- Results from innovaTV207 evaluating tisotumab vedotin,
showing 32.5% confirmed objective response rate in patients with
recurrent or metastatic HNSCC, presented in a rapid oral session at
2024 ASCO® Annual Meeting
- HNSCC is the sixth most common cancer worldwide, with
incidence rates expected to increase 30% by 2030i
Genmab A/S (Nasdaq: GMAB) announced today that
data from the Phase 2 innovaTV 207 trial (NCT03485209) Part C
(n=40), investigating tisotumab vedotin, an antibody-drug conjugate
directed to tissue factor, demonstrated encouraging antitumor
activity as a monotherapy in patients with head and neck squamous
cell carcinoma (HNSCC) who experienced disease progression on or
after first-line therapy. The study showed 32.5% of patients
achieved a confirmed objective response rate (cORR), one patient
experienced a complete response (CR) and 12 achieved a partial
response (PR). These results were presented in a rapid oral session
today at the 2024 ASCO Annual Meeting, being held in Chicago,
Illinois, May 31 – June 4, 2024.
In the HNSCC cohort of innovaTV 207 Part C (n=40), median
duration of response (DOR) was 5.6 months and median
time-to-response (TTR) was 1.4 months. All patients were required
to have received a platinum-based regimen in the recurrent or
metastatic setting or have persistent disease following
platinum-based chemoradiation and a checkpoint inhibitor (CPI), if
eligible. The study also showed that among patients with no more
than one or two lines of therapy in the recurrent or metastatic
setting (n=25), 40% had achieved a cORR at the time of data
cut-off.
“Most patients with recurrent or metastatic head and neck
squamous cell carcinoma experience disease progression despite the
use of platinum-based therapy and immunotherapy, and treatment
options are limited,” said Dr. Judith Klimovsky, Executive Vice
President and Chief Development Officer of Genmab, “These updated
results underscore the importance of our ongoing work with our
partner to advance the clinical development program for tisotumab
vedotin and investigate potential treatment options for pretreated
patients living with unmet needs.”
The safety findings were consistent with previous tisotumab
vedotin trials, and no new safety signals were observed. Grade ≥3
treatment-emergent adverse events (TEAEs) occurred in 67.5% of
patients, and the most common were peripheral neuropathy events
(40%). Adverse events of special interest (of any grade) were
prespecified for ocular, peripheral neuropathy, and bleeding
events, and occurred in 52.5%, 47.5%, and 40% patients,
respectively.
As of December 2023, 40 patients with recurrent or metastatic
HNSCC were treated with tisotumab vedotin monotherapy (1.7 mg/kg
intravenously, once every two weeks). In this cohort, 32 (80%)
received prior platinum-based therapy, 19 (47.5%) received at least
two prior lines of systemic therapy (median: 2; range: 1-3), 40
(100%) received prior CPI, 23 (57.5%) received prior taxane, and 27
(67.5%) received prior cetuximab. The primary sites at diagnosis
were oropharynx (n=16), larynx (n=13), and oral cavity (n=9).
About the innovaTV 207 Trial
The innovaTV 207 trial (NCT03485209) is an open-label, global,
Phase 2, multicohort, multicenter study evaluating tisotumab
vedotin monotherapy or in combination for advanced solid tumors. In
Part C, patients with recurrent or metastatic HNSCC received
tisotumab vedotin monotherapy (1.7 mg/kg IV once every two weeks).
All patients were required to have received a platinum-based
regimen, either in the recurrent/metastatic setting, or to have
persistent disease following platinum-based chemoradiation and a
checkpoint inhibitor, if eligible. The primary endpoint of the
trial is confirmed objective response rate (cORR) per RECIST 1.1
per investigator, defined as the proportion of patients who achieve
a confirmed complete or partial response. Selected secondary
endpoints include duration of response (DOR), time-to-response
(TTR), and safety. For more information about the phase 2 innovaTV
207 clinical trial of tisotumab vedotin, please visit
www.clinicaltrials.gov.
About Tisotumab Vedotin
Tisotumab vedotin is an antibody-drug conjugate (ADC) composed
of Genmab’s human monoclonal antibody directed to tissue factor
(TF) and Pfizer’s ADC technology that utilizes a protease-cleavable
linker that covalently attaches the microtubule-disrupting agent
monomethyl auristatin E (MMAE) to the antibody. Nonclinical data
suggest that the anticancer activity of tisotumab vedotin-tftv 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, tisotumab vedotin-tftv also
mediates antibody-dependent cellular phagocytosis and
antibody-dependent cellular cytotoxicity.
Tisotumab vedotin (TIVDAK®) has received full approval by the
U.S. FDA for the treatment of adult patients with recurrent or
metastatic cervical cancer (r/mCC) with disease progression on or
after chemotherapy. Tisotumab vedotin in HNSCC is not approved in
any country, including the U.S. and the EU. The safety and efficacy
of tisotumab vedotin has not been established for these
investigational uses.
See TIVDAK U.S. Important Safety Information, including Boxed
Warning, below.
Indication
TIVDAK is indicated for the treatment of adult patients with
recurrent or metastatic cervical cancer (r/mCC) with disease
progression on or after chemotherapy.
Important Safety Information
BOXED WARNING: OCULAR TOXICITY
TIVDAK can cause severe ocular toxicities resulting in changes
in vision, including severe vision loss, and corneal ulceration.
Conduct an ophthalmic exam, including an assessment of ocular
symptoms, visual acuity, and slit lamp exam of the anterior segment
of the eye prior to initiation of TIVDAK, prior to every cycle for
the first nine cycles, and as clinically indicated. Adhere to the
required premedication and 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: TIVDAK can cause severe ocular adverse
reactions, including conjunctivitis, keratopathy (keratitis,
punctate keratitis, and ulcerative keratitis), and dry eye
(increased lacrimation, eye pain, eye discharge, pruritus,
irritation, and foreign body sensation), that may lead to changes
in vision and/or corneal ulceration.
Ocular adverse reactions occurred in 55% of patients with
cervical cancer treated with TIVDAK across clinical trials. The
most common were conjunctivitis (32%), dry eye (24%), keratopathy
(17%), and blepharitis (5%). Grade 3 ocular adverse reactions
occurred in 3.3% of patients, including severe ulcerative keratitis
in 1.2% of patients. Nine patients (2.1%) experienced ulcerative
keratitis (including one with perforation requiring corneal
transplantation), six (1.4%) conjunctival ulcer, four (0.9%)
corneal erosion, two (0.5%) conjunctival erosion, and two (0.5%)
symblepharon.
In innovaTV 301, 8 patients (3.2%) experienced delayed ocular
adverse reactions occurring more than 30 days after discontinuation
of TIVDAK. These adverse reactions included 3 patients with
ulcerative keratitis, and one patient (each) with keratitis,
punctate keratitis and corneal erosion, blepharitis and
conjunctival hyperemia, conjunctival scar, and conjunctivitis and
xerophthalmia.
Refer patients to an eye care provider to conduct an ophthalmic
exam prior to initiation of TIVDAK, prior to every cycle for the
first nine cycles, and as clinically indicated. The exam should
include visual acuity, slit lamp exam of the anterior segment of
the eye, and an assessment of normal eye movement and ocular signs
or symptoms which include dry or irritated eyes, eye secretions, or
blurry vision.
Adhere to the required premedication and eye care before,
during, and after infusion to reduce the risk of ocular adverse
reactions. Monitor for ocular toxicity and promptly refer patients
to an eye care provider for any new or worsening ocular signs and
symptoms. Withhold, reduce, or permanently discontinue TIVDAK based
on the severity or persistence of the ocular adverse reaction.
Peripheral Neuropathy (PN) occurred in 39% of cervical cancer
patients treated with TIVDAK across clinical trials; 6% of patients
experienced Grade 3 PN. PN adverse reactions included peripheral
sensory neuropathy (23%), PN (5%), paresthesia (3.8%), peripheral
sensorimotor neuropathy (3.3%), muscular weakness (2.8%), and
peripheral motor neuropathy (2.4%). One patient with another tumor
type treated with TIVDAK at the recommended dose developed
Guillain-Barre syndrome.
Monitor patients for signs and symptoms of neuropathy such as
paresthesia, tingling or a burning sensation, neuropathic pain,
muscle weakness, or dysesthesia. For new or worsening PN, withhold,
then dose reduce, or permanently discontinue TIVDAK based on the
severity of PN.
Hemorrhage occurred in 51% of cervical cancer patients treated
with TIVDAK across clinical trials. The most common all grade
hemorrhage adverse reaction was epistaxis (33%). Grade 3 hemorrhage
occurred in 4% of patients.
Monitor patients for signs and symptoms of hemorrhage. For
patients experiencing pulmonary or central nervous system
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 cervical cancer patients treated
with TIVDAK across clinical trials, 4 patients (0.9%) 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 such
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 (SCAR), including events of
fatal or life-threatening Stevens-Johnson syndrome (SJS), can occur
in patients treated with TIVDAK. SCAR occurred in 1.6% of cervical
cancer patients treated with TIVDAK across clinical trials. Grade
≥3 SCAR occurred in 0.5% of patients, including 1 patient who had a
fatal outcome.
Monitor patients for signs or symptoms of SCAR, 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 SCAR 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 SCAR, 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
Across clinical trials of TIVDAK in 425 patients with r/mCC, the
most common (≥25%) adverse reactions, including laboratory
abnormalities, were hemoglobin decreased (45%), PN (39%),
conjunctival adverse reactions (38%), nausea (37%), fatigue (36%),
aspartate aminotransferase increased (33%), epistaxis (33%),
alopecia (31%), alanine aminotransferase increased (30%), and
hemorrhage (28%).
innovaTV 301 Study: 250 patients with r/mCC with disease
progression on or after systemic therapy
Serious adverse reactions occurred in 33% of patients
receiving TIVDAK; the most common (≥2%) were urinary tract
infection (4.8%), small intestinal obstruction (2.4%), sepsis,
abdominal pain, and hemorrhage (each 2%). Fatal adverse
reactions occurred in 1.6% of patients who received TIVDAK,
including acute kidney injury, pneumonia, sepsis, and SJS (each
0.4%).
Adverse reactions leading to permanent discontinuation
occurred in 15% of patients receiving TIVDAK; the most common (≥3%)
were PN and ocular adverse reactions (each 6%). Adverse
reactions leading to dose interruption occurred in 39% of
patients receiving TIVDAK; the most common (≥3%) were ocular
adverse reactions (16%) and PN (6%). Adverse reactions leading
to dose reduction occurred in 30% of patients receiving TIVDAK;
the most common (≥3%) were PN and ocular adverse reactions (each
10%). The ocular adverse reactions included conjunctival disorders
(4.8%), keratopathy (4%), and dry eye (0.8%).
innovaTV 204 Study: 101 patients with r/mCC with disease
progression on or after chemotherapy
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, and hemorrhage (each 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%).
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.
Virtual mid- to late-stage pipeline update at ASCO
2024
On Monday, June 3, at 9:00 AM CDT (10:00 AM EDT/4:00 PM CEST),
Genmab will host a review of data presented at ASCO from its mid-
to late-stage pipeline. The event will be virtual and webcast live.
Details, including the webcast link and registration will be
available on www.genmab.com. This meeting is not an official
program of the ASCO Annual Meeting.
About Genmab
Genmab is an international biotechnology company with a core
purpose of guiding its unstoppable team to strive toward improving
the lives of patients with innovative and differentiated antibody
therapeutics. For 25 years, its passionate, innovative and
collaborative team has invented next-generation antibody technology
platforms and leveraged translational, quantitative and data
sciences, resulting in a proprietary pipeline including bispecific
T-cell engagers, antibody-drug conjugates, next-generation immune
checkpoint modulators and effector function-enhanced antibodies. 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 international presence across North America, Europe
and Asia Pacific. For more information, please visit Genmab.com and
follow us on LinkedIn and X.
About the Pfizer and Genmab Collaboration
Tisotumab vedotin is co-owned by Genmab and Pfizer, under an
agreement in which the companies share costs and profits for the
product on a 50:50 basis.
This Media Release 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 Media
Release 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 Pfizer Inc.
_____________________________ i Johnson, Daniel E., et al. “Head
and Neck Squamous Cell Carcinoma.” Nature Reviews Disease Primers,
Nature Publishing Group, 26 Nov. 2020,
https://www.nature.com/articles/s41572-020-00224-3#Fig2.
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David Freundel, Senior Director, Global Communications &
Corporate Affairs T: +1 609 430 2481; E: dafr@genmab.com Andrew
Carlsen, Vice President, Head of Investor Relations T: +45 3377
9558; E: acn@genmab.com
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