Investigational Acasunlimab (DuoBody® -PD-L1x4-1BB) in Combination
with Pembrolizumab Demonstrates Meaningful Clinical Activity in
Phase 2 Trial in Patients with Previously Treated Metastatic
Non-small Cell Lung Cancer (mNSCLC)
- Initial data from the ongoing Phase 2 trial showed a
12-month overall survival rate of 69% and a median overall survival
of 17.5 months in patients with previously treated PD-L1-positive
metastatic non-small cell lung cancer treated with a combination of
acasunlimab and pembrolizumab every six weeks
- Data from this ongoing Phase 2 study to inform the planned
pivotal Phase 3 trial, which is expected to start before the end of
2024
COPENHAGEN, Denmark, and MAINZ, Germany,
June 1, 2024 — Genmab A/S (Nasdaq: GMAB, “Genmab”) and
BioNTech SE (Nasdaq: BNTX, “BioNTech”) today announced initial data
from the ongoing Phase 2 trial (NCT05117242) evaluating acasunlimab
(DuoBody-PD-L1x4-1BB), an investigational bispecific antibody also
known as GEN1046/BNT311, as monotherapy and in combination with
pembrolizumab in patients with PD-L(1)-positive metastatic
non-small cell lung cancer (“mNSCLC”) who had disease progression
following one or more prior lines of anti-PD(L)1-containing
treatment. The results showed a 12-month overall survival (“OS”)
rate of 69%, a median overall survival (“mOS”) of 17.5 months, and
a 30% overall response rate (“ORR”) (confirmed ORR 17%) at the time
of data cut-off in patients treated with the combination of
acasunlimab and pembrolizumab every six weeks. The findings were
presented at the 2024 American Society of Clinical Oncology
(“ASCO”) Annual Meeting held in Chicago, IL from May 31-June 4,
2024.
The Phase 2 study randomized a total of 113
patients in three arms, evaluating acasunlimab alone (Arm A) and in
combination with pembrolizumab (Arms B and C). The objective
response analysis was conducted for 62 centrally confirmed
PD-L1-positive efficacy-evaluable patients. The OS was evaluated in
all centrally confirmed PD-L1-positive patients (n=80). Arm A
showed a mOS rate of 5.5 months, a 50% disease control rate (DCR)
and a 31% ORR (confirmed ORR 13%) in patients treated with
acasunlimab alone. An 8.6 months mOS, a 59% DCR and a 21% ORR
(confirmed ORR 18%) for treatment of acasunlimab in combination
with pembrolizumab every three weeks (Arm B) and a 17.5 months mOS,
a 75% DCR and a 30% ORR (confirmed ORR 17%) when the combination
was administered every six weeks (Arm C). Anti-tumor activity was
observed in patients with a tumor proportion score (“TPS”) of 1–49%
and ≥50%, in patients with <6 months and ≥6 months of previous
immune checkpoint inhibitor (“CPI”) treatment, and in patients with
squamous and non-squamous histology.
Adverse events were consistent with the safety
profiles of the individual drugs and treatment related adverse
events (“TRAEs”) were primarily grade 1 and 2. The most common
TRAEs (all grades) in Arm A were asthenia (22.7%), diarrhea
(18.2%), nausea (18.2%), anemia (13.6%), and liver-related events
(13.6%). In the combination arms (Arms B and C), the most common
TRAEs were liver-related events (28.6%, 18.4%), fatigue (21.4%,
8.2%), asthenia (12%, 12.2%), and diarrhea (12%, 10.2%). Overall, a
lower incidence of grade ≥3 TRAEs, treatment-related liver-related
events and lower discontinuation rates were observed with the
combination regimen therapy administered every six weeks.
Transaminase elevations were generally asymptomatic and manageable
with the administration of steroids and/or treatment delay and
resolved more rapidly in patients treated with the combination
therapy administered every six weeks.
“We are encouraged by the findings of this
ongoing Phase 2 study. The initial results of acasunlimab in
combination with pembrolizumab administered every 6 weeks suggest a
potential meaningful impact on patients with metastatic non-small
cell lung cancer,” said Judith Klimovsky, Executive Vice
President & Chief Development Officer at Genmab. “We
will continue to evaluate these data to inform further development
of acasunlimab including a planned Phase 3 trial as we remain
committed to investigate acasunlimab as a potential treatment
option.”
“Most patients with mNSCLC have limited
treatment options following progression on first-line checkpoint
inhibitor therapy. For these patients, chemotherapy remains the
main treatment despite limited efficacy and considerable toxicity,”
said Prof. Özlem Türeci, M.D., Chief Medical Officer and
Co-Founder at BioNTech. “The data of our Phase 2 trial
show that the combination of acasunlimab with PDL1-blockade may be
a suitable approach in this heavily pretreated patient
population.”
About the GCT1046-04 Clinical Trial
The GCT1046-04 trial (NCT05117242) is a
randomized, open-label trial evaluating the safety and efficacy of
acasunlimab in patients with relapsed/refractory metastatic
non-small cell lung cancer (“mNSCLC”) after treatment with standard
of care therapy containing immune checkpoint inhibitor therapy.
Patients with stage IV NSCLC with at least one prior line of
systemic therapy containing an anti-PD-1/PD-L1 and a tumor PD-L1
expression in ≥1% of the tumor cells are included in the study. The
primary endpoint of the trial is the overall response rate (“ORR”).
Key secondary endpoints include overall survival (“OS”),
progression free survival (“PFS”), time to response (“TTR”),
duration of response (“DOR”), and safety. More information on this
trial can be found at clinicaltrials.gov.
About Non-small Cell Lung Cancer (NSCLC)
Non-small cell lung cancer (“NSCLC”) is the most
common type of lung cancer, accounting for about 85% of all
reported cases. NSCLC starts in cells that line the airways and can
grow into nearby tissues or spread to other parts of the body.
NSCLC is often diagnosed at an advanced stage, when it is hard to
treat and has a poor prognosis. The survival rate of patients with
NSCLC varies depending on the stage at
diagnosis.i,ii,iii,The treatment of NSCLC
depends on the stage, subtype, and biomarker status of the disease,
and may include surgery, radiation therapy, chemotherapy, targeted
therapy, immunotherapy, or a combination of these modalities.
About Acasunlimab
(GEN1046/BNT311)
Acasunlimab (GEN1046/BNT311) is an investigational PD-L1x4-1BB
bispecific antibody fusing Genmab's proprietary DuoBody®
technology platform and BioNTech’s proprietary immunomodulatory
antibodies. Acasunlimab is designed to elicit an antitumor response
via conditional activation of 4-1BB on T cells and natural killer
cells, which is strictly dependent on simultaneous binding of the
PD-L1 arm. Acasunlimab is being developed in collaboration by
BioNTech and Genmab under a license and collaboration agreement.
The candidate is currently being investigated in three clinical
trials: (1) a Phase 1/2 safety trial in patients with multiple
solid tumors, (2) a Phase 1 dose escalation trial in patients with
advanced solid tumors in Japan, and (3) a randomized Phase 2 safety
and efficacy trial with acasunlimab as a monotherapy and in
combination with pembrolizumab in patients with NSCLC who have
failed previous standard of care treatments with immune checkpoint
inhibitors. Please visit www.clinicaltrials.gov for more
information.
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.
Genmab Forward-Looking Statements
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 preclinical 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
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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™.
About BioNTech
Biopharmaceutical New Technologies (BioNTech) is
a global next generation immunotherapy company pioneering novel
therapies for cancer and other serious diseases. BioNTech exploits
a wide array of computational discovery and therapeutic drug
platforms for the rapid development of novel biopharmaceuticals.
Its broad portfolio of oncology product candidates includes
individualized and off-the-shelf mRNA-based therapies, innovative
chimeric antigen receptor (CAR) T cells, several protein-based
therapeutics, including bispecific immune checkpoint modulators,
targeted cancer antibodies and antibody-drug conjugate (ADC)
therapeutics, as well as small molecules. Based on its deep
expertise in mRNA vaccine development and in-house manufacturing
capabilities, BioNTech and its collaborators are developing
multiple mRNA vaccine candidates for a range of infectious diseases
alongside its diverse oncology pipeline. BioNTech has established a
broad set of relationships with multiple global and specialized
pharmaceutical collaborators, including Biotheus, DualityBio, Fosun
Pharma, Genentech, a member of the Roche Group, Genevant, Genmab,
MediLink, OncoC4, Pfizer and Regeneron.
For more information, please visit
www.BioNTech.com.
BioNTech Forward-Looking Statements
This press release contains forward-looking
statements within the meaning of the Private Securities Litigation
Reform Act of 1995, as amended, including, but not be limited to,
statements concerning: the collaboration between BioNTech and
Genmab to jointly clinical develop antibody candidates, including
GEN1046/BNT311 (acasunlimab); the timing of a pivotal Phase 3 trial
with GEN1046/BNT311 as well as any subsequent data readouts; the
registrational potential of any trial we may initiate for
GEN1046/BNT311; BioNTech’s current and future preclinical studies
and clinical trials in oncology, including GEN1046/BNT311 in
patients with mNSCLC; the nature and characterization of and timing
for release of clinical data across BioNTech’s platforms, which is
subject to peer review, regulatory review and market
interpretation; the planned next steps in BioNTech’s pipeline
programs, including, but not limited to, statements regarding
timing or plans for initiation or enrollment of clinical trials, or
submission for and receipt of product approvals and potential
commercialization with respect to BioNTech’s product candidates;
the ability of BioNTech’s mRNA technology to demonstrate clinical
efficacy outside of BioNTech’s infectious disease platform; and the
potential safety and efficacy of BioNTech’s product candidates. In
some cases, forward-looking statements can be identified by
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The forward-looking statements in this press
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because they involve known and unknown risks, uncertainties, and
other factors, many of which are beyond BioNTech’s control and
which could cause actual results to differ materially and adversely
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statements. These risks and uncertainties include, but are not
limited to: the uncertainties inherent in research and development,
including the ability to meet anticipated clinical endpoints,
commencement and/or completion dates for clinical trials,
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clinical data, including the data discussed in this release, and
including the possibility of unfavorable new preclinical, clinical
or safety data and further analyses of existing preclinical,
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subject to ongoing peer review, regulatory review and market
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in future clinical trials; the timing of and BioNTech’s ability to
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known to BioNTech at this time.
You should review the risks and uncertainties
described under the heading “Risk Factors” in BioNTech's Report on
Form 6-K for the period ended March 31, 2024 and in subsequent
filings made by BioNTech with the SEC, which are available on the
SEC’s website at www.sec.gov. These forward-looking statements
speak only as of the date hereof. Except as required by law,
BioNTech disclaims any intention or responsibility for updating or
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CONTACTS
Genmab
Media Contact
David Freundel
+1 609 430 2481
dafr@genmab.com
Investor Relations
Andrew Carlsen
+45 3377 9558
acn@genmab.com
BioNTech
Media Relations
Jasmina Alatovic
+49 (0)6131 9084 1513
media@biontech.de
Investor Relations
Victoria Meissner, M.D.
+1 617 528 8293
investors@biontech.de
i American Cancer Society. What is Non-Small Cell
Lung Cancer? https://www.cancer.org/cancer/types/lung-cancer.html.
Accessed May 14, 2024.
ii Mayo Clinic. Non-Small Cell Lung Cancer.
https://www.mayoclinic.org/diseases-conditions/lung-cancer/symptoms-causes/syc-20374620.
Accessed May 14, 2024.
iii CancerNet. Lung Cancer – Non-Small Cell:
Introduction.
https://www.cancer.net/cancer-types/lung-cancer-non-small-cell/introduction.
Accessed May 14, 2024.
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