Data Further Position ELAHERE to Become the New Standard of Care
for Patients with FRα-Positive Platinum-Resistant Ovarian
Cancer
Findings to be Highlighted in Oral Presentation at ESGO Annual
Congress
ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field
of antibody-drug conjugates (ADCs) for the treatment of cancer,
today announced findings from two subset analyses of the Phase 3
confirmatory MIRASOL trial (GOG 3045/ENGOT OV-55) evaluating the
safety and efficacy of ELAHERE® (mirvetuximab soravtansine-gynx)
compared to chemotherapy in patients with folate receptor alpha
(FRα)-positive platinum-resistant ovarian cancer (PROC). The
findings will be presented by Dr. Toon Van Gorp in an oral
presentation today at the 24th Congress of the European Society of
Gynaecological Oncology (ESGO) in Istanbul, Turkey.
“Consistent with the strong topline MIRASOL data where
superiority was seen across all efficacy endpoints, these subset
analyses show that the improvements in progression-free survival,
objective response rates, and overall survival demonstrated in the
overall study population are also observed regardless of the number
of prior lines of therapy,” said Toon Van Gorp, Professor of
Gynaecological Oncology at the University of Leuven. “Importantly,
the benefit seen with ELAHERE in patients treated with a prior PARP
inhibitor is particularly encouraging, as it has been shown that
PARP inhibitors have a potential negative impact on the efficacy of
subsequent chemotherapies. These new data being presented at ESGO,
including a consistent safety and tolerability profile, provide
valuable insights for physicians into ELAHERE’s broad and
meaningful benefit compared to chemotherapy and further position
ELAHERE to become the new standard of care for patients with
FRα-positive PROC.”
MIRASOL is a randomized Phase 3 trial of ELAHERE versus
investigator's choice (IC) of single-agent chemotherapy (weekly
paclitaxel, pegylated liposomal doxorubicin (PLD), or topotecan).
MIRASOL enrolled 453 patients with PROC, whose tumors express high
levels of FRα using what is now the Ventana FOLR1-2.1 assay, and
who have been treated with one to three prior regimens. Patients
were stratified by number of prior lines of therapy (14% had one
prior line of therapy, 40% had two prior lines of therapy, and 46%
had three prior lines of therapy) and by IC chemotherapy, with
paclitaxel as the most commonly chosen (41%), followed by PLD (36%)
and topotecan (23%). 62% of patients received prior bevacizumab;
55% received a prior PARP inhibitor. The primary endpoint of this
trial is progression-free survival (PFS) by investigator
assessment. Key secondary endpoints include objective response rate
(ORR), overall survival (OS), and patient-reported outcomes
(PROs).
EFFICACY OF MIRVETUXIMAB SORAVTANSINE IN FOLATE RECEPTOR
ALPHA HIGH, PLATINUM-RESISTANT OVARIAN CANCER BY TYPE AND NUMBER OF
PRIOR TREATMENT REGIMENS: AN EXPLORATORY ANALYSIS
Lead Author: Toon Van Gorp, MD
Date/Time: Thursday, September 28, 2023, 2:00-2:35pm TRT /
7:00-7:35am ET
Abstract: #1015 and #1056
In addition to the top-line MIRASOL data previously disclosed
and subsequently presented at the 2023 American Society of Clinical
Oncology (ASCO) Annual Meeting, the following new data are being
presented at ESGO:
- ELAHERE demonstrated clinically meaningful improvement in PFS
and ORR by investigator assessment and in OS compared to IC
chemotherapy, regardless of prior PARPi exposure.
- In patients with prior PARPi (n=251), PFS hazard ratio (HR) was
0.58 (95% CI: 0.43, 0.78; p= 0.0002); in the PARPi-naïve subset
(n=191), PFS HR was 0.74 (95% CI: 0.54, 1.03, p =0.0685).
- In patients with prior PARPi, ORR in the ELAHERE arm was 45%
(95% CI: 36%, 54%), including 7 CRs, compared to 17% (95% CI: 11%,
25%), with no CRs, in the IC chemotherapy arm (p<0.0001); in the
PARPi-naïve subset, ORR in the ELAHERE arm was 40% (95% CI: 30%,
51%), including 5 CRs, compared to 14% (95% CI: 8%, 23%), with no
CRs, in the IC chemotherapy arm (p<0.0001).
- In patients with prior PARPi, OS HR was 0.48 (95% CI: 0.33,
0.71; p= 0.0002); in the PARPi-naïve subset, OS HR was 0.90 (95%
CI: 0.590, 1.38, p =0.6319).
- ELAHERE demonstrated clinically meaningful improvements in PFS
and ORR by investigator assessment and in OS compared to IC
chemotherapy, regardless of prior lines of therapy (PLOT).
- In patients with 1 or 2 PLOT (n=245), the PFS HR was 0.61 (95%
CI: 0.45, 0.81; p=0.0007); in patients with 3 PLOT (n=208), PFS HR
was 0.71 (95% CI: 0.52, 0.98; p=0.0362).
- In patients with 1 or 2 PLOT, ORR in the ELAHERE arm was 46%
(95% CI: 37%, 55%), including 10 complete responses (CRs), compared
to 15% (95% CI: 9%, 22%), with no CRs, in the IC chemotherapy arm
(p<0.0001); in patients with 3 PLOT, ORR in the ELAHERE arm was
38% (95% CI: 29%, 48%), including 2 CRs, compared to 18% (95%
CI:11%, 26%), with no CRs, in the IC chemotherapy arm
(p=0.0009).
- In patients with 1 or 2 PLOT, OS HR was 0.66 (95% CI: 0.45,
0.98; p=0.0375); in patients with 3 PLOT, OS HR was 0.65 (95% CI:
0.43, 0.96; p=0.0308).
- ELAHERE demonstrated a tolerable safety profile compared to IC
chemotherapy consisting predominantly of low-grade ocular and
gastrointestinal events.
- In all patients, the frequency of grade 3+ treatment-emergent
adverse events (TEAEs) was 42% with ELAHERE and 54% with IC
chemotherapy; the frequency of serious adverse events (SAEs) was
24% with ELAHERE and 33% with IC chemotherapy; and the frequency of
discontinuations due to a TEAE was 9% with ELAHERE and 16% with IC
chemotherapy.
"Given ELAHERE is a potentially transformative option for those
with platinum-resistant ovarian cancer, it will be important for
clinicians to understand the consistency across these subset
analyses from MIRASOL as they make treatment decisions with their
patients," said Michael Vasconcelles, MD, ImmunoGen's Executive
Vice President, Research, Development, and Medical Affairs.
"Looking forward, we are excited to submit our MAA and sBLA to the
EMA and FDA, respectively, before year end while continuing to
advance our broader development program as we prioritize delivering
ELAHERE to eligible patients in need."
In November 2022, the US Food and Drug Administration (FDA)
granted accelerated approval for ELAHERE for the treatment of adult
patients with FRα-positive, platinum-resistant epithelial ovarian,
fallopian tube, or primary peritoneal cancer who have received one
to three prior systemic treatment regimens based on ORR and
duration of response data from the pivotal SORAYA trial.
Additional information can be found at
www.congress.esgo.org.
ABOUT OVARIAN CANCER
Ovarian cancer is the leading cause of death from gynecological
cancers in the US. Each year, roughly 20,000 patients are
diagnosed, and 13,000 patients will die. Most patients present with
late-stage disease and will typically undergo surgery followed by
platinum-based chemotherapy. Unfortunately, the majority of
patients eventually develop platinum-resistant disease, which is
difficult to treat. In this setting, standard of care single-agent
chemotherapies are associated with low response rates, short
durations of response, and significant toxicities.
ABOUT ELAHERE
ELAHERE (mirvetuximab soravtansine-gynx) is a first-in-class ADC
comprising a folate receptor alpha-binding antibody, cleavable
linker, and the maytansinoid payload DM4, a potent tubulin
inhibitor designed to kill the targeted cancer cells.
Indication and Usage
ELAHERE® is indicated for the treatment of adult patients with
folate receptor-alpha (FRα) positive, platinum-resistant epithelial
ovarian, fallopian tube, or primary peritoneal cancer, who have
received one to three prior systemic treatment regimens. Select
patients for therapy based on an FDA-approved test.
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 a confirmatory trial.
Important Safety Information
BOXED WARNING: OCULAR TOXICITY
- ELAHERE can cause severe ocular toxicities, including visual
impairment, keratopathy, dry eye, photophobia, eye pain, and
uveitis.
- Conduct an ophthalmic exam including visual acuity and slit
lamp exam prior to initiation of ELAHERE, every other cycle for the
first 8 cycles, and as clinically indicated.
- Administer prophylactic artificial tears and ophthalmic topical
steroids.
- Withhold ELAHERE for ocular toxicities until improvement and
resume at the same or reduced dose.
- Discontinue ELAHERE for Grade 4 ocular toxicities.
WARNINGS and PRECAUTIONS
Ocular Disorders
ELAHERE can cause severe ocular adverse reactions, including
visual impairment, keratopathy (corneal disorders), dry eye,
photophobia, eye pain, and uveitis.
Ocular adverse reactions occurred in 61% of patients with
ovarian cancer treated with ELAHERE. Nine percent (9%) of patients
experienced Grade 3 ocular adverse reactions, including visual
impairment, keratopathy/keratitis (corneal disorders), dry eye,
photophobia, and eye pain; and one patient (0.2%) experienced Grade
4 keratopathy. The most common (≥5%) ocular adverse reactions were
visual impairment (49%), keratopathy (36%), dry eye (26%), cataract
(15%), photophobia (13%), and eye pain (12%).
The median time to onset for first ocular adverse reaction was
1.2 months (range: 0.03 to 12.9). Of the patients who experienced
ocular events, 49% had complete resolution and 39% had partial
improvement (defined as a decrease in severity by one or more
grades from the worst grade) at last follow up. Ocular adverse
reactions led to permanent discontinuation of ELAHERE in 0.6% of
patients.
Premedication and use of lubricating and ophthalmic topical
steroids eye drops during treatment with ELAHERE are recommended.
Advise patients to avoid use of contact lenses during treatment
with ELAHERE unless directed by a healthcare provider.
Refer patients to an eye care professional for an ophthalmic
exam including visual acuity and slit lamp exam prior to treatment
initiation, every other cycle for the first 8 cycles, and as
clinically indicated. Promptly refer patients to an eye care
professional for any new or worsening ocular signs and
symptoms.
Monitor for ocular toxicity and withhold, reduce, or permanently
discontinue ELAHERE based on severity and persistence of ocular
adverse reactions.
Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease,
including pneumonitis, can occur in patients treated with ELAHERE.
Pneumonitis occurred in 10% of patients treated with ELAHERE,
including 0.8% with Grade 3 events, and 1 patient (0.2%) with a
Grade 4 event. One patient (0.2%) died due to respiratory failure
in the setting of pneumonitis and lung metastases.
Monitor patients for pulmonary signs and symptoms of
pneumonitis. Infectious, neoplastic, and other causes for symptoms
should be excluded through appropriate investigations.
Withhold ELAHERE for patients who develop persistent or
recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1
and consider dose reduction. Permanently discontinue ELAHERE in all
patients with Grade 3 or 4 pneumonitis. Patients who are
asymptomatic may continue dosing of ELAHERE with close
monitoring.
Peripheral Neuropathy (PN)
PN occurred in 36% of patients with ovarian cancer treated with
ELAHERE across clinical trials; 2% of patients experienced Grade 3
PN. PN adverse reactions included peripheral neuropathy (19%),
peripheral sensory neuropathy (9%), paraesthesia (6%),
neurotoxicity (3%), hypoaesthesia (2%), peripheral motor neuropathy
(1%), neuralgia (0.4%), polyneuropathy (0.2%) and oral hypoesthesia
(0.2%).
Monitor patients for signs and symptoms of neuropathy. For
patients experiencing new or worsening PN, withhold dosage, dose
reduce, or permanently discontinue ELAHERE based on the severity of
PN.
Embryo-Fetal Toxicity
Based on its mechanism of action, ELAHERE can cause embryo-fetal
harm when administered to a pregnant woman because it contains a
genotoxic compound (DM4) and affects actively dividing cells.
Advise pregnant women of the potential risk to a fetus. Advise
females of reproductive potential to use effective contraception
during treatment with ELAHERE and for 7 months after the last
dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in 31% of patients. The most
common (≥2%) serious adverse reactions were intestinal obstruction
(8%), ascites (4%), infection (3%), and pleural effusion (3%).
Fatal adverse reactions occurred in 2% of patients, including small
intestinal obstruction (1%) and pneumonitis (1%).
Permanent discontinuation of ELAHERE due to adverse reactions
occurred in 11% of patients. The most common (≥2%) adverse
reactions leading to permanent discontinuation were intestinal
obstruction (2%) and thrombocytopenia (2%). One patient (0.9%)
permanently discontinued ELAHERE due to visual impairment
(unilateral decrease to BCVA < 20/200 that resolved to baseline
after discontinuation).
Dosage delays of ELAHERE due to an adverse reaction occurred in
39% of patients. Adverse reactions which required dosage delays in
≥3% of patients included visual impairment (15%), keratopathy
(11%), neutropenia (6%), dry eye (5%), cataracts (3%) and increased
gamma-glutamyltransferase (3%).
Dose reductions of ELAHERE due to an adverse reaction occurred
in 20% of patients. Adverse reactions which required dose
reductions in ≥3% of patients included visual impairment (9%) and
keratopathy (7%).
The most common (≥20%) adverse reactions, including laboratory
abnormalities, were vision impairment, fatigue, increased aspartate
aminotransferase, nausea, increased alanine aminotransferase,
keratopathy, abdominal pain, decreased lymphocytes, peripheral
neuropathy, diarrhea, decreased albumin, constipation, increased
alkaline phosphatase, dry eye, decreased magnesium, decreased
leukocytes, decreased neutrophils, and decreased hemoglobin.
DRUG INTERACTIONS
Strong CYP3A4 Inhibitors
DM4 is a CYP3A4 substrate. Concomitant use of ELAHERE with
strong CYP3A4 inhibitors may increase unconjugated DM4 exposure,
which may increase the risk of ELAHERE adverse reactions. Closely
monitor patients for adverse reactions with ELAHERE when used
concomitantly with strong CYP3A4 inhibitors.
USE IN SPECIAL POPULATIONS
Lactation
Advise women not to breastfeed during treatment with ELAHERE and
for at least 1 month after the last dose.
Pediatric Use
Safety and effectiveness of ELAHERE have not been established in
pediatric patients.
Hepatic Impairment
Avoid use of ELAHERE in patients with moderate or severe hepatic
impairment (total bilirubin >1.5 ULN).
Please see full Prescribing Information, including Boxed Warning
for ELAHERE.
ABOUT IMMUNOGEN
ImmunoGen is developing the next generation of antibody-drug
conjugates (ADCs) to improve outcomes for cancer patients. By
generating targeted therapies with enhanced anti-tumor activity and
favorable tolerability profiles, we aim to disrupt the progression
of cancer and offer our patients more good days. We call this our
commitment to TARGET A BETTER NOW™.
Learn more about who we are, what we do, and how we do it at
www.immunogen.com.
ELAHERE® is a trademark of ImmunoGen, Inc.
FORWARD-LOOKING STATEMENTS
This press release includes forward-looking statements. These
statements include, but are not limited to, ImmunoGen's
expectations related to the potential of ELAHERE to become the new
standard of care for patients with FRα-positive platinum-resistant
ovarian cancer and to serve as a transformative option for
platinum-resistant ovarian cancer patients; and the timing and
outcome of the submissions of a Marketing Authorization Application
in Europe and a supplemental Biologics License Application in the
US. Various factors could cause ImmunoGen's actual results to
differ materially from those discussed or implied in the
forward-looking statements, and you are cautioned not to place
undue reliance on these forward-looking statements, which are
current only as of the date of this release. Factors that could
cause future results to differ materially from such expectations
include, but are not limited to: the successful execution of the
collaboration with Takeda and their development and
commercialization efforts; the timing and outcome of the Company's
clinical development processes; the difficulties inherent in the
development of novel pharmaceuticals, including uncertainties as to
the timing, expense, and results of clinical trials and regulatory
processes; the timing and outcome of anticipated interactions with
regulatory authorities; the risk that the Company may not be able
to obtain adequate price and reimbursement for any approved
products, including the potential for delays or additional
difficulties for ELAHERE in light of the FDA granting accelerated
approval; risks and uncertainties associated with the scale and
duration of the COVID-19 pandemic and the resulting impact on
ImmunoGen's industry and business; and other factors as set forth
in the Company's Annual Report on Form 10-K filed with the
Securities and Exchange Commission on March 1, 2023, the Company's
Quarterly Reports on Form 10-Q filed with the Securities and
Exchange Commission on April 28, 2023 and July 31, 2023, and other
reports filed with the Securities and Exchange Commission. The
forward-looking statements in this press release speak only as of
the date of this press release. ImmunoGen undertakes no obligation
to update any forward-looking statement, whether as a result of new
information, future developments, or otherwise, except as may be
required by applicable law.
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version on businesswire.com: https://www.businesswire.com/news/home/20230928394100/en/
INVESTOR RELATIONS ImmunoGen Anabel Chan 781-895-0600
anabel.chan@immunogen.com
MEDIA ImmunoGen Courtney O'Konek 781-895-0600
courtney.okonek@immunogen.com
OR
FTI Consulting Robert Stanislaro 212-850-5657
robert.stanislaro@fticonsulting.com
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