- Four oral presentations presented at ASH highlight data
evaluating investigational epcoritamab for the treatment of
relapsed/refractory (R/R) follicular lymphoma, previously untreated
follicular lymphoma, R/R diffuse large B-cell lymphoma and
Richter's syndrome
NORTH CHICAGO,
Ill., Dec. 11,
2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today
announced data from multiple clinical trials evaluating epcoritamab
(DuoBody®-CD3xCD20), an investigational subcutaneous
bispecific antibody, alone or in combination for the treatment of
patients with relapsed/refractory (R/R) follicular lymphoma (FL),
previously untreated FL, R/R diffuse large B-cell lymphoma (DLBCL),
as well as Richter's syndrome at the 64th American
Society of Hematology (ASH) Annual Meeting.
Notably, initial results of investigational epcoritamab in
patients with R/R FL and previously untreated FL are featured
during session 623 on Sunday, December
11 starting at 4:30 p.m. CST.
The results are part of the EPCORE™ NHL-2 study, a Phase
1b/2, open-label trial to assess the
safety and preliminary efficacy of epcoritamab in combination with
other agents in patients with B-cell non-Hodgkin's lymphoma,
including FL. Approximately 2.7 per 100,000 people in the U.S. are
newly diagnosed with FL every year and the median age of patients
at diagnoses with FL is 63.1,2,3 FL is typically a
slow-growing or indolent form of non-Hodgkin's lymphoma (NHL) that
arises from B-lymphocytes.4 Although FL is a
slow-growing lymphoma, it is considered incurable with conventional
therapy.5,6
"These data at this year's ASH meeting are promising as they
support continued investigation of epcoritamab for patients in need
of new treatment options for follicular lymphoma and other B-cell
lymphomas," said Mohamed Zaki, M.D.,
Ph.D., vice president and head, global oncology development,
AbbVie. "Along with Genmab, we look forward to continuing to build
on our promise of exploring a potential core therapy for patients
with B-cell malignancies in a variety of treatment settings."
Additional results from the EPCORE™ NHL-2 study as well as the
EPCORE™ CLL-1 study were presented for investigational epcoritamab
in R/R DLBCL and Richter's syndrome respectively. The EPCORE™ CLL-1
study is an open-label, multi-center, safety and efficacy trial of
epcoritamab in R/R chronic lymphocytic leukemia (CLL) and Richter's
syndrome. The trial consists of two parts, a dose escalation Phase
(Phase Ib) and an expansion Phase (Phase II).7
Abstract #609: Subcutaneous Epcoritamab with Rituximab
+ Lenalidomide in Patients with Relapsed or Refractory Follicular
Lymphoma: Phase 1/2 Trial Update
Oral Presentation: Sunday, December
11, 2022 at 5:00 p.m.
CST
In the R/R FL arm of the EPCORE™ NHL-2 trial, 95 percent (63/66)
of efficacy-evaluable patients treated with subcutaneous
epcoritamab in combination with rituximab and lenalidomide achieved
an overall response rate (ORR) and 80 percent (53/66) achieved
complete metabolic response (CMR). The majority of patients
achieved a response at first tumor response assessment and most
continued to respond through the latest assessment at the time of
data collection.
A manageable cytokine release syndrome (CRS) occurrence was
observed with only low-grade events, mainly following the first
full dose, all of which resolved. The most common
treatment-emergent adverse events (TEAEs) of any grade were
neutropenia (47%), CRS (43%), injection-site reactions (32%),
fatigue (31%), constipation (25%), COVID-19 (25%), pyrexia (25%)
and infusion-related reaction (21%).
Abstract #611: Subcutaneous Epcoritamab in Combination
with Rituximab + Lenalidomide for First-Line Treatment of
Follicular Lymphoma: Initial Results from Phase 1/2 Trial
Oral Presentation: Sunday, December
11, 2022 at 5:30 p.m.
CST
In the previously untreated FL patient arm of the EPCORE™ NHL-2
trial, 94 percent (34/36) of efficacy-evaluable patients who
received subcutaneous epcoritamab in combination with rituximab and
lenalidomide achieved an ORR, including 86 percent (31/36)
achieving CMR as their best overall response. In the trial, the
investigational combination therapy showed a manageable CRS
occurrence with only low-grade events, all of which
resolved.
The most common TEAEs of any grade were CRS (54%), neutropenia
(47%), pyrexia (44%), fatigue (37%), injection-site reaction (37%),
headache (34%), COVID-19 (33%), diarrhea (32%), constipation (29%),
rash (27%), increased alanine aminotransferase (ALT) (22%), and
vomiting (22%).
Abstract #443: Subcutaneous Epcoritamab + R-Dhax/C in
Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Eligible for Autologous Stem Cell Transplant: Updated Phase 1/2
Results
Oral Presentation: Sunday, December
11, 2022 at 10:30 a.m.
CST
Results from the EPCORE™ NHL-2 arm evaluating 27 patients with
R/R DLBCL who were eligible for autologous stem cell transplant,
showed an 85 percent (23/27) ORR and 67 percent (18/27) CMR
following treatment with the combination of subcutaneous
epcoritamab plus standard rituximab, dexamethasone, cytarabine, and
oxaliplatin or carboplatin (R-DHAX/C) salvage therapy.
The most common TEAEs of any grade were thrombocytopenia (69%),
anemia (51%), neutropenia (44%), CRS (41%), nausea (31%), fatigue
(28%), constipation (24%), diarrhea (24%), headache (24%), pyrexia
(24%) and increased aspartate aminotransferase (AST) (21%). All CRS
events were low-grade and resolved.
Abstract #348: Subcutaneous Epcoritamab in Patients
with Richter's Syndrome: Early Results from Phase 1b/2 Trial (EPCORE CLL-1)
Oral Presentation: Saturday, December
10, 2022 at 5:15 p.m.
CST
Preliminary results from the EPCORE™ CLL-1 trial showed that
treatment with subcutaneous epcoritamab monotherapy had promising
antitumor activity in 10 patients with Richter's syndrome, with a
60 percent ORR and a 50 percent CMR rate. Most responses were
observed by the first assessment at week six. In the trial,
patients experienced only low-grade CRS events, mostly associated
with the first full dose, all of which resolved.
The most common TEAEs of any grade were CRS (90%), anemia (50%),
neutropenia (50%), injection-site reaction (40%), thrombocytopenia
(40%), hypophosphatemia (30%), Hypokalemia (30%), hyperglycemia
(30%), COVID-19 (30%), diarrhea (30%), fatigue (30%), and nausea
(30%).
About Diffuse Large B-Cell Lymphoma (DLBCL)
DLBCL is a
fast-growing type of NHL that affects B-cell lymphocytes, a type of
white blood cell.8 It is the most common type of NHL
worldwide and accounts for approximately 30 percent of all NHL
cases.8 DLBCL can arise in lymph nodes, as well as in
organs outside of the lymphatic system.8 The disease
occurs more commonly in the elderly and is slightly more prevalent
in men.8
About Richter's Syndrome
Richter's syndrome, also
known as Richter's transformation, is defined as the transformation
of CLL into an aggressive lymphoma, most commonly
DLBCL.9,10 Richter's syndrome occurs in approximately 2
percent to 10 percent of CLL patients during the course of their
disease.9
About the EPCORE™ NHL-2 Trial
EPCORE™ NHL-2 is a Phase
1b/2, open-label, multinational,
interventional trial to evaluate the safety, tolerability,
pharmacokinetics, pharmacodynamics/biomarkers, immunogenicity, and
preliminary efficacy of epcoritamab in combination with other
standard-of-care agents in subjects with B-cell non-Hodgkin's
lymphoma. The trial consists of two parts: Part 1 (Dose Escalation)
and Part 2 (Dose Expansion).11
The primary objective of Part 1 is safety, and it includes Arm
1–5. Part 2 includes all 8 arms (Arm 1–8) and the primary goal of
all arms, except Arm 7, is preliminary efficacy. For Arm 7, the
primary goal is safety. Patients in Arm 1–5 can only participate in
either Part 1 or Part 2. Dose Limiting Toxicities will be assessed
in Part 1 and for a selected number of patients in Arm 8 during a
28-day period (safety-run Phase). The arms are conducted in
parallel.11
About Epcoritamab
Epcoritamab is an investigational
IgG1-bispecific antibody created using Genmab's proprietary DuoBody
technology. 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.12 CD20
is expressed on B-cells and a clinically validated therapeutic
target in many B-cell malignancies, including DLBCL, FL, mantle
cell lymphoma and CLL.13,14
AbbVie recently announced that the Biologics License Application
(BLA) for epcoritamab for the treatment of adult patients with R/R
large B-cell lymphoma after two or more lines of systemic therapy
was accepted for priority review by the U.S. Food and Drug
Administration. Additionally, the European Medicines Agency has
validated a Marketing Authorization Application for
epcoritamab for the treatment of adult patients with R/R DLBCL
after two or more lines of systemic therapy.
Epcoritamab is being co-developed by AbbVie and Genmab 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. The companies are committed to evaluating
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) and a Phase 3, open-label clinical trial evaluating
epcoritamab in combination in patients with R/R FL (NCT:
05409066).
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 and our Blood Cancer Press Kit
page.
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,
women's health and gastroenterology, in addition to products and
services across its Allergan Aesthetics portfolio. For more
information about AbbVie, please visit us at www.abbvie.com. Follow
@abbvie on Twitter, Facebook, Instagram, YouTube and LinkedIn.
AbbVie 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, among others, 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
indicated in the forward-looking statements. Such risks and
uncertainties include, but are not limited to, failure to realize
the expected benefits from AbbVie's acquisition of Allergan plc
("Allergan"), failure to promptly and effectively integrate
Allergan's businesses, competition from other products, challenges
to intellectual property, difficulties inherent in the research and
development process, adverse litigation or government action,
changes to laws and regulations applicable to our industry and the
impact of public health outbreaks, epidemics or pandemics, such as
COVID-19. 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 2021 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 to release publicly any revisions to forward-looking
statements as a result of subsequent events or developments, except
as required by law.
1 National Institutes of Health official website:
SEER Cancer Statistics. https://seer.cancer.gov/csr/1975_2017/.
Table 19.29. Accessed November
2022.
2 Cancer Stat Facts: Follicular Lymphoma.
https://seer.cancer.gov/statfacts/html/follicular.html. Accessed
November 2022
3 SEER Cancer Statistics.
https://seer.cancer.gov/csr/1975_2017/. Table 19.26. Accessed
November 2022.
4 Lymphoma Research Foundation official website.
https://lymphoma.org/aboutlymphoma/nhl/fl/. Accessed November 2022.
5 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.
6 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.
7 Safety & Efficacy Study of Epcoritamab in subjects
with R/R chronic lymphocytic leukemia and richter's syndrome.
ClinicalTrials.gov. (n.d.). Accessed November 2022, from
https://clinicaltrials.gov/ct2/show/NCT04623541
8 Sehn, Salles. Diffuse Large B-Cell Lymphoma. N Engl J
Med. 2021;384:842-858. DOI: 10.1056/NEJMra2027612.
9 Richter's syndrome. Leukaemia Foundation. (2022,
October 5). Accessed November 2022, from
https://www.leukaemia.org.au/blood-cancer-information/types-of-blood-cancer/leukaemia/chronic-lymphocytic-leukaemia/richters-syndrome/#:~:text=Richter's%20Syndrome%20(RS)%2C%20also,form%20of%20large%20cell%20lymphoma.
10 Parikh SA, Kay NE, Shanafelt TD. How we treat Richter
syndrome. Blood. 2014 Mar 13;123(11):1647-57. doi:
10.1182/blood-2013-11-516229. Epub 2014 Jan 13. PMID: 24421328;
PMCID: PMC3954047.
11 Safety and Efficacy Trial of Epcoritamab Combinations
in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL).
ClinicalTrials.gov. (n.d.). Accessed November 2022, from
https://clinicaltrials.gov/ct2/show/NCT04663347
12 Engelberts 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.
13 Rafiq, Butchar, Cheney, et al. "Comparative
Assessment of Clinically Utilized CD20-Directed Antibodies in
Chronic Lymphocytic Leukemia Cells Reveals Divergent NK Cell,
Monocyte, and Macrophage Properties." J. Immunol.
2013;190(6):2702-2711. DOI: 10.4049/jimmunol.1202588.
14 Singh, Gupta, Almasan. "Development of Novel
Anti-Cd20 Monoclonal Antibodies and Modulation in Cd20 Levels on
Cell Surface: Looking to Improve Immunotherapy Response." J Cancer
Sci Ther. 2015;7(11):347-358. DOI: 10.4172/1948-5956.1000373.
View original
content:https://www.prnewswire.com/news-releases/abbvie-presents-data-at-the-64th-american-society-of-hematology-ash-annual-meeting-evaluating-epcoritamab-duobody-cd3xcd20-across-b-cell-lymphomas-301699903.html
SOURCE AbbVie