Delving into the Latest Updates on Epratuzumab Y-90 with Synapse

Overview

Basic Info

Drug Type

Radiolabeled antibody, Therapeutic radiopharmaceuticals

Synonyms

90Y-Epratuzumab, Anti-CD22 monoclonal antibody LL2-Y-90, Monoclonal antibody LL2-Y-90

+ [9]

Target

CD22

Mechanism

CD22 inhibitors(CD22 inhibitors)

Therapeutic Areas

NeoplasmsImmune System DiseasesHemic and Lymphatic Diseases+ [1]

Active Indication-

Inactive Indication

Aggressive B-Cell Non-Hodgkin LymphomaB-Cell LymphomaCD22 Positive B-cell Acute Lymphoblastic Leukemia+ [5]

Originator Organization

Immunomedics, Inc.

Active Organization-

Inactive Organization

Gilead Sciences, Inc.

Nantes University Hospital

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

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Gene Sequence

Sequence Code 146718

Sequence Code 9620786

A Phase I/II clinical trial using a fractionated dosing regimen of 90Y-epratuzumab (anti-CD22) has showed encouraging responses in follicular and aggressive NHL with an ability to administer safely 2 injections of 20 mCi/m2 spaced 1 week apart. The investigators propose to combine this active 90Y-epratuzumab treatment with a regimen of veltuzumab that was also found active in Phase I/II trials.
The goal of this study is to determine the safety and efficacy of 90Y-epratuzumab when used in combination with veltuzumab. The primary objective is to determine the response rate of this combination treatment. Secondary objectives are to assess safety, pharmacokinetics and targeting of 90Y-epratuzumab . Veltuzumab blood levels and anti-antibody responses will also be monitored at various times.

Start Date01 Oct 2010

Sponsor / Collaborator

Weill Medical College of Cornell University

[+1]

NCT01101581 / WithdrawnPhase 1/2

Phase I/II Study of Veltuzumab Combined With 90Y-Epratuzumab Tetraxetan in Patients With Relapsed/Refractory, Aggressive Non- Hodgkin's Lymphoma

The goal of this study is to evaluate a new approach to immunotherapy in NHL by combining two antibodies, veltuzumab and epratuzumab. For treatment, epratuzumab has also been attached to a radioactive isotope called 90yttrium (90Y-epratuzumab). Veltuzumab and 90Y-epratuzumab attack different areas on lymphoma cells. Because of this, treatment with the combination may provide more effective treatment in NHL than either veltuzumab or 90Y-epratuzumab given alone.

Start Date01 May 2010

Sponsor / Collaborator

Gilead Sciences, Inc.

100 Clinical Results associated with Epratuzumab Y-90

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100 Translational Medicine associated with Epratuzumab Y-90

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100 Patents (Medical) associated with Epratuzumab Y-90

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20

Literatures (Medical) associated with Epratuzumab Y-90

01 Jan 2017·The Lancet HaematologyQ1 · MEDICINE

Consolidation anti-CD22 fractionated radioimmunotherapy with 90 Y-epratuzumab tetraxetan following R-CHOP in elderly patients with diffuse large B-cell lymphoma: a prospective, single group, phase 2 trial

Q1 · MEDICINE

Article

Author: Sadot, Sophie ; Bodet-Milin, Caroline ; Gressin, Remy ; Wegener, William A ; Deau, Bénédicte ; Goldenberg, David M ; Vuillez, Jean-Philippe ; Pallardy, Amandine ; Jardel, Henry ; Berthou, Christian ; Soubeyran, Pierre ; Bouabdallah, Krimo ; Moreau, Anne ; Gouilleux-Gruart, Valérie ; Barbet, Jacques ; Kraeber-Bodere, Françoise ; Le Gouill, Steven ; Tournilhac, Olivier ; Moles, Marie-Pierre ; Cazeau, Anne-Laure ; Campion, Loïc ; Gyan, Emmanuel ; Maisonneuve, Hervé ; Morineau, Nadine ; Lamy, Thierry ; Salaun, Pierre-Yves ; Soubeyran, Isabelle ; Moreau, Philippe ; Daguindau, Etienne ; Garin, Etienne

BACKGROUNDRadioimmunotherapy represents a potential option as consolidation after chemoimmunotherapy in patients with diffuse large B-cell lymphoma who are not candidates for transplantation. We aimed to assess activity and toxicity of fractionated radioimmunotherapy using anti-CD22 ⁹⁰Y-epratuzumab tetraxetan as consolidation after front-line induction chemoimmunotherapy in untreated elderly patients with diffuse large B-cell lymphoma.METHODSWe did a prospective, single-group, phase 2 trial at 28 hospitals in France, with patients recruited from 17 hospitals. Eligible patients were aged 60-80 years with bulky stage 2-3 or stage 3-4 CD20-positive diffuse large B-cell lymphoma, previously untreated, and not eligible for transplantation. Patients received six cycles of R-CHOP (rituximab [375 mg/m²], cyclophosphamide [750 mg/m²], doxorubicin [50 mg/m²], and vincristine [1·4 mg/m², up to 2 mg] all on day 1, and prednisone [40 mg/m²] daily for 5 days), administered every 14 days. 6-8 weeks after R-CHOP, responders received two doses of 15 mCi/m² (555 MBq/m²) ⁹⁰Y-epratuzumab tetraxetan administered 1 week apart. The primary endpoint was 2 year event-free survival in all registered eligible patients who received at least 1 day of study treatment; the safety analysis was done in the same population. This trial is registered with ClinicalTrials.gov, number NCT00906841.FINDINGSBetween Oct 22, 2008, and Dec 16, 2010, we recruited 75 patients, of whom four (5%) were excluded after central pathology review; hence, 71 (95%) patients were included in the analysis. All patients started induction treatment; 57 (80%) received radioimmunotherapy. With a median follow-up of 37 months (IQR 30-44), the estimated 2 year event-free survival was 75% (95% CI 63-84). Radioimmunotherapy toxicity consisted of grade 3-4 thrombocytopenia in 48 (84%) of 57 patients and neutropenia in 45 (79%) of 57 patients. One patient developed myelodysplastic syndrome 28 months after receiving radioimmunotherapy and one patient developed acute myeloid leukaemia 5 months after receiving radioimmunotherapy.INTERPRETATIONFractionated radioimmunotherapy with ⁹⁰Y-epratuzumab tetraxetan might be appropriate for response consolidation after induction chemotherapy in older patients with advanced diffuse large B-cell lymphoma, but further comparative studies are needed.FUNDINGImmunomedics, Amgen, Canceropôle Grand Ouest, the GOELAMS/LYSA group and the French National Agency for Research (Investissements d'Avenir).

01 Mar 2015·The Lancet HaematologyQ1 · MEDICINE

90 Y-labelled anti-CD22 epratuzumab tetraxetan in adults with refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia: a phase 1 dose-escalation study

Q1 · MEDICINE

Article

Author: Alain Faivre-Chauvet ; Jacques Delaunay ; Claire Le Houerou ; Pierre Peterlin ; Simona Lapusan ; Françoise Huguet ; Mathilde Hunault ; Antoine Marcais ; William A Wegener ; Marion Eveillard ; Françoise Kraeber-Bodéré ; Marie C Bene ; Thierry Guillaume ; Michel Cherel ; Patrice Chevallier ; Norbert Ifrah ; Nelly Robillard ; Xavier Thomas ; Caroline Bodet-Milin ; Franck Nicolini ; Ludovic Ferrer ; Jacques Barbet ; Martine Escoffre-Barbe ; Joelle Gaschet ; David M Goldenberg ; Thomas Eugene ; Françoise Isnard

BACKGROUNDPrognosis of patients with relapsed or refractory acute lymphoblastic leukaemia is poor and new treatments are needed. We aimed to assess the feasibility, tolerability, dosimetry, and efficacy of yttrium-90-labelled anti-CD22 epratuzumab tetraxetan ((90)Y-DOTA-epratuzumab) radioimmunotherapy in refractory or relapsed CD22-positive B-cell acute lymphoblastic leukaemia in a standard 3 + 3 phase 1 study.METHODSAdults (≥18 years) with relapsed or refractory B-cell acute lymphoblastic leukaemia (with CD22 expression on at least 70% of blast cells) were enrolled at six centres in France. Patients received one cycle of (90)Y-DOTA-epratuzumab on days 1 and 8 (give or take 2 days) successively at one of four dose levels: 2·5 mCi/m(2) (92·5 MBq/m(2); level 1), 5·0 mCi/m(2) (185 MBq/m(2); level 2), 7·5 mCi/m(2) (277·5 MBq/m(2); level 3), and 10·0 mCi/m(2) (370 MBq/m(2); level 4). The primary objective was to identify the maximum tolerated dose of (90)Y-DOTA-epratuzumab. We assessed safety during infusions and regularly after radioimmunotherapy over a 6-month period. Analyses included only patients who received radioimmunotherapy. The trial is closed to inclusion and is registered at ClinicalTrials.gov, NCT01354457.FINDINGSBetween Aug 25, 2011, and June 11, 2014, 17 patients (median age 62 years; range 27-77) were treated (five at level 1, three at level 2, three at level 3, and six at level 4). Radioimmunotherapy infusion was overall well tolerated. One dose-limiting toxic effect (aplasia lasting 8 weeks) occurred at level 4, but the maximum tolerated dose was not reached. The most common grade 3-4 adverse events were pancytopenia (one patient at level 2, one at level 3, and six at level 4) and infections (three at level 1, one at level 2, and five at level 4).INTERPRETATION(90)Y-DOTA-epratuzumab radioimmunotherapy is well tolerated. We recommend the dose of 2 × 10·0 mCi/m(2) 1 week apart per cycle for phase 2 studies.FUNDINGImmunomedics and Direction de la Recherche Clinique of Nantes.

01 Nov 2014·HaematologicaQ1 · MEDICINE

Anti-CD22 90Y-epratuzumab tetraxetan combined with anti-CD20 veltuzumab: a phase I study in patients with relapsed/refractory, aggressive non-Hodgkin lymphoma

Q1 · MEDICINE

Article

Author: Tomblyn, Michael B ; Sharkey, Robert M ; Wegener, William A ; Kio, Ebenezer A ; Goldenberg, David M ; Misleh, Jamal G ; Witzig, Thomas E

A lingering criticism of radioimmunotherapy in non-Hodgkin lymphoma is the use of cold anti-CD20 antibody along with the radiolabeled anti-CD20 antibody. We instead combined radioimmunotherapy with immunotherapy targeting different B-cell antigens. We evaluated the anti-CD22 (90)Y-epratuzumab tetraxetan with the anti-CD20 veltuzumab in patients with aggressive lymphoma in whom at least one prior standard treatment had failed, but who had not undergone stem cell transplantation. Eighteen patients (median age 73 years, median of 3 prior treatments) received 200 mg/m(2) veltuzumab once-weekly for 4 weeks, with (90)Y-epratuzumab tetraxetan at planned doses in weeks 3 and 4, and (111)In-epratuzumab tetraxetan in week 2 for imaging and dosimetry. Veltuzumab effectively lowered levels of B cells in the blood prior to the radioimmunotherapy doses. No significant immunogenicity or change in pharmacokinetics of either agent occurred in combination. (111)In imaging showed tumor targeting with acceptable radiation dosimetry to normal organs. For (90)Y-epratuzumab tetraxetan, transient myelosuppression was dose-limiting with 6 mCi/m(2) (222 MBq/m(2)) × 2 being the maximal tolerated dose. Of 17 assessable patients, nine (53%) had objective responses according to the 2007 revised treatment response criteria, including three (18%) complete responses (2 relapsing after 11 and 13 months, 1 continuing to be clinically disease-free at 19 months), and six (35%) partial responses (1 relapsing after 14 months, 5 at 3 - 7 months). Responses occurred in patients with different lymphoma histologies, treated at different (90)Y dose levels, and with a predicted risk of poor outcome, most importantly including five of the six patients treated with the maximal tolerated dose (2 of whom achieved durable complete responses). In conclusion, the combination of (90)Y-epratuzumab tetraxetan and veltuzumab was well-tolerated with encouraging therapeutic activity in this difficult-to-treat population.

100 Deals associated with Epratuzumab Y-90

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Pre B-cell acute lymphoblastic leukemia	NDA/BLA	FR	Nantes University Hospital	26 Jul 2016
Lymphoid Leukemia	NDA/BLA	-	Nantes University Hospital	16 Oct 2015
B-Cell Lymphoma	Phase 3	FR	Gilead Sciences, Inc.	01 Aug 2002
CD22 Positive B-cell Acute Lymphoblastic Leukemia	Phase 2	FR	Nantes University Hospital	26 Jul 2016
Lymphoid Leukemia	Phase 2	-	Gilead Sciences, Inc.	16 Oct 2015
Refractory B Acute Lymphoblastic Leukemia	Phase 2	FR	Nantes University Hospital	01 Nov 2010
Follicular Lymphoma	Phase 2	US	Gilead Sciences, Inc.	01 Oct 2010
Aggressive B-Cell Non-Hodgkin Lymphoma	Phase 2	US	Gilead Sciences, Inc.	01 May 2010
Diffuse Large B-Cell Lymphoma	Phase 2	US	Gilead Sciences, Inc.	01 May 2010
B-Cell Lymphoma	Phase 2	DE	Gilead Sciences, Inc.	01 Aug 2002

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00906841 (Pubmed \| Lancet Haematol) Manual	Phase 2	Diffuse Large B-Cell Lymphoma	71	R-CHOP+90 Y-epratuzumab tetraxetan	(lhjkpdjveq) = rbrffwbgvd gaifupxxfv (lhximoulyr, 63 - 84)	Positive	01 Jan 2017
NCT01354457 (Pubmed \| Lancet Haematol) Manual	Phase 1	CD22 Positive B-cell Acute Lymphoblastic Leukemia CD22 Positive	17	Y-DOTA-epratuzumab	(mcleldzyfd) = tiwsbagxso suxfzhawhm (xwausvkyhk ) View more	Positive	01 Mar 2015