Company Announcement
- Phase 3 innovaTV 301 confirmatory trial met its primary
endpoint of improved overall survival (OS) at predetermined,
independent interim analysis
- Trial results to be submitted for presentation at a future
medical meeting
- Genmab and Seagen to engage in discussions with regulatory
authorities
Genmab A/S (Nasdaq: GMAB) and Seagen Inc.
(Nasdaq: SGEN) announced today that the Phase 3 innovaTV 301
global trial in recurrent or metastatic cervical cancer patients
with disease progression on or after front-line therapy who
received TIVDAK® (tisotumab vedotin-tftv), compared with
chemotherapy alone, met its primary endpoint of overall survival
(OS). An Independent Data Monitoring Committee determined that OS
crossed the pre-specified efficacy boundary at interim analysis.
The key secondary endpoints of investigator-assessed
progression-free survival and objective response rate also
demonstrated statistical significance. The safety profile of TIVDAK
in innovaTV 301 is consistent with the known safety profile of
TIVDAK as presented in the U.S. prescribing information, and no new
safety signals were observed.
The results of innovaTV 301/ENGOT cx-12/GOG 3057, a global,
randomized, open-label Phase 3 trial, add to the previous results
of innovaTV 204, which served as the basis for the accelerated
approval of TIVDAK in the United States. 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.
The innovaTV 301 China extension study has been initiated and
continues to enroll patients, in collaboration with Zai Lab
Limited.
“TIVDAK is the only U.S. Food and Drug Administration-approved
therapy in second-line recurrent or metastatic cervical cancer
regardless of biomarker status, tumor histology and prior therapy,”
said Roger Dansey, M.D., President of Research and Development and
Chief Medical Officer at Seagen. “Demonstrating a survival benefit
with the results of innovaTV 301 is a critical milestone in our
efforts to ensure more adults living with advanced cervical cancer
have an approved treatment option.”
“With limited options for advanced cervical cancer patients who
have progressed after front-line therapy, there is a need for
therapeutic options with new mechanisms of action, particularly
those with a demonstrated survival benefit,” said Jan van de
Winkel, Ph.D., Chief Executive Officer, Genmab. “These results
provide hope for patients with recurrent or metastatic cervical
cancer.”
Results of the Phase 3 innovaTV 301 clinical trial will be
submitted for presentation at an upcoming medical congress and
discussed with regulatory authorities.
About Cervical Cancer Cervical cancer remains a disease
with high unmet need despite advances in effective vaccination and
screening practices to prevent and diagnose pre-/early-stage
cancers for curative treatment. Recurrent and/or metastatic
cervical cancer is a particularly devastating and mostly incurable
disease; up to 16% of adults are diagnosed with metastatic disease
at diagnosisi,ii and, for adults diagnosed at earlier stages who
receive treatment, up to 61% will experience disease recurrence and
progress to metastatic cervical cancer.iii It is estimated that in
2023, more than 13,960 new cases of invasive cervical cancer will
be diagnosed in the U.S. and 4,310 adults will die from the
disease.iv
About the innovaTV 301 Trial The innovaTV 301 trial
(NCT04697628) is a global, randomized, open-label Phase 3 trial
evaluating TIVDAK® (tisotumab vedotin-tftv) versus
investigator’s choice of chemotherapy alone (topotecan,
vinorelbine, gemcitabine, irinotecan or pemetrexed) in 502 patients
with recurrent or metastatic cervical cancer who received no more
than two prior systemic regimens in the recurrent or metastatic
setting.
Patients with recurrent or metastatic cervical cancer with
squamous cell, adenocarcinoma or adenosquamous histology, and
disease progression during or after treatment with a standard of
care systemic chemotherapy doublet or platinum-based therapy (if
eligible) are included. The main efficacy outcome measure is
overall survival. The main secondary outcomes are progression-free
survival, objective response rate, time to response and duration of
response, as assessed by the investigator, as well as safety and
quality of life outcomes.
The study was conducted by Seagen in collaboration with Genmab,
European Network of Gynaecological Oncological Trial Groups (ENGOT,
study number ENGOT cx-12) and the Gynecologic Oncology Group (GOG)
Foundation (study number GOG 3057). For more information about the
Phase 3 innovaTV 301 clinical trial and other clinical trials with
tisotumab vedotin, please visit www.clinicaltrials.gov.
About TIVDAK® (tisotumab vedotin) TIVDAK® (tisotumab
vedotin) is an antibody-drug conjugate (ADC) composed of Genmab’s
human monoclonal antibody directed to tissue factor (TF) and
Seagen’s ADC technology that utilizes a protease-cleavable linker
that covalently attaches the microtubule-disrupting agent
monomethyl auristatin E (MMAE) to the antibody. Determination of TF
expression is not required. Nonclinical data suggest that the
anticancer activity of TIVDAK is due to the binding of the ADC to
TF-expressing cancer cells, followed by internalization of the
ADC-TF complex, and release of MMAE via proteolytic cleavage. MMAE
disrupts the microtubule network of actively dividing cells,
leading to cell cycle arrest and apoptotic cell death. In vitro,
TIVDAK also mediates antibody-dependent cellular phagocytosis and
antibody-dependent cellular cytotoxicity.
In September 2021, the U.S. Food and Drug Administration granted
accelerated approval for TIVDAK in adult patients with recurrent or
metastatic cervical cancer with disease progression on or after
chemotherapy. TIVDAK is the first and only approved ADC for the
treatment of these patients with recurrent or metastatic cervical
cancer with disease progression on or after chemotherapy. The Phase
3 innovaTV 301 clinical trial, an open-label, randomized, global
trial, is intended as the confirmatory trial for use in verifying
and describing the clinical benefit and for global regulatory
applications.
Indication 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 Genmab Genmab is an international biotechnology
company with a core purpose guiding its unstoppable team to strive
towards improving the lives of patients through innovative and
differentiated antibody therapeutics. For more than 20 years, its
passionate, innovative and collaborative team has invented
next-generation antibody technology platforms and leveraged
translational research and data sciences, which has resulted in a
proprietary pipeline including bispecific T-cell engagers,
next-generation immune checkpoint modulators, effector function
enhanced antibodies and antibody-drug conjugates. To help develop
and deliver novel antibody therapies to patients, Genmab has formed
20+ strategic partnerships with biotechnology and pharmaceutical
companies. By 2030, Genmab’s vision is to transform the lives of
people with cancer and other serious diseases with
Knock-Your-Socks-Off (KYSO™) antibody medicines.
Established in 1999, Genmab is headquartered in Copenhagen,
Denmark with locations in Utrecht, the Netherlands, Princeton, New
Jersey, U.S. and Tokyo, Japan. For more information, please visit
Genmab.com and follow us on Twitter.com/Genmab.
About Seagen Founded 25 years ago, Seagen Inc. is a
global biotechnology company that discovers, develops, manufactures
and commercializes targeted cancer therapeutics, with antibody-drug
conjugates (ADCs) at our core. Our colleagues work together with
urgency to improve and extend the lives of people living with
cancer. An ADC technology trailblazer, approximately one-third of
FDA-approved and marketed ADCs use Seagen technology. Seagen is
headquartered in Bothell, Washington and has locations in
California, Canada, Switzerland and across Europe. For additional
information, visit www.seagen.com and follow us on Twitter and
LinkedIn.
About the Seagen and Genmab Collaboration Tisotumab
vedotin is being co-developed by Genmab and Seagen, under an
agreement in which the companies share costs and profits for the
product on a 50:50 basis.
Genmab Forward Looking Statements This Company
Announcement contains forward looking statements. The words
“believe,” “expect,” “anticipate,” “intend” and “plan” and similar
expressions identify forward looking statements. Actual results or
performance may differ materially from any future results or
performance expressed or implied by such statements. The important
factors that could cause our actual results or performance to
differ materially include, among others, risks associated with
pre-clinical and clinical development of products, uncertainties
related to the outcome and conduct of clinical trials including
unforeseen safety issues, uncertainties related to product
manufacturing, the lack of market acceptance of our products, our
inability to manage growth, the competitive environment in relation
to our business area and markets, our inability to attract and
retain suitably qualified personnel, the unenforceability or lack
of protection of our patents and proprietary rights, our
relationships with affiliated entities, changes and developments in
technology which may render our products or technologies obsolete,
and other factors. For a further discussion of these risks, please
refer to the risk management sections in Genmab’s most recent
financial reports, which are available on www.genmab.com and the
risk factors included in Genmab’s most recent Annual Report on Form
20-F and other filings with the U.S. Securities and Exchange
Commission (SEC), which are available at www.sec.gov. Genmab does
not undertake any obligation to update or revise forward looking
statements in this Company Announcement nor to confirm such
statements to reflect subsequent events or circumstances after the
date made or in relation to actual results, unless required by
law.
Genmab A/S and/or its subsidiaries own the following trademarks:
Genmab®; the Y-shaped Genmab logo®; Genmab in combination with the
Y-shaped Genmab logo®; HuMax®; DuoBody®; HexaBody®; DuoHexaBody®,
HexElect® and KYSO™. Tivdak® is a trademark of Seagen Inc.
Seagen Forward Looking Statements Certain of the
statements made in this press release are forward looking, such as
those, among others, relating to the potential for results from the
innovaTV 301 clinical trial to serve as the confirmatory trial for
the U.S. accelerated approval and support global regulatory
applications; plans to share the results at an upcoming medical
congress and discuss them with regulatory authorities; the conduct
of the ongoing innovaTV 301 trial; and the therapeutic potential of
TIVDAK, including its efficacy, safety and therapeutic uses. 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 the possibility that results from
the innovaTV 301 trial may not be sufficient to support the
conversion of the U.S. accelerated approval of TIVDAK to full
approval or any global regulatory approvals; that adverse events or
safety signals may occur; that adverse regulatory actions may
occur; the possibility of delays, setbacks or failures in clinical
development activities, the submission of regulatory applications
and the regulatory review process for a variety of reasons,
including the inherent difficulty and uncertainty of pharmaceutical
product development; the inability to provide information and
institute safety mitigation measures as may be required by the FDA
or other regulatory authorities from time to time; and failure to
properly conduct or manage clinical trials. 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.
_______________________________ i National Cancer Institute.
SEER Cancer Stat Facts: Cervical Cancer. 2020.
https://seer.cancer.gov/statfacts/html/cervix.html ii McLachlan J,
Boussios S, Okines A, et al. The impact of systemic therapy beyond
first-line treatment for advanced cervical cancer. Clin Oncol (R
Coll Radiol). 2017;29(3):153-60. iii Pfaendler KS, Tewari KS.
Changing paradigms in the systemic treatment of advanced cervical
cancer. Am J Obstet Gynecol. 2016;214(1):22-30. iv Key Statistics
for Cervical Cancer. American Cancer Society. Atlanta, GA. 2023.
https://www.cancer.org/cancer/types/cervical-cancer/about/key-statistics.html
View source
version on businesswire.com: https://www.businesswire.com/news/home/20230904469378/en/
INVESTORS & MEDIA Genmab A/S: For Media:
Marisol Peron, Senior Vice President, Global Communications &
Corporate Affairs (609) 524 0065; mmp@genmab.com
For Investor Relations: Andrew Carlsen, Vice President, Head of
Investor Relations +45 3377 9558; acn@genmab.com
Seagen: For Media: David Caouette Vice President,
Corporate Communications (310) 430-3476 dcaouette@seagen.com
For Investor Relations: Douglas Maffei, Ph.D. Vice President,
Head of Investor Relations & ESG (425) 527-4160
dmaffei@seagen.com
Grafico Azioni Seagen (NASDAQ:SGEN)
Storico
Da Ott 2024 a Dic 2024
Grafico Azioni Seagen (NASDAQ:SGEN)
Storico
Da Dic 2023 a Dic 2024
