- Preliminary analysis of data from the EPCORE™ NHL-2 study
demonstrates patients with previously untreated follicular lymphoma
(FL) who received epcoritamab in combination with
rituximab-lenalidomide (R2) experienced a 95% overall response rate
(ORR)
- Results from the optimization cohort of the EPCORE™ NHL- 1
study show that mitigation strategies led to a clinically
significant reduction in rate of cytokine release syndrome (CRS)
and immune effector cell-associated neurotoxicity syndrome (ICANS)
in patients with relapsed/refractory (R/R) FL treated with
epcoritamab
Genmab A/S (Nasdaq: GMAB) today announced new
efficacy and safety data from two ongoing Phase 1/2 clinical trials
evaluating epcoritamab, a T-cell engaging bispecific antibody
administered subcutaneously, in adult patients with certain types
of follicular lymphoma (FL). A preliminary analysis of data from
the EPCORE™ NHL-2 study (NCT04663347), evaluating epcoritamab in
combination with rituximab-lenalidomide (R2), demonstrated an
overall response rate (ORR) of 95% and complete response rate (CRR)
of 85% in patients with previously untreated FL. The safety and
efficacy for this use have not been established. The data were
shared during a rapid oral presentation (Abstract #7014) at the
2024 American Society of Clinical Oncology (ASCO) Annual Meeting,
being held in Chicago, IL and virtually, May 31-June 4, 2024.
Separately, new data from the cycle 1 optimization part (C1 OPT)
of the EPCORE™ NHL-1 study (NCT03625037), evaluating epcoritamab in
patients with relapsed/refractory (R/R) FL, showed that following
additional mitigation strategies, cytokine release syndrome (CRS)
(any grade) was reported in 49 percent of patients vs. 66 percent
of patients (any grade) in the pivotal cohort. Additionally, there
were no Grade 3 or higher CRS events and no reported immune
effector cell-associated neurotoxicity syndrome (ICANS). CRS and
ICANS are adverse reactions, which can be serious and/or life
threatening. Patients need to be monitored and carefully managed
per current practice guidelines. These results (Abstract #7015)
were selected to be a part of Best of ASCO® (July 19-20 in Boston,
MA), which features the most impactful research from the 2024 ASCO
Annual Meeting.
FL is the second most common form of non-Hodgkin’s lymphoma
(NHL), accounting for 20-30 percent of all NHL cases.i About 15,000
people develop FL each year in the U.S.ii FL is considered
incurable with current standard of care therapies and patients
often relapse.iii,iv With each subsequent line of therapy, patients
receiving currently available treatments may experience shorter
durability of remission.v
“Follicular lymphoma is considered incurable and patients at all
stages of disease need innovative treatment options. Our data at
this year’s ASCO suggest that epcoritamab can potentially provide
promising overall and complete responses for patients with
follicular lymphoma, whether previously untreated or post-relapse.
Importantly, we’ve also focused on reducing incidence of CRS and
ICANS through optimizing dosing safety of epcoritamab for patients
with relapsed/refractory disease,” said Judith Klimovsky, Executive
Vice President & Chief Development Officer, Genmab. “These data
reflect our efforts, alongside our partner AbbVie, to continue the
development of epcoritamab as a potential core therapy across
B-cell malignancies.”
EPCORE™ NHL-2 Results in First-Line FL (Abstract
#7014)
The EPCORE NHL-2 study analysis included results from two arms
of the study. Arm 6 evaluated epcoritamab in combination with R2 in
patients with previously untreated FL (n=41). With a median
follow-up of 21.1 months, additional findings from this arm showed
durable responses, with an estimated 89 percent of patients
remaining progression free and 93 percent of patients who had
achieved a CR remaining in CR at 18 months.
“The results from this preliminary analysis of epcoritamab in
combination with rituximab-lenalidomide as a first-line,
chemotherapy-free treatment for patients with FL are encouraging
and support the continued evaluation of epcoritamab in this patient
population,” said Joshua Brody, MD, Director, Lymphoma
Immunotherapy Program Icahn School of Medicine at Mount Sinai Hess
Center for Science and Medicine.
The most common treatment-emergent adverse events (TEAEs) in
these first-line patients were COVID-19 (63 percent), CRS (56
percent) and neutropenia (56 percent). All CRS events were low
grade (41 percent Grade 1 and 15 percent Grade 2) and resolved.
Most CRS events occurred after patients received their first full
dose of epcoritamab, and none led to treatment discontinuation. Two
fatal TEAEs occurred due to COVID-19 pneumonia and septic
shock.
The EPCORE NHL-2 study results also included the first data
disclosure from arm 7, which evaluated epcoritamab administered
every 8 weeks for patients with first- or second-line FL in CR or
partial response (PR) following standard-of-care treatment (n=20).
Median follow-up was 19.7 months. An estimated 90 percent of
patients remained alive at 21 months. Notably, 100 percent of
patients who entered the arm with a PR converted to a CR (n=8).
In arm 7, the most common TEAEs were COVID-19 (70 percent) and
CRS (55 percent). Only one CRS event (Grade 1) occurred during Q8W
maintenance dosing. All other CRS events were during cycle 1 (C1)
step-up dosing, as expected for these patients who had not
previously received epcoritamab. One fatal TEAE occurred related to
respiratory failure caused by post-acute COVID syndrome.
EPCORE™ NHL-1 Data in Later-line FL (Abstract
#7015)
In this C1 optimization cohort in patients with R/R FL, patients
received epcoritamab in 3 step-up doses (0.16, 0.8, and 3 mg),
along with dexamethasone prophylaxis and hydration recommendations
followed by full 48-mg doses until disease progression or
unacceptable toxicity. There was no mandatory hospitalization. With
a median follow-up of 5.7 months, CRS rate was 49% (Grade 1 40%,
Grade 2 9%), primarily occurring during cycle 1, and all events
resolved. CRS was adequately identified in the outpatient setting
and appropriately treated. There were no ICANS events.
These findings show that mitigation measures implemented early
in the epcoritamab treatment cycle may lead to substantial
improvements in the incidence and severity of CRS and ICANS.
Further, among the 81 response-evaluable patients in the cohort,
ORR was 91 percent and CR rate was 68 percent, suggesting that the
additional CRS mitigation did not impact efficacy.
On February 26, 2024, the U.S. Food and Drug Administration
(FDA) granted Priority Review for the supplemental Biologics
License Application (sBLA) for epcoritamab-bysp for the treatment
of adult patients with relapsed or refractory (R/R) follicular
lymphoma (FL) after two or more lines of systemic therapy. Use of
epcoritamab in FL is not approved in the U.S. or in the EU or in
any other territory. The safety and efficacy of epcoritamab for use
in FL have not been established.
About the EPCORE™ NHL-2 Trial
EPCORE™ NHL-2 is a phase 1b/2, open-label, multinational,
interventional trial to evaluate the safety, and preliminary
efficacy of epcoritamab in combination with standard of care agents
in patients with B-cell non-Hodgkin’s lymphoma, including FL, and
across multiple lines of therapy. The trial consists of two parts –
Part 1 (dose escalation) and Part 2 (dose expansion) – and 10
different treatment arms. The primary objective of Part 1 is
safety, and it includes arm 1-5 and arm 10. Part 2 includes all 10
arms (arm 1-10) with the objective of preliminary efficacy.
However, the primary objective of arm 7 is safety. More information
on this trial be found at https://www.clinicaltrials.gov/ (NCT:
04663347).
About the EPCORE™ NHL-1 Trial
EPCORE™ NHL-1 is an open-label, multi-center safety and
preliminary efficacy trial of epcoritamab that consists of three
parts: a dose escalation part; an expansion part; and an
optimization part. The trial was designed to evaluate subcutaneous
epcoritamab in patients with relapsed or refractory B-cell
non-Hodgkin’s lymphoma (B-NHL), including FL. In the expansion
part, additional patients were enrolled to further explore the
safety and efficacy of epcoritamab in three cohorts of patients
with different types of relapsed/refractory B-NHLs who have limited
therapeutic options and generated pivotal data for patients with FL
and diffuse large B-cell lymphoma (DLBCL). The optimization part
evaluated additional cytokine release syndrome (CRS) mitigation
strategies during cycle 1. The primary endpoint of the expansion
part was ORR as assessed by an IRC. Secondary efficacy endpoints
included duration of response, complete response rate, duration of
complete response, progression-free survival, and time to response
as determined by the Lugano criteria. Overall survival, time to
next therapy, and rate of minimal residual disease negativity were
also evaluated as secondary efficacy endpoints. The primary
endpoint of the optimization part was the rate of ≥ Grade 2 CRS
events and all grade CRS events from first dose of epcoritamab
through 7 days following administration of the second full dose of
epcoritamab.
About Follicular Lymphoma (FL)
FL is typically an indolent (or slow-growing) form of
non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.vi FL
is the second most common form of NHL overall, accounting for 20-30
percent of all NHL cases, and represents 10-20 percent of all
lymphomas in the western world.i,vii Although FL is an indolent
lymphoma, it is considered incurable with conventional therapy and
patients who achieve remission also often experience
relapse.iii,iv,viii Additionally, with each relapse the remission
and time to next treatment is shorterix, adding increased cost to
the health system and negatively impacting the patient's quality of
life.x
About Epcoritamab
Epcoritamab is an IgG1-bispecific antibody created using
Genmab's proprietary DuoBody® technology and administered
subcutaneously. Genmab's DuoBody-CD3 technology is designed to
direct cytotoxic T cells selectively to elicit an immune response
toward target cell types. Epcoritamab is designed to simultaneously
bind to CD3 on T cells and CD20 on B cells and induces
T-cell-mediated killing of CD20+ cells.xi
Epcoritamab (approved under the brand name EPKINLY in the U.S.
and Japan, and TEPKINLY in the EU) has received regulatory approval
in certain lymphoma indications in several territories. Use of
epcoritamab in FL is not approved in the U.S. or in the EU or in
any other territory. Epcoritamab is being co-developed by Genmab
and AbbVie as part of the companies' oncology collaboration. The
companies will share commercial responsibilities in the U.S. and
Japan, with AbbVie responsible for further global
commercialization.
Genmab and AbbVie continue to evaluate the use of epcoritamab as
a monotherapy, and in combination, across lines of therapy in a
range of hematologic malignancies. This includes four ongoing phase
3, open-label, randomized trials including a trial evaluating
epcoritamab as a monotherapy in patients with R/R DLBCL compared to
investigators choice chemotherapy (NCT: 04628494), a trial
evaluating epcoritamab in combination with R-CHOP in adult
participants with newly diagnosed DLBCL (NCT: 05578976), a trial
evaluating epcoritamab in combination with rituximab and
lenalidomide (R2) in patients with R/R FL (NCT: 05409066), and a
trial evaluating epcoritamab in combination with R2 compared to
chemoimmunotherapy in patients with previously untreated FL (NCT:
06191744). The safety and efficacy of epcoritamab has not been
established for these investigational uses. Please visit
clinicaltrials.gov for more information.
EPKINLY® (epcoritamab-bysp) U.S. IMPORTANT SAFETY
INFORMATION
Important Warnings—EPKINLY can cause serious side effects,
including:
- Cytokine release syndrome (CRS), which is common during
treatment with EPKINLY and can be serious or life-threatening. To
help reduce your risk of CRS, you may receive other medicines
before receiving EPKINLY and you will also be given smaller doses
of EPKINLY for the first 2 doses (called “step-up” dosing). Your
first full dose of EPKINLY will be given on day 15 of your first
cycle of treatment and you should be hospitalized for 24 hours
after due to risk of CRS and neurologic problems. If your dose of
EPKINLY is delayed for any reason, you may need to repeat the
step-up dosing schedule.
- Neurologic problems that can be life-threatening and
lead to death. Neurologic problems may happen days or weeks after
you receive EPKINLY.
Tell your healthcare provider or get medical help right
away if you develop a fever of 100.4°F (38°C) or higher;
dizziness or lightheadedness; trouble breathing; chills; fast
heartbeat; feeling anxious; headache; confusion; shaking (tremors);
problems with balance and movement, such as trouble walking;
trouble speaking or writing; confusion and disorientation;
drowsiness, tiredness or lack of energy; muscle weakness; seizures;
or memory loss. These may be symptoms of CRS or neurologic
problems. Do not drive or use heavy machinery or do other
dangerous activities if you have any symptoms that impair
consciousness until your symptoms go away.
EPKINLY can cause other serious side effects,
including:
- Infections that may lead to death. Tell your healthcare
provider right away if you develop any symptoms of infection during
treatment, including fever of 100.4°F (38°C) or higher, cough,
chest pain, tiredness, shortness of breath, painful rash, sore
throat, pain during urination, or feeling weak or generally
unwell.
- Low blood cell counts are common during treatment with
EPKINLY and can be serious or severe. Your healthcare provider will
check your blood cell counts during treatment. EPKINLY may cause
low blood cell counts, including low white blood cells
(neutropenia), which can increase your risk for infection; low red
blood cells (anemia), which can cause tiredness and shortness of
breath; and low platelets (thrombocytopenia), which can cause
bruising or bleeding problems.
Your healthcare provider will monitor you for symptoms of CRS,
neurologic problems, infections, and low blood cell counts during
treatment with EPKINLY. Your healthcare provider may temporarily
stop or completely stop treatment with EPKINLY if you develop
certain side effects.
Before you receive EPKINLY, tell your healthcare provider
about all your medical conditions, including if you have an
infection, are pregnant or plan to become pregnant, or are
breastfeeding or plan to breastfeed. If you receive EPKINLY while
pregnant, it may harm your unborn baby. If you are a female who
can become pregnant, your healthcare provider should do a
pregnancy test before you start treatment with EPKINLY and you
should use effective birth control (contraception) during treatment
and for 4 months after your last dose of EPKINLY. Tell your
healthcare provider if you become pregnant or think that you may be
pregnant during treatment with EPKINLY. Do not breastfeed during
treatment with EPKINLY and for 4 months after your last dose of
EPKINLY.
The most common side effects of EPKINLY include CRS,
tiredness, muscle and bone pain, injection site reactions, fever,
stomach-area (abdominal) pain, nausea, and diarrhea. These are not
all the possible side effects of EPKINLY. Call your doctor for
medical advice about side effects.
You are encouraged to report side effects to the FDA at (800)
FDA-1088 or www.fda.gov/medwatch or to Genmab US, Inc. at
1-855-4GENMAB (1-855-443-6622).
Please see Medication Guide, including Important Warnings.
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.
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™. EPCORE™, EPKINLY®, TEPKINLY® and their designs
are trademarks of AbbVie Biotechnology Ltd.
________________________________ i Ma S. Risk factors of
follicular lymphoma. Expert Opin Med Diagn. 2012;6:3232333. doi:
10.1517/17530059.2012.686996. ii Leukemia & Lymphoma Society.
https://www.lls.org/research/follicular-lymphoma-fl. Accessed March
2024. iii Link BK, et al. Second-Line and Subsequent Therapy and
Outcomes for Follicular Lymphoma in the United States: Data From
the Observational National LymphoCare Study. Br J Haematol
2019;184(4):660-663. iv Ren J, et al. Economic Burden and Treatment
Patterns for Patients With Diffuse Large B-Cell Lymphoma and
Follicular Lymphoma in the USA. J Comp Eff Res 2019;8(6):393-402. v
Ghione P, Palomba ML, Ghesquieres H, et al. Treatment patterns and
outcomes in relapsed/refractory follicular lymphoma: results from
the international SCHOLAR-5 study. Haematologica.
2023;108(3):822-832. doi: 10.3324/haematol.2022.281421. vi Lymphoma
Research Foundation official website.
https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed February 2024.
vii Luminari S, Bellei M, Biasoli I, Federico M. Follicular
lymphoma—treatment and prognostic factors. Rev Bras Hematol
Hemoter. 2012;34:54-59. doi: 10.5581/1516-8484.20120015. viii
Lymphoma Research Foundation official website.
https://lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/follicular-lymphoma/relapsedfl/.
Accessed February 2024. ix Rivas‐Delgado, A., Magnano, L.,
Moreno‐Velázquez, et al. Response duration and survival shorten
after each relapse in patients with follicular lymphoma treated in
the rituximab era. Br J Haematol. 2018;184(5):753-759.
doi:10.1111/bjh.15708 x Kuruvilla J, Ewara EM, Elia-Pacitti J, et
al. Estimating the Burden of Illness of Relapsed Follicular
Lymphoma and Marginal Zone Lymphoma in Ontario, Canada. Curr Oncol.
2023;30(5):4663-4676. doi:10.3390/curroncol30050352 xi Engelberts
PJ, Hiemstra IH, de Jong B, et al. DuoBody-CD3xCD20 induces potent
T-cell-mediated killing of malignant B cells in preclinical models
and provides opportunities for subcutaneous dosing. EBioMedicine.
2020;52:102625. doi: 10.1016/j.ebiom.2019.102625.
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