Genmab A/S (Nasdaq: GMAB):
- Preliminary analyses from the EPCORE® CLL-1 trial
demonstrates overall response rate (ORR) of 61 percent and complete
response (CR) rate of 39 percent in heavily pretreated patients
with relapsed or refractory (R/R) chronic lymphocytic leukemia
(CLL) who received epcoritamab monotherapy
- In the study, 75 percent of evaluable responders achieved
undetectable minimal residual disease (MRD), indicating no
detectable disease following treatment with epcoritamab
- The data were selected as part of the 2024 American Society
of Hematology’s (ASH’s) Annual Meeting Press Program in the
Diagnosing and Treating Blood Cancers and “Almost Cancers”
briefing
Genmab A/S (Nasdaq: GMAB) today announced results
from the Phase 1b/2 EPCORE® CLL-1 clinical trial evaluating
epcoritamab (Abstract #883), a T-cell engaging bispecific antibody
administered subcutaneously, demonstrated an overall response rate
(ORR) of 61 percent and a complete response (CR) rate of 39 percent
in difficult-to-treat adult patients with relapsed or refractory
(R/R) chronic lymphocytic leukemia (CLL) treated with epcoritamab
monotherapy. These results, from the monotherapy expansion (EXP)
cohort (n=23) of the trial, along with the first safety data from
the optimization (OPT) cohort, were presented at the 66th Annual
Meeting and Exposition of the American Society of Hematology (ASH),
during the ASH Annual Meeting Press Program. The data will be
presented during an oral session on December 9, 2024.
In the EXP cohort, the median time to response was two (2.0)
months and the median time to CR was 5.6 months. Among all patients
in the cohort, median progression-free survival (PFS) was 12.8
months and median overall survival (OS) was not reached (median
follow-up was 22.8 months). An estimated 65 percent of patients
were alive at 15 months. Among 12 responders evaluable for minimal
residual disease (MRD) by next-generation sequencing in peripheral
blood, nine patients (75 percent) had undetectable MRD.
The most frequent non-hematologic treatment-emergent adverse
events (TEAEs) in the EXP cohort were cytokine release syndrome
(CRS; 96 percent), diarrhea (48 percent), peripheral edema (48
percent), fatigue (43 percent), and injection-site reaction (43
percent). Cytopenias were common (anemia, 65 percent;
thrombocytopenia, 65 percent; neutropenia, 48 percent); however,
most patients had baseline anemia and thrombocytopenia, suggesting
that these events were largely disease-related. Three cases of
immune effector cell-associated neurotoxicity syndrome (ICANS) were
reported (one Grade 1; two Grade 2), and there was one clinical
tumor lysis syndrome (CTLS) case (Grade 2). These cases did not
lead to treatment discontinuation. Four fatal TEAEs occurred - two
cases of pneumonia, one case of sepsis and one case of squamous
cell carcinoma of the skin.
The EXP cohort followed a 2-step step-up dose regimen, and CRS
was manageable and primarily low grade (9 percent Grade 1, 70
percent Grade 2, 17 percent Grade 3). In the first data from the
separate OPT cohort, which followed a 3-step step-up dose regimen,
CRS severity was substantially reduced with only low-grade events
(71 percent Grade 1, 12 percent Grade 2). In both cohorts, CRS
events primarily occurred following the first full dose, and none
led to treatment discontinuation. No ICANS or CTLS cases were
reported in the OPT cohort.
“These EPCORE CLL-1 data are encouraging, especially as the
majority of patients were heavily pre-treated with at least four
lines of therapy,” said Alexey Danilov, MD, PhD, Marianne and
Gerhard Pinkus, Professor and Director of Early Clinical
Therapeutics and Associate Director of the Toni Stephenson Lymphoma
Center, Department of Hematology and Hematopoietic Cell
Transplantation, City of Hope. “Despite progress in treating
chronic lymphocytic leukemia, there remains a tremendous need for
additional therapeutic options for high-risk patients whose disease
has progressed following standard chemoimmunotherapy and targeted
therapies.”
Additional data from the EXP cohort showed high response rates
in patients with high-risk factors treated with epcoritamab,
including TP53 aberrations, IGHV-unmutated disease and
double-exposed disease – prognostic markers that are associated
with disease progression and decreased survival.i,ii,iii In
patients with TP53 aberrations (n=15), the ORR was 67 percent with
a CR of 33 percent. Among patients with IGHV-unmutated disease
(n=16), the ORR was 63 percent, and the CR was 44 percent. In
double-refractory patients, the ORR was 53 percent, and the CR was
37 percent.
All patients in the trial had prior chemoimmunotherapy, and most
patients had previously received targeted therapies such as BTK and
BCL2 inhibitors (double-exposed) and had high-risk disease
characteristics.
“Chronic lymphocytic leukemia is incurable, and patients often
need a variety of treatments throughout their lifetime, especially
if their disease has high-risk prognostic factors, has relapsed or
has become refractory to the current standard-of-care, including
targeted therapies,” said Dr. Judith Klimovsky, Executive Vice
President & Chief Development Officer, Genmab. “These early
data show the potential therapeutic applicability of epcoritamab in
relapsed or refractory chronic lymphocytic leukemia, and further
reinforce the potential of epcoritamab as a core therapy for the
treatment of B-cell malignancies.”
Use of epcoritamab in CLL 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 CLL have not been established.
About Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is the most prevalent type of
leukemia, affecting over 200,000 people in the United States
alone.iv Chronic lymphocytic leukemia can be classified as either
slow growing (indolent) or fast growing (aggressive).v CLL is
incurable, and many patients will likely relapse and progress on
frontline therapies.vi Most patients will experience consecutive
episodes of disease progression and will require several lines of
treatment in their lifetime.vii,viii
About the EPCORE® CLL-1 Trial
EPCORE® CLL-1 is a Phase 1b/2, open-label, multi-center trial to
evaluate the safety and preliminary efficacy of epcoritamab as a
monotherapy and in combination with standard of care agents in
patients with difficult-to-treat relapsed/refractory (R/R) chronic
lymphocytic leukemia (CLL), R/R small lymphocytic lymphoma (SLL)
and Richter's Syndrome (RS). The trial consists of two parts: a
dose-escalation phase (Phase 1b) and an expansion phase (Phase 2).
Patients with RS are only included in the expansion phase. The
primary objective of Phase 1b is to determine the recommended Phase
2 dose and the maximum tolerated dose as well as establish the
safety profile of epcoritamab monotherapy and epcoritamab plus
venetoclax in participants with R/R CLL. The purpose of Phase 2 is
to assess and evaluate the preliminary efficacy, safety and
tolerability profiles of epcoritamab monotherapy and epcoritamab
plus venetoclax for patients with R/R CLL and SLL. Additionally,
epcoritamab monotherapy and combination therapy will be evaluated
in patients with RS to assess their efficacy, safety and
tolerability profiles. More information on this trial can be found
at https://www.clinicaltrials.gov/ (NCT: 04623541).
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.ix
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.
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. Both companies
will pursue additional international regulatory approvals for the
investigational R/R FL indication and additional approvals for the
R/R DLBCL indication.
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 five ongoing Phase
3, open-label, randomized trials including a trial evaluating
epcoritamab as a monotherapy in patients with R/R DLBCL compared to
investigator's choice chemotherapy (NCT04628494), a trial
evaluating epcoritamab in combination with R-CHOP in adult patients
with newly diagnosed DLBCL (NCT05578976), a trial evaluating
epcoritamab in combination with rituximab and lenalidomide (R2) in
patients with R/R FL (NCT05409066), a trial evaluating epcoritamab
in combination with rituximab and lenalidomide (R2) compared to
chemoimmunotherapy in patients with previously untreated FL
(NCT06191744), and a trial evaluating epcoritamab in combination
with lenalidomide compared to chemotherapy infusion in patients
with R/R DLBCL (NCT06508658). The safety and efficacy of
epcoritamab has not been established for these investigational
uses. Please visit www.clinicaltrials.gov for more information.
EPKINLY® (epcoritamab-bysp) U.S. INDICATIONS & IMPORTANT
SAFETY INFORMATION
What is EPKINLY?
EPKINLY is a prescription medicine used to treat adults with
certain types of diffuse large B-cell lymphoma (DLBCL), high-grade
B-cell lymphoma, or follicular lymphoma (FL) that has come back or
that did not respond to previous treatment after receiving 2 or
more treatments. EPKINLY is approved based on patient response
data. Studies are ongoing to confirm the clinical benefit of
EPKINLY. It is not known if EPKINLY is safe and effective in
children.
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 will receive EPKINLY on a step-up
dosing schedule (when you receive 2 or 3 smaller step-up doses of
EPKINLY before your first full dose during your first cycle of
treatment), and you may also receive other medicines before and for
3 days after receiving EPKINLY. 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.
People with DLBCL or high-grade B-cell lymphoma should be
hospitalized for 24 hours after receiving their first full dose of
EPKINLY on day 15 of cycle 1 due to the risk of CRS and neurologic
problems.
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. If you have any symptoms that impair consciousness,
do not drive or use heavy machinery or do other dangerous
activities until your symptoms go away.
EPKINLY can cause other serious side effects,
including:
- Infections that may lead to death. Your healthcare
provider will check you for signs and symptoms of infection before
and during treatment and treat you as needed if you develop an
infection. You should receive medicines from your healthcare
provider before you start treatment to help prevent infection. 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, which 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.
In DLBCL or high-grade B-cell lymphoma, 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. The most common severe abnormal
laboratory test results include decreased white blood cells,
decreased red blood cells, and decreased platelets.
In follicular lymphoma the most common side effects of
EPKINLY include injection site reactions, CRS, COVID-19,
tiredness, upper respiratory tract infections, muscle and bone
pain, rash, diarrhea, fever, cough, and headache. The most
common severe abnormal laboratory test results include
decreased white blood cells and decreased red blood cells.
These are not all of 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 Full Prescribing Information and Medication Guide,
including Important Warnings.
Globally, prescribing information varies; refer to the
individual country product label for complete 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.
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 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 Campo, et al. TP53 Aberrations in Chronic Lymphocytic
Leukemia: An Overview of the Clinical Implications of Improved
Diagnostics. Haematologica. 2018 Nov 15;103(12):1956–1968.
https://haematologica.org/article/view/8691. ii Galieni, et al.
Unmutated IGHV at Diagnosis in Patients With Early Stage CLL
Independently Predicts for Shorter Follow-Up Time to First
Treatment (TTFT). Leukemia Research. 2024.
https://doi.org/10.1016/j.leukres.2024.107541. iii Zuber, et al.
Efficacy and Effectiveness Outcomes of Treatments for
Double-Exposed Chronic Lymphocytic Leukemia and Small Lymphocytic
Lymphoma Patients: A Systematic Literature Review. Cancer Medicine.
2024. https://doi.org/10.1002/cam4.70258. iv Fedele, et al. Chronic
Lymphocytic Leukemia: Time to Care for the Survivors. Journal of
Clinical Oncology. 2024.
https://ascopubs.org/doi/10.1200/JCO.23.02738. v Penn Medicine.
Chronic Lymphocytic Leukemia (CLL). Accessed November 2024.
https://www.pennmedicine.org/cancer/types-of-cancer/leukemia/types-of-leukemia/chronic-lymphocytic-leukemia.
vi Odetola, et al. Relapsed/Refractory Chronic Lymphocytic Leukemia
(CLL). Curr Hematol Malig Rep. 2023 Jun 6:1–14. doi:
10.1007/s11899-023-00700-z vii Moreno, Carol. Standard Treatment
Approaches for Relapsed/Refractory Chronic Lymphocytic Leukemia
After Frontline Chemoimmunotherapy. Hematology Am Soc Hematol Educ
Program. 2020 Dec 4;2020(1):33-40. doi:
10.1182/hematology.2020000086. viii Leukemia & Lymphoma
Society. Relapsed and Refractory CLL. Accessed November 2024.
https://www.lls.org/leukemia/chronic-lymphocytic-leukemia/treatment/relapsed-and-refractory.
ix Engelberts PJ, 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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