FORWARD I Did Not Meet Primary Endpoint of Progression-Free
Survival; Promising Efficacy Results Seen in Folate Receptor Alpha
(FRα) High Patients
Favorable Tolerability and Differentiated Safety Profile
Observed with Mirvetuximab Monotherapy Compared to Chemotherapy
Exploratory Analyses Demonstrate Improved Efficacy Outcomes in
FRα High Patients
Registration Study for Mirvetuximab in Ovarian Cancer on Track
to Start by Year-End
Conference Call to be Held Monday, September 30 at 8:00 a.m.
ET
ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field
of antibody-drug conjugates (ADCs) for the treatment of cancer,
today announced full data and additional exploratory analyses from
the Phase 3 FORWARD I study evaluating mirvetuximab soravtansine
compared to chemotherapy in women with folate receptor alpha
(FRα)-positive, platinum-resistant ovarian cancer during an oral
presentation at the European Society for Medical Oncology (ESMO)
2019 Congress in Barcelona, Spain.
“While it is disappointing that FORWARD I did not meet the
primary endpoint of progression-free survival, mirvetuximab
demonstrated consistent and meaningful efficacy signals in patients
with high levels of FRα expression and was well tolerated with a
differentiated safety profile in both the ITT and FRα high
populations,” said Dr. Kathleen Moore, Associate Director of
Clinical Research at the Stephenson Cancer Center at the University
of Oklahoma. “Despite recently reported advances in frontline
treatment with the addition of PARPi maintenance therapy, the
majority of patients will unfortunately develop platinum-resistant
disease with limited therapeutic options characterized by low
response rates, short progression-free survival, and significant
toxicities. The encouraging data from FORWARD I suggest the
potential for a significant improvement over single-agent
chemotherapy in the FRα high population and I look forward to the
continued development of mirvetuximab for these patients in the
upcoming Phase 3 study.”
The FORWARD I Phase 3 trial randomized 366 patients 2:1 to
receive either mirvetuximab or the physician's choice of
single-agent chemotherapy (pegylated liposomal doxorubicin,
topotecan, or weekly paclitaxel). Eligibility criteria included
patients with platinum-resistant ovarian cancer that expressed
medium or high levels of FRα, who had been treated with up to three
prior regimens. The primary endpoint of this study was
progression-free survival (PFS), which was assessed using the
Hochberg procedure in the entire study population and in the subset
of patients with high FRα expression. The Hochberg procedure
enables the simultaneous testing of two overlapping populations.
Under this statistical analysis plan, if the p-value of the primary
endpoint in either population is greater than 0.05, the p-value in
the other population needs to be less than or equal to 0.025 to
achieve statistical significance.
Key Findings from the Phase 3 FORWARD I Study
- In the entire study population, the confirmed overall response
rate (ORR) was higher for mirvetuximab than for chemotherapy (22%
vs 12%, p-value 0.015), without a significant difference in the
primary endpoint of PFS (HR 0.981, p-value 0.897) or overall
survival (OS) (HR 0.815, p-value 0.248).
- In the pre-specified FRα high subgroup (218/366, 60%):
- Median PFS (mPFS) was longer in patients who received
mirvetuximab compared with chemotherapy (4.8 months vs 3.3 months,
HR 0.693, p-value 0.049). Given that the p-value in the entire
study population exceeded 0.05, the statistical analysis plan for
the study required the p-value in the high subset to be less than
or equal to 0.025 to achieve statistical significance.
- Confirmed ORR was higher for mirvetuximab than for chemotherapy
(24% vs 10%, p-value 0.014).
- OS was longer in patients who received mirvetuximab compared
with chemotherapy (HR 0.618, p-value 0.033).
- The trend in improved OS in patients who received mirvetuximab
compared with chemotherapy persisted with an additional 6 months of
follow-up (updated through August 2019: HR 0.678, with median OS
[mOS] 16.4 months vs 12.0 months, p-value 0.048).
- Mirvetuximab was well-tolerated, with fewer patients
experiencing grade 3 or greater treatment emergent adverse events
(TEAEs) (46% vs 61%), fewer dose reductions (20% vs 31%), and fewer
discontinuations due to drug-related TEAEs (5% vs 8%) compared with
chemotherapy.
- The safety profile of mirvetuximab was confirmed, with the most
common drug-related adverse events including nausea (46% all
grades; 1% grade 3 or greater), blurred vision (42% all grades; 2%
grade 3 or greater), and keratopathy (33% all grades; 1% grade 3 or
greater).
- Over twice the percentage of patients who received mirvetuximab
compared with chemotherapy reported improved quality of life, as
measured by at least a 15-point improvement in the abdominal/GI
symptom subscale of the EORTC-QLQ OV28 (32% vs 14%).
Exploratory Analyses “While FORWARD I generated promising
outcomes in the FRα high subgroup, the anti-tumor activity did not
reach the levels we have observed in our previous studies with
mirvetuximab. Accordingly, we have undertaken a comprehensive
assessment of the factors that may have contributed to the outcomes
in FORWARD I. These exploratory analyses demonstrate that the use
of a simplified scoring method to assess tumor samples for FRα
expression inadvertently introduced a population of patients into
FORWARD I with lower levels of FRα than intended,” said Anna
Berkenblit, M.D., Senior Vice President and Chief Medical Officer
of ImmunoGen. “When we reassessed the FORWARD I tumor samples using
the scoring method from our previous studies, we determined that a
significant percentage of patients included in FORWARD I had low
levels of FRα expression that should have precluded enrollment. For
those patients with medium or high levels of FRα expression upon
rescoring, we observed efficacy outcomes for mirvetuximab much more
in line with our previous experience, with improved activity
correlating with FRα expression and the strongest treatment effect
for all efficacy endpoints in the intended FRα high patient
population. These findings have informed the design of our planned
Phase 3 registration trial in FRα high patients.”
Previous studies with mirvetuximab have used a PS2+ scoring
method to assess tumor samples for FRα expression to determine
eligibility. The PS2+ scoring method assesses both intensity of
staining (0, 1+, 2+, or 3+) and percentage of tumor cells staining
at each intensity, with at least 50% of cells with at least 2+
staining considered FRα medium and at least 75% of cells with at
least 2+ staining considered FRα high.
In preparation for launch of a companion diagnostic for
commercial use, a simplified scoring method to assess FRα
expression, known as 10X, was implemented prior to the start of
FORWARD I. Eligibility was determined by scoring the percentage of
tumor cells with positive membrane staining by ≤10X magnification
without the need to separately assess level of intensity. A
bridging study indicated that the 10X scoring method was sufficient
for patient selection: staining visible at ≤10X magnification
correlated with higher intensity staining (2+ and 3+), with lower
intensity staining visible only at higher magnification.
Comparison to the much larger dataset from patients enrolled in
FORWARD I, however, suggested a significant population shift
towards increased prevalence of FRα expression under the 10X
scoring method as compared to the PS2+ scoring method. Rescoring of
the FORWARD I tumor samples by an independent pathologist, blinded
to treatment assignment, using the PS2+ method demonstrated that
34% of patients enrolled in FORWARD I had FRα expression below the
intended level. In addition, the FRα high subset enrolled in the
study also contained a mixture of FRα expression when scored using
the PS2+ method.
Key Findings from Exploratory PS2+ Scoring for FRα Determination
in Phase 3 FORWARD Study Exploratory efficacy analyses of the
FORWARD I patients scored using the PS2+ method demonstrate
improved outcomes correlated with FRα expression, with the
strongest treatment effects for all efficacy endpoints in the PS2+
FRα high population (n=116). Compared with chemotherapy,
mirvetuximab was associated with:
- Longer PFS (mPFS 5.6 months vs 3.2 months, HR 0.549 [95% CI
0.336, 0.897]);
- Higher confirmed ORR (29% vs 6%); and
- Longer OS (updated through August 2019: mOS 16.4 months vs 11.4
months, HR 0.678 [95% CI 0.410, 1.119]).
“With the results of these exploratory analyses, we have
developed a clear view of which patients benefit most from
mirvetuximab and how to best identify those patients,” said Mark
Enyedy, ImmunoGen’s President and Chief Executive Officer. “We are
working closely with FDA to finalize the design of a Phase 3
registration trial for mirvetuximab, which we call MIRASOL, and
believe that the robust data generated from the FORWARD I analyses
increase the likelihood of a positive outcome with this next study.
We anticipate enrolling the first patient by the end of the year
with topline readout in the first half of 2022.”
ESMO Oral Presentation Details
- Title: “FORWARD I (GOG 3011): A Phase III study of
mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting
antibody-drug conjugate (ADC), versus chemotherapy in patients
(pts) with platinum-resistant ovarian cancer (PROC)” (Abstract
#992O)
- Date: Sunday, September 29, 2019
- Time: 8:30 a.m. CEST/2:30 a.m. ET
- Lead Author: Kathleen Moore M.D., University of Oklahoma
Health Sciences Center, Oklahoma City, OK
Additional information can be found at www.esmo.org.
CONFERENCE CALL INFORMATION ImmunoGen will host a
conference call on Monday, September 30, 2019 at 8:00 a.m. ET to
discuss the complete findings from FORWARD I. Access the call using
the information below.
PHONE US Toll-Free: (877) 621-5803 Spain
Toll-Free: 900971520 Barcelona Local: 0934923253 International:
(470) 495-9491 Conference ID: 8295336
SLIDES/WEBCAST Link:
https://edge.media-server.com/mmc/p/jwvdobji
ABOUT MIRVETUXIMAB SORAVTANSINE Mirvetuximab soravtansine
(IMGN853) is the first folate receptor alpha (FRα)-targeting ADC.
It uses a humanized FRα-binding antibody to target the ADC
specifically to FRα-expressing cancer cells and a potent anti-tumor
agent, DM4, to kill the targeted cancer cells.
ABOUT FORWARD I FORWARD I is a Phase 3 trial in which 366
patients were randomized 2:1 to receive either mirvetuximab
soravtansine or the physician's choice of single-agent chemotherapy
(pegylated liposomal doxorubicin, topotecan, or weekly paclitaxel).
Eligible patients were diagnosed with platinum-resistant ovarian
cancer that expresses medium or high levels of folate receptor
alpha (FRα) and were treated with up to three prior regimens. The
primary endpoint of this study was progression free survival (PFS),
which was assessed in the entire study population and in the subset
of patients with high FRα expression. ImmunoGen estimates that
12,000-14,000 patients per year in the U.S. meet these criteria,
with a comparable number in the major markets in Europe.
ImmunoGen partnered with the GOG Foundation Inc., a leader in
clinical research in gynecologic malignancies, on FORWARD I, which
was conducted in North America and Europe.
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.
This press release includes forward-looking statements regarding
ImmunoGen’s expectations related to: the design and potential
success of ImmunoGen’s future mirvetuximab soravtansine studies and
regulatory pathway, including the timing of initiating and
receiving data from, as well as the likelihood of success of, the
planned registration study of mirvetuximab. For these statements,
ImmunoGen claims the protection of the safe harbor for
forward-looking statements provided by the Private Securities
Litigation Reform Act of 1995. 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 timing and
results of communications with FDA, risks and uncertainties related
to the execution of the restructuring of the Company’s operations,
the Company’s ability to control future spending and obtain
additional funds to enable it to fund its continuing operations
through the release of top-line results from the planned
mirvetuximab pivotal study, the possibility that future studies
fail to replicate the data indicated in the exploratory analyses of
the FORWARD 1 data, and the risks and uncertainties inherent in the
Company’s development programs, including clinical studies and
regulatory processes, their timings and results. A review of these
risks can be found under the heading “Risk Factors” in ImmunoGen’s
Annual Report on Form 10-K for the year ended December 31, 2018 and
subsequent documents filed with the Securities and Exchange
Commission.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20190928005004/en/
INVESTOR RELATIONS AND MEDIA ImmunoGen Courtney O’Konek
781-895-0600 courtney.okonek@immunogen.com OR FTI Consulting
Robert Stanislaro 212-850-5657
robert.stanislaro@fticonsulting.com
ImmunoGen (NASDAQ:IMGN)
Historical Stock Chart
From Mar 2024 to Apr 2024
ImmunoGen (NASDAQ:IMGN)
Historical Stock Chart
From Apr 2023 to Apr 2024