, or permanently discontinue, based on severity.
WARNINGS AND PRECAUTIONS
Ocular adverse reactions occurred in 60% of patients with
cervical cancer treated with TIVDAK across clinical trials. The
most common were conjunctival adverse reactions (40%), dry eye
(29%), corneal adverse reactions (21%), and blepharitis (8%). Grade
3 ocular adverse reactions occurred in 3.8% of patients, including
severe ulcerative keratitis in 3.2% of patients. One patient
experienced ulcerative keratitis with perforation requiring corneal
transplantation. Cases of symblepharon were reported in patients
with other tumor types treated with TIVDAK at the recommended
dose.
In innovaTV 204, 4% of patients experienced visual acuity
changes to 20/50 or worse including 1% of patients who experienced
a visual acuity change to 20/200. Of the patients who experienced
decreased visual acuity to 20/50 or worse, 75% resolved, including
the patient who experienced decreased visual acuity to 20/200.
Refer patients to an eye care provider for an ophthalmic exam,
including visual acuity and slit lamp exam, at baseline, prior to
each dose, and as clinically indicated. Adhere to premedication and
required eye care to reduce the risk of ocular adverse reactions.
Promptly refer patients to an eye care provider for any new or
worsening ocular signs and symptoms. Withhold dose, reduce the
dose, or permanently discontinue TIVDAK based on the severity of
the adverse reaction.
Peripheral Neuropathy (PN) occurred in 42% of cervical
cancer patients treated with TIVDAK across clinical trials; 8% of
patients experienced Grade 3 PN. PN adverse reactions included
peripheral neuropathy (20%), peripheral sensory neuropathy (11%),
peripheral sensorimotor neuropathy (5%), motor neuropathy (3%),
muscular weakness (3%), and demyelinating peripheral polyneuropathy
(1%). One patient with another tumor type treated with TIVDAK at
the recommended dose developed Guillain-Barre syndrome.
Hemorrhage occurred in 62% of cervical cancer patients
treated with TIVDAK across clinical trials. The most common all
grade hemorrhage adverse reactions were epistaxis (44%), hematuria
(10%), and vaginal hemorrhage (10%). Grade 3 hemorrhage occurred in
5% of patients.
Monitor patients for signs and symptoms of hemorrhage. For
patients experiencing pulmonary or central nervous system (CNS)
hemorrhage, permanently discontinue TIVDAK. For Grade ≥2 hemorrhage
in any other location, withhold until bleeding has resolved, blood
hemoglobin is stable, there is no bleeding diathesis that could
increase the risk of continuing therapy, and there is no anatomical
or pathologic condition that can increase the risk of hemorrhage
recurrence. After resolution, either resume treatment or
permanently discontinue TIVDAK.
Pneumonitis that is severe, life-threatening, or fatal
can occur in patients treated with antibody-drug conjugates
containing vedotin, including TIVDAK. Among patients with cervical
cancer treated with TIVDAK across clinical trials, 2 patients
(1.3%) experienced pneumonitis, including 1 patient who had a fatal
outcome.
Monitor patients for pulmonary symptoms of pneumonitis. Symptoms
may include hypoxia, cough, dyspnea or interstitial infiltrates on
radiologic exams. Infectious, neoplastic, and other causes for
symptoms should be excluded through appropriate investigations.
Withhold TIVDAK for patients who develop persistent or recurrent
Grade 2 pneumonitis and consider dose reduction. Permanently
discontinue TIVDAK in all patients with Grade 3 or 4
pneumonitis.
Severe cutaneous adverse reactions, including events of
fatal or life-threatening Stevens-Johnson syndrome (SJS), can occur
in patients treated with TIVDAK.
Monitor patients for signs or symptoms of severe cutaneous
adverse reactions, which include target lesions, worsening skin
reactions, blistering or peeling of the skin, painful sores in
mouth, nose, throat, or genital area, fever or flu-like symptoms,
and swollen lymph nodes. If signs or symptoms of severe cutaneous
adverse reactions occur, withhold TIVDAK until the etiology of the
reaction has been determined. Early consultation with a specialist
is recommended to ensure greater diagnostic accuracy and
appropriate management. Permanently discontinue TIVDAK for
confirmed Grade 3 or 4 severe cutaneous adverse reactions,
including SJS.
Embryo-fetal toxicity: TIVDAK can cause fetal harm when
administered to a pregnant woman. Advise patients of the potential
risk to a fetus. Advise females of reproductive potential to use
effective contraception during treatment with TIVDAK and for 2
months after the last dose. Advise male patients with female
partners of reproductive potential to use effective contraception
during treatment with TIVDAK and for 4 months after the last
dose.
Adverse Reactions
Serious adverse reactions occurred in 43% of patients; the most
common (≥3%) were ileus (6%), hemorrhage (5%), pneumonia (4%), PN,
sepsis, constipation, and pyrexia (each 3%). Fatal adverse
reactions occurred in 4% of patients who received TIVDAK, including
septic shock, pneumonitis, sudden death, and multisystem organ
failure (each 1%).
Adverse reactions leading to permanent discontinuation occurred
in 13% of patients receiving TIVDAK; the most common (≥3%) were PN
(5%) and corneal adverse reactions (4%). Adverse reactions leading
to dose interruption occurred in 47% of patients; the most common
(≥3%) were PN (8%), conjunctival adverse reactions (4%), and
hemorrhage (4%). Adverse reactions leading to dose reduction
occurred in 23% of patients; the most common (≥3%) were
conjunctival adverse reactions (9%) and corneal adverse reactions
(8%).
The most common (≥25%) adverse reactions, including laboratory
abnormalities, were hemoglobin decreased (52%), fatigue (50%),
lymphocytes decreased (42%), nausea (41%), PN (39%), alopecia
(39%), epistaxis (39%), conjunctival adverse reactions (37%),
hemorrhage (32%), leukocytes decreased (30%), creatinine increased
(29%), dry eye (29%), prothrombin international normalized ratio
increased (26%), activated partial thromboplastin time prolonged
(26%), diarrhea (25%), and rash (25%).
Drug Interactions
Strong CYP3A4 inhibitors: Concomitant use with strong
CYP3A4 inhibitors may increase unconjugated monomethyl auristatin E
(MMAE) exposure, which may increase the risk of TIVDAK adverse
reactions. Closely monitor patients for TIVDAK adverse
reactions.
Use in Specific Populations
Moderate or severe hepatic impairment: MMAE exposure and
adverse reactions are increased. Avoid use.
Lactation: Advise lactating women not to breastfeed
during TIVDAK treatment and for at least 3 weeks after the last
dose.
Please see full prescribing information, including BOXED
WARNING for TIVDAK here.
About Seagen
Seagen Inc. is a global biotechnology company that discovers,
develops and commercializes transformative cancer medicines to make
a meaningful difference in people’s lives. Seagen is headquartered
in the Seattle, Washington area, and has locations in California,
Canada, Switzerland and the European Union. For more information on
our marketed products and robust pipeline, visit www.seagen.com and
follow @SeagenGlobal on Twitter.
Forward-Looking Statements
Certain statements made in this press release are forward
looking, such as those, among others, relating to the therapeutic
potential of PADCEV, TIVDAK, TUKYSA® (tucatinib), SGN-B7H4V and the
company’s other products and product candidates, including their
potential efficacy, safety and therapeutic uses, plans to discuss
results from the EV-302 and innovaTV 301 trials with regulatory
authorities; the potential for results from the EV-302 and innovaTV
301 trials to serve as confirmatory trials for the U.S. accelerated
approvals of PADCEV and TIVDAK, respectively, or to support global
regulatory applications; and Seagen’s pipeline. Actual results or
developments may differ materially from those projected or implied
in these forward-looking statements. Factors that may cause such a
difference include, without limitation, the difficulty and
uncertainty of pharmaceutical product development, including the
risks that the company may experience delays in its clinical trials
or otherwise experience failures or setbacks in its clinical
development programs due to lack of efficacy, adverse events or
other factors, and that adverse regulatory actions may occur. More
information about the risks and uncertainties faced by Seagen is
contained under the caption “Risk Factors” included in the
company’s Quarterly Report on Form 10-Q for the quarter ended June
30, 2023, filed with the Securities and Exchange Commission. Seagen
disclaims any intention or obligation to update or revise any
forward-looking statements, whether as a result of new information,
future events or otherwise, except as required by law.
1 PADCEV [package insert]. Northbrook, IL: Astellas Pharma US,
Inc.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231016360057/en/
For Media David Caouette (310) 430-3476 dcaouette@seagen.com
For Investors Douglas Maffei, Ph.D. (425) 527-4881
dmaffei@seagen.com
Grafico Azioni Seagen (NASDAQ:SGEN)
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Grafico Azioni Seagen (NASDAQ:SGEN)
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