- Based on the topline results of epcoritamab from the
EPCORE™ NHL-1 clinical trial, AbbVie and Genmab will engage global
regulatory authorities to discuss next steps
- Additional data from the clinical trial will be
presented at a future medical meeting
- Follicular lymphoma is a common form of non-Hodgkin's
lymphoma and currently has limited treatment options, particularly
in the relapsed/refractory setting
NORTH
CHICAGO, Ill., June 27,
2023 /PRNewswire/ -- AbbVie (NYSE: ABBV) and Genmab
(Nasdaq: GMAB) today announced topline results from the follicular
lymphoma (FL) cohort of the Phase 1/2 EPCORE™ NHL-1 clinical trial
evaluating epcoritamab (DuoBody®-CD3xCD20), an
investigational T-cell engaging bispecific antibody administered
subcutaneously. The study cohort includes 128 adult patients with
relapsed or refractory (R/R) FL who received at least two or more
lines of systemic therapy. 70.3 percent of patients were double
refractory to an anti-CD20 monoclonal antibody and an alkylating
agent. Epcoritamab is being co-developed by AbbVie and Genmab as
part of the companies' oncology collaboration.
"We are encouraged by these topline results, which further
support the clinical profile of epcoritamab as a potential
therapeutic option for patients with relapsed or refractory
follicular lymphoma," said Mariana Cota
Stirner, M.D., Ph.D., vice president, therapeutic area head
for hematology, AbbVie. "Together with our partner Genmab, these
results may bring us one step closer to our goal of advancing a
potential core therapy for patients with B-cell malignancies."
EPCORE™ NHL-1 is an open-label trial evaluating the safety and
preliminary efficacy of epcoritamab and consists of three parts: a
Phase 1 first-in-human, dose escalation part; a Phase 2a expansion
part; and a Phase 2a optimization part. The topline results from
this cohort showed an overall response rate (ORR) of 82 percent as
confirmed by an independent review committee (IRC), which exceeded
the protocol prespecified threshold for efficacy. The observed
median duration of response (DOR) was not reached, and longer
follow-up will be required. The median number of lines of prior
therapy in this cohort was three (range: two to four lines of
therapy).
No new safety signals were observed with epcoritamab in this
study at the time of this analysis. The most common
treatment-emergent adverse event was cytokine release syndrome
(CRS) with 66.4 percent (1.6 percent Grade 3 or higher). The
optimization part of the trial is continuing to evaluate
alternative step-up dosing regimens to help further mitigate the
risk of CRS, preliminary data are encouraging.
Full results from the study will be submitted for presentation
at a future medical meeting.
About the Phase 1/2 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 Phase 1
first-in-human, dose escalation part; a Phase 2a expansion part;
and a Phase 2a dose optimization part. The trial was designed to
evaluate subcutaneous epcoritamab in adult patients with relapsed,
progressive or refractory CD20+ mature B-cell non-Hodgkin's
lymphoma (NHL), including follicular lymphoma (FL). In the Phase 2a
expansion part, additional patients are being enrolled to further
explore the safety and efficacy of epcoritamab in three cohorts of
patients with different types of relapsed or refractory (R/R)
B-cell NHLs who have limited therapeutic options. The dose
optimization part evaluates the potential for alternative step-up
dosing regimens to help further minimize Grade 2 CRS and mitigate
Grade ≥3 cytokine release syndrome. The primary endpoint of the
expansion part was overall response rate as assessed by an
independent review committee. 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
evaluated as secondary efficacy endpoints.
About Follicular Lymphoma
Follicular lymphoma
(FL) is typically an indolent, or slow growing, form of NHL that
arises from B-cell lymphocytes.1 FL is the second most
common form of NHL overall, accounting for 20 to 30 percent of all
NHL cases, and representing 10 to 20 percent of all lymphomas in
the western world.2,3 Although FL is an indolent
lymphoma, it is considered incurable with conventional
therapy.4,5
About Epcoritamab
Epcoritamab is an
investigational 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.6
Epcoritamab-bysp (EPKINLY™) was recently approved in
the United States (U.S.) and is
indicated for the treatment of adult patients with R/R diffuse
large B-cell lymphoma (DLBCL), not otherwise specified (NOS),
including DLBCL arising from indolent lymphoma, and high-grade
B-cell lymphoma (HGBL) after two or more lines of systemic therapy.
This indication is approved under accelerated approval based on
response rate and durability of response. Continued approval for
this indication is contingent upon verification and description of
clinical benefit in a confirmatory trial(s). Please see U.S.
Important Safety Information below.
In October 2022, a Marketing
Authorization Application was submitted for epcoritamab for the
treatment of patients with R/R DLBCL after two or more lines of
systemic therapy, which was validated by the European Medicines
Agency. Additionally, in December
2022, a Japan new drug
application was submitted to the Ministry of Health, Labor and
Welfare of Japan for epcoritamab
for the treatment of patients with R/R large B-cell lymphoma (LBCL)
after two or more lines of systemic therapy. Epcoritamab is not
approved in the European Union and Japan.
The companies will share commercial responsibilities in
the United States and Japan,
with AbbVie responsible for further global
commercialization. AbbVie will continue to pursue regulatory
submissions for epcoritamab across international markets excluding
the United States and Japan throughout the year.
Genmab and AbbVie are continuing to evaluate the use of
epcoritamab as a monotherapy, and in combination, across lines of
therapy in a range of hematologic malignancies. This includes an
ongoing Phase 3, open-label, randomized trial evaluating
epcoritamab as a monotherapy in patients with R/R DLBCL (NCT:
04628494), an ongoing Phase 3, open-label, randomized trial
evaluating epcoritamab in combination in adult participants with
newly diagnosed DLBCL (NCT: 05578976), and a Phase 3, open-label
clinical trial evaluating epcoritamab in combination in patients
with R/R FL (NCT: 05409066). Epcoritamab is not approved to treat
newly diagnosed patients with DLBCL or FL. 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). CRS is common
during treatment with EPKINLY and can be serious or
life-threatening. Tell your healthcare provider or get medical help
right away if you develop symptoms of CRS, including fever of
100.4°F (38°C) or higher, dizziness or lightheadedness, trouble
breathing, chills, fast heartbeat, feeling anxious, headache,
confusion, shaking (tremors), or problems with balance and
movement, such as trouble walking.
Due to the risk of CRS, you will receive EPKINLY on a "step-up"
dosing schedule. The step-up dosing schedule is when you
receive smaller "step-up" doses of EPKINLY on day 1 and day 8 of
your first cycle of treatment (cycle 1). You will receive your
first full dose of EPKINLY on day 15 of cycle 1. If your dose of
EPKINLY is delayed for any reason, you may need to repeat the
step-up dosing schedule. Before each dose in cycle 1, you will
receive medicines to help reduce your risk of CRS. Your healthcare
provider will decide if you need to receive medicine to help reduce
your risk of CRS with future cycles.
- Neurologic problems. EPKINLY can cause serious
neurologic problems that can be life-threatening and lead to death.
Neurologic problems may happen days or weeks after you receive
EPKINLY. Your healthcare provider may refer you to a healthcare
provider who specializes in neurologic problems. Tell your
healthcare provider right away if you develop any symptoms of
neurologic problems, including trouble speaking or writing,
confusion and disorientation, drowsiness, tiredness or lack of
energy, muscle weakness, shaking (tremors), seizures, or memory
loss.
Due to the risk of CRS and neurologic problems, you
should be hospitalized for 24 hours after receiving your first full
dose of EPKINLY on day 15 of cycle 1. Your healthcare provider will
monitor you for symptoms of CRS and neurologic problems during
treatment with EPKINLY, as well as other side effects, and treat
you if needed. Your healthcare provider may temporarily stop or
completely stop your treatment with EPKINLY if you develop CRS,
neurologic problems, or any other side effects that are severe.
Do not drive or use heavy or potentially dangerous
machinery if you develop dizziness, confusion, tremors, drowsiness,
or any other symptoms that impair consciousness until your symptoms
go away. These may be symptoms of CRS or neurologic problems.
EPKINLY can also cause other serious side effects,
including:
- Infections. EPKINLY can cause serious infections
that may lead to death. Your healthcare provider will check you for
symptoms of infection before and during treatment. 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. 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 cell counts (neutropenia),
which can increase your risk for infection; low red blood
cell counts (anemia), which can cause tiredness and shortness
of breath; and low platelet counts (thrombocytopenia),
which can cause bruising or bleeding problems.
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 of your medical conditions, including if you:
- have an infection.
- are pregnant or plan to become pregnant. EPKINLY may harm your
unborn baby. Females who are able to become
pregnant: Your healthcare provider should do a pregnancy
test before you start treatment with EPKINLY. 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.
- are breastfeeding or plan to breastfeed. It is not known if
EPKINLY passes into your breast milk. Do not breastfeed during
treatment with EPKINLY and for 4 months after your last dose of
EPKINLY.
Tell your healthcare provider about all of the medicines you
take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
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 the Full Prescribing
Information and Medication Guide, including Important
Warnings.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of
care for multiple blood cancers while advancing a dynamic pipeline
of investigational therapies across a range of cancer types. Our
dedicated and experienced team joins forces with innovative
partners to accelerate the delivery of potential breakthrough
medicines. We are evaluating more than 20 investigational medicines
in over 300 clinical trials across some of the world's most
widespread and debilitating cancers. As we work to have a
remarkable impact on people's lives, we are committed to exploring
solutions to help patients obtain access to our cancer medicines.
For more information, please
visit http://www.abbvie.com/oncology.
About AbbVie
AbbVie's mission is to discover and deliver innovative medicines
that solve serious health issues today and address the medical
challenges of tomorrow. We strive to have a remarkable impact on
people's lives across several key therapeutic areas: immunology,
oncology, neuroscience, eye care, virology and gastroenterology, in
addition to products and services across our Allergan Aesthetics
portfolio. For more information about AbbVie, please visit us at
www.abbvie.com. Follow @abbvie on Twitter, Facebook, Instagram,
YouTube and LinkedIn.
Forward-Looking Statements
Some statements in this news release are, or may be
considered, forward-looking statements for purposes of the Private
Securities Litigation Reform Act of 1995. The words "believe,"
"expect," "anticipate," "project" and similar expressions and uses
of future or conditional verbs, generally identify forward-looking
statements. AbbVie cautions that these forward-looking statements
are subject to risks and uncertainties that may cause actual
results to differ materially from those expressed or implied in the
forward-looking statements. Such risks and uncertainties include,
but are not limited to, challenges to intellectual property,
competition from other products, difficulties inherent in the
research and development process, adverse litigation or government
action, and changes to laws and regulations applicable to our
industry. Additional information about the economic, competitive,
governmental, technological and other factors that may affect
AbbVie's operations is set forth in Item 1A, "Risk Factors," of
AbbVie's 2022 Annual Report on Form 10-K, which has been filed with
the Securities and Exchange Commission, as updated by its
subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no
obligation, and specifically declines, to release publicly any
revisions to forward-looking statements as a result of subsequent
events or developments, except as required by law.
1 What is Lymphoma. Lymphoma Research Foundation.
https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed June 22, 2023.
2 Ma S. Risk factors of follicular
lymphoma. Expert Opin Med Diagn. 2012;6:323–33.
DOI: 10.1517/17530059.2012.686996.
3 Luminari S, Bellei M, Biasoli I, et al.
Follicular lymphoma—treatment and prognostic factors. Rev
Bras Hematol Hemoter. 2012;34:54–9. DOI:
10.5581/1516-8484.20120015.
4 Link BK, Day BM, Zhou X, 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. DOI: 10.1111/bjh.15149.
5 Ren J, Asche CV, Shou Y, Galaznik A. 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.
DOI: 10.2217/cer-2018-0094.
6 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.
View original
content:https://www.prnewswire.com/news-releases/abbvie-and-genmab-announce-positive-topline-results-from-phase-12-epcore-nhl-1-trial-evaluating-epcoritamab-duobody-cd3xcd20-in-patients-with-relapsedrefractory-follicular-lymphoma-fl-301865086.html
SOURCE AbbVie