Immunomedics, Inc. IMMU, a
biopharmaceutical company primarily focused on the development of monoclonal
antibody-based products for the targeted treatment of cancer, autoimmune and
other serious diseases, today reported that small, repeated doses of
epratuzumab labeled with the radioisotope, yttrium-90 (^90Y), demonstrated
therapeutic activity in 2 clinical trials in patients with aggressive
non-Hodgkin lymphoma (NHL).
Epratuzumab is a humanized antibody that binds to the CD22 receptor on B
cells. In various clinical trials, epratuzumab was found to be active as an
unlabeled antibody in patients with NHL or lupus. Previous clinical studies
have also demonstrated that repeated administration of small doses of
^90Y-epratuzumab are tolerable in NHL patients and produced high rates of
durable responses.
Despite recent advances in the use of antibody for the management of NHL,
aggressive NHLs have proven to be more resistant to currently approved
antibody therapies unless they are combined with chemotherapy. Diffuse large
B-cell lymphoma (DLCBL) is the most common type of aggressive NHL, with
approximately 20,000 new patients diagnosed each year in the United States.
The standard-of-care for DLBCL is combining the anti-CD20 antibody, rituximab,
with the CHOP chemotherapy regimen, or R-CHOP. However, elderly patients who
fail R-CHOP have a poor outcome. Due to advanced age, chemo-resistant disease,
and/or concurrent co-morbid medical conditions, a significant percentage of
these patients are not eligible for high-dose salvage therapy or stem cell
transplant. Consequently, there is a need for alternative therapy for
high-risk patients with a lower chance of being cured with standard R-CHOP.
An innovative approach for NHL therapy that the Company and its outside
collaborators are developing is to combine antibody-directed radiation therapy
using ^90Y-epratuzumab with antibody therapy targeting a different antigen.
Since the two antibodies bind to two distinct antigens and do not cross-block
each other, this concept may offer more synergy than current NHL
radioimmunotherapy that employs unlabeled antibody targeting the same B-cell
antigen.
Updated results from a multicenter Phase II trial sponsored by the French LYSA
study group were reported in an oral presentation at this year's ASH Annual
Meeting by Pierre Soubeyran, MD, PhD, of the Bergonié Cancer Institut,
Bordeaux, France. The goal of this open-label study is to evaluate
^90Y-epratuzumab given in small doses as consolidation therapy after R-CHOP in
previously untreated elderly patients with advanced DLBCL. Primary end-point
of the study is 2-year event-free survival (EFS).
At the time of reporting, a total of 75 patients between the ages of 60 and 80
years had been enrolled to receive 6 cycles of R-CHOP therapy, with 61
patients eligible for 2 consolidation treatments of ^90Y-epratuzumab at 15
mCi/m^2.
Using the 1999 International Workshop for Response Criteria for NHL, the
overall response rate (ORR) after 6 cycles of R-CHOP therapy was 94.6%
(71/75), with 52 patients (69.3%) achieving a complete or unconfirmed complete
response (CR/CRu) and 19 patients (25.3%) reporting a partial response (PR).
At a median follow-up of 24 months (range from 1 - 46), 18 patients
experienced lymphoma progression and/or related death, yielding an estimated
2-year EFS of 73.3% (60.7 - 82.5%) and an estimated 2-year overall survival
(OS) of 83.2% (71.4 - 90.4%).
For the 61 patients who received the 2 consolidation ^90Y-epratuzumab
treatments, ORR was 91.8% (56/61), with 50 patients (81.9%) achieving a
CR/CRu. Eight of 16 patients (50.0%) who had less than a CR/CRu with R-CHOP
converted to CR/CRu after receiving radiolabeled epratuzumab. Among these 61
patients, 12 experienced progression and/or related death, yielding an
estimated 2-year EFS of 78.7% (65.1 - 87.4%) and an estimated 2-year OS of
90.1% (77.7 - 95.8%).
Separately, the Company is investigating a combination of ^90Y-epratuzumab and
its second-generation, humanized anti-CD20 antibody, veltuzumab, in patients
with relapsed aggressive NHL. Michael B Tomblyn, MD, of H. Lee Moffitt Cancer
Center, Tampa, FL, presented updated results at the same ASH medical
conference, with clinical research sites from Division of Hematology,
Department of Internal Medicine, Mayo Clinic, Rochester, MN; Helen F Graham
Cancer Center, Newark, DE; Weill Cornell Medical College, New York, NY; and
Indiana University Health Center for Cancer Care, Goshen, IN, participating in
this Phase I, open-label study.
Results from 18 patients with various types of aggressive NHL who had failed 1
or more prior standard therapies were reported at the conference. The ^90Y
dose was repeatedly de-escalated from 15 (N=3) to 12 (N=3), 9 (N=6), and
currently 6 (N=6) mCi/m^2 due to hematologic dose-limiting toxicities.
Otherwise, treatment was well-tolerated with no infusion reactions.
The overall objective response rate among 17 patients who have had treatment
response assessments was 53%, including one DLBCL patient (6%) with a CR
continuing 12 months later. The combination is active in all NHL subgroups and
across ^90Y dose levels. At the maximum tolerated dose of 6 mCi/m^2 x 2, 5 of
6 patients (83%) achieved PRs.
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