Results from MIRASOL Also Show ELAHERE is the First Treatment to
Demonstrate an Overall Survival Benefit in a Phase 3 Trial in
Platinum-Resistant Ovarian Cancer Compared to Chemotherapy
Clinically Meaningful Improvements in Progression Free Survival
and Overall Survival Observed with ELAHERE Regardless of Prior
Bevacizumab Status
Data Further Support Potential of ELAHERE to Become the New
Standard of Care for Patients with FRα-Positive Platinum-Resistant
Ovarian Cancer
MIRASOL Results to be Highlighted in Late-Breaking Oral
Presentation Today at ASCO Annual Meeting and Selected for the 2023
Best of ASCO Program®
ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field
of antibody-drug conjugates (ADCs) for the treatment of cancer,
today announced detailed results from 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 results are being
presented by Dr. Kathleen Moore in a late-breaking oral abstract
session today at the 2023 American Society of Clinical Oncology
(ASCO) Annual Meeting in Chicago, Illinois. These data have also
been selected for the 2023 Best of ASCO program, which will be held
this summer following the ASCO Annual Meeting.
"I am thrilled to share these impressive results from the
confirmatory MIRASOL trial at ASCO, which further demonstrate the
potential of ELAHERE to become the new standard of care for
patients with FRα-positive PROC," said Kathleen Moore, Associate
Director of Clinical Research and Director of the Oklahoma
TSET/Sarah Cannon Phase I Program, Professor of the Section of
Gynecologic Oncology at The University of Oklahoma and MIRASOL
Principal Investigator. "As we saw in the top-line data announced
last month, ELAHERE demonstrated an improvement versus chemotherapy
across all efficacy endpoints and, importantly, is the first
treatment to show an overall survival benefit in this patient
population. The 33% reduction in the risk of death, along with the
differentiated and well-characterized safety profile seen in
MIRASOL, reinforce the potential of ELAHERE to serve as a
transformative option for ovarian cancer patients and change how
this disease is treated."
MIRASOL is a randomized Phase 3 trial of ELAHERE versus
investigator's choice (IC) of single-agent chemotherapy (weekly
paclitaxel, pegylated liposomal doxorubicin, or topotecan).
Eligibility criteria include patients with PROC whose tumors
express high levels of FRα, using the Ventana FOLR1 Assay, and who
have been treated with up to three prior regimens. The primary
endpoint of this trial is progression-free survival (PFS) by
investigator assessment. Key secondary endpoints include objective
response rate (ORR) and overall survival (OS).
MIRASOL enrolled 453 patients. 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. As of the data cutoff on March 6, 2023, the
median follow-up time for OS was 13.1 months; 14% of patients on
the ELAHERE arm remained on study drug compared to 3% on the IC
chemotherapy arm.
- ELAHERE demonstrated a statistically significant and clinically
meaningful improvement in PFS by investigator assessment compared
to IC chemotherapy, with a hazard ratio (HR) of 0.65 (95%
confidence interval [CI]: 0.52, 0.81; p<0.0001), which
represents a 35% reduction in the risk of tumor progression or
death in the ELAHERE arm compared to the IC chemotherapy arm. The
median PFS in the ELAHERE arm was 5.62 months (95% CI: 4.34, 5.95)
compared to 3.98 months (95% CI: 2.86, 4.47) in the IC chemotherapy
arm.
- ELAHERE demonstrated a statistically significant and clinically
meaningful improvement in OS compared to IC chemotherapy. With 204
OS events reported as of March 6, 2023, the median OS was 16.46
months (95% CI: 14.46, 24.57) in the ELAHERE arm, compared to 12.75
months (95% CI: 10.91, 14.36) in the IC chemotherapy arm, with a HR
of 0.67 (95% CI: 0.50, 0.89; p=0.0046). This represents a 33%
reduction in the risk of death in the ELAHERE arm in comparison to
the IC chemotherapy arm.
- ORR by investigator assessment in the ELAHERE arm was 42.3%
(95% CI: 35.8%, 49.0%), including 12 complete responses (CRs),
compared to 15.9% (95% CI: 11.4%, 21.4%), with no CRs, in the IC
chemotherapy arm.
In addition to data on the primary and key secondary endpoints,
further safety and efficacy analyses from MIRASOL will be
presented:
- In the bevacizumab-naïve subset (n=172), the PFS HR was 0.66,
(95% CI: 0.46, 0.94; p=0.0210); in the bevacizumab-pretreated
subset (n=281), the PFS HR was 0.64 (95% CI: 0.49, 0.84;
p=0.0011).
- In the bevacizumab-naïve subset, the OS HR was 0.51 (95% CI:
0.31, 0.86; p=0.0099); in the bevacizumab-pretreated subset, the OS
HR was 0.74 (95% CI: 0.54, 1.04; p=0.0789).
- PFS and ORR results by blinded independent central review
(BICR) were concordant with investigator assessment.
- The HR for PFS by BICR was 0.72 (95% CI: 0.56, 0.92;
p=0.0082).
- ORR by BICR in the ELAHERE arm was 36.1% (95% CI: 29.9, 42.7),
including 16 complete responses (CRs), compared to 14.6% (95% CI:
10.3, 19.9), with 4 CRs, in the IC chemotherapy arm.
- ELAHERE was well-tolerated, consistent with the known safety
profile seen in the broader development program. No new safety
signals were identified in MIRASOL.
- Compared with IC chemotherapy, ELAHERE was associated with
lower rates of grade 3 or greater treatment-emergent adverse events
(TEAEs) (42% vs 54%) and serious adverse events (24% vs 33%).
- Dose delays due to TEAEs occurred in 54% of patients on both
arms; dose reductions due to TEAEs occurred in 34% of ELAHERE
treated patients vs 24% of IC chemotherapy patients;
discontinuations due to TEAEs occurred in 9% of ELAHERE treated
patients vs 16% of IC chemotherapy patients.
- The safety profile of ELAHERE consists of predominantly
low-grade ocular and gastrointestinal TEAEs.
- Detailed safety data will be presented, including rates of all
grade and grade 3+ ocular, gastrointestinal, neuropathy, and
hematologic TEAEs for ELAHERE vs IC chemotherapy (paclitaxel, PLD,
topotecan).
"We are incredibly pleased the MIRASOL results were selected as
a late-breaking presentation at ASCO," said Anna Berkenblit, MD,
Senior Vice President and Chief Medical Officer of ImmunoGen. "As
the first novel therapy to extend overall survival in
platinum-resistant disease, and with consistent efficacy regardless
of prior bevacizumab use, ELAHERE is a much-needed advance in the
ovarian cancer treatment paradigm. We look forward to submitting
the MAA and sBLA for ELAHERE in the EU and US, respectively, during
the second half of the year, and to progressing the broader ELAHERE
development program as we work to deliver this biomarker-directed
ADC to eligible patients."
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.
LATE-BREAKING ORAL PRESENTATION Title: Phase III MIRASOL
(GOG 3045/ENGOT-ov55) Study: Initial Report of Mirvetuximab
Soravtansine vs. Investigator's Choice of Chemotherapy in
Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary
Peritoneal, or Fallopian Tube Cancers with High Folate
Receptor-Alpha Expression Presenter: Dr. Kathleen Moore, Associate
Director of Clinical Research and Director of the Oklahoma
TSET/Sarah Cannon Phase I Program, Professor of the Section of
Gynecologic Oncology at The University of Oklahoma and MIRASOL
Principal Investigator Session: Late-Breaking Abstract Session:
Presentation and Discussion of LBA5507 Date: Sunday, June 4, 2023
Time: 7:30 am to 8:05 am CT / 8:30 am to 9:05 am ET
POSTER PRESENTATIONS ImmunoGen is also presenting two
trial-in-progress posters at ASCO.
Title: GLORIOSA: A Randomized, Open-Label, Phase 3 Study of
Mirvetuximab Soravtansine with Bevacizumab vs. Bevacizumab as
Maintenance in Platinum-Sensitive Ovarian, Fallopian Tube, or
Primary Peritoneal Cancer Presenter: Dr. David O'Malley, Professor,
Director of Gynecologic Oncology at the Ohio State University and
the James Cancer Center Abstract: TPS5622 Poster Board: 312a
Title: A Phase 1b/2 Study of Pivekimab Sunirine in Combination
with Venetoclax/Azacitidine or Magrolimab for Patients with
CD123-Positive Acute Myeloid Leukemia Presenter: Dr. Naval Daver,
Associate Professor in the Department of Leukemia at The University
of Texas MD Anderson Cancer Center Abstract: TPS7073 Poster Board:
203a
Additional information can be found at www.asco.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 standard of care in FRα-positive ovarian
cancer, to serve as a transformative option for ovarian cancer
patients and to change how this disease is treated; the potential
full approval of ELAHERE in the US and expansion to Europe,
including the submission of a MAA in Europe and a sBLA in the US
anticipated in the second half 2023; and the Company's business and
product development strategies. 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: top-line data
may change as more patient data become available and are subject to
audit and verification procedures; the timing and outcome of the
Company's preclinical and clinical development processes; the
results of the ongoing MIRASOL trial may not support full approval
of ELAHERE and, if so, additional studies may be required; the
difficulties inherent in the development of novel pharmaceuticals,
including uncertainties as to the timing, expense, and results of
preclinical studies, clinical trials, and regulatory processes; the
timing and outcome of the Company's 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 Report on Form 10-Q filed with the Securities and
Exchange Commission on April 28, 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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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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