Author: Moro, Ana Maria ; Cunha-Junior, Geraldo Felício ; Hoffman, Eric W ; Ismael, Gustavo ; Yeda, Fernanda P ; Alves, Venancio A ; Smaletz, Oren ; de Morais, Ana Luiza Gomes ; Del Pilar Estevez-Diz, Maria ; Majumder, Indrani ; Nascimento, Ivana L O ; Dos Santos, Mariana Lopes ; Azevedo, Sergio J

ObjectiveTo investigate the efficacy and safety of hu3S193, a humanized anti-Lewis-Y monoclonal antibody, as a consolidation strategy in patients with platinum-sensitive recurrent epithelial ovarian cancer who achieved a second complete response after salvage platinum-doublet chemotherapy.MethodsThis single-arm phase II study accrued patients with recurrent epithelial ovarian cancer with Lewis-Y expression by immunohistochemistry who had achieved a second complete response after five to eight cycles of platinum-based chemotherapy. Patients received intravenous infusions of hu3S193, 30 mg/m2every 2 weeks starting no more than 8 weeks after the last dose of chemotherapy and continuing for 12 doses, until disease progression, or unacceptable toxicity. The primary endpoint was progression-free survival of the second remission. Secondary objectives were safety and pharmacokinetics.ResultsTwenty-nine patients were enrolled. Most had a papillary/serous histology tumor (94%), stage III disease at diagnosis (75%), and five (17%) underwent secondary cytoreduction before salvage chemotherapy. Two patients were not eligible for efficacy but were considered for toxicity analysis. Eighteen patients (62%) completed the full consolidation treatment while nine patients progressed on treatment. At the time of analysis, 23 patients (85%) of the eligible population had progressed and seven of these patients (26%) had died. Median progression-free survival of the second remission was 12.1 months (95% CI: 10.6–13.9), with a 1-year progression-free survival of the second remission rate of 50.1%. The trial was terminated early since it was unlikely that the primary objective would be achieved. The most commonly reported treatment-related adverse events were nausea (55%) and vomiting (51%).ConclusionsHu3S193 did not show sufficient clinical activity as consolidation therapy in patients with recurrent epithelial ovarian cancer who achieved a second complete response after platinum-based chemotherapy.Trial registrationNCT01137071.

01 Jan 2021·ClinicsQ4 · MEDICINE

Phase II trial of humanized anti-Lewis Y monoclonal antibody for advanced hormone receptor-positive breast cancer that progressed following endocrine therapy

Q4 · MEDICINE

ArticleOA

Author: Mano, Max ; Zorzetto, Marina M Costa ; Crocamo, Susanne ; Bonadio, Renata Colombo ; Serrano, Sergio V ; Freitas-Junior, Ruffo ; Smaletz, Oren ; Arai, Roberto Jun ; Hoff, Paulo M ; Testa, Laura

OBJECTIVESThe Lewis-Y antigen is expressed in 44%-90% of breast cancers (BCs). The expression of the antigen in carcinoma tissue differs from that in normal tissues. This study aimed to evaluate the clinical benefit of the humanized anti-Lewis Y monoclonal antibody, hu3S193, in advanced hormone receptor-positive and Lewis Y-positive BC after administration of endocrine therapy (ET).METHODSA single-arm phase II study was conducted in seven centers. Patients with advanced hormone receptor-positive BC who failed first-line ET were included. The inclusion criterion was the observation of tumoral expression of the Lewis Y antigen during immunohistochemistry. The treatment comprised hu3S193 antibody administration at weekly intravenous doses of 20 mg/m2 for 8-week cycles. The primary endpoint was the clinical benefit rate. ClinicalTrials.gov NCT01370239.RESULTSThe study stopped accrual following an unplanned interim analysis as the hu3S193 antibody lacked sufficient activity to justify continuation of the study. Twenty-two patients were enrolled, of whom 21 were included in the efficacy analysis. The clinical benefit rate was 19%, with four patients presenting with stable disease after 24 weeks. One patient with prolonged stable disease received medication for over 2 years. No partial or complete responses were observed. The median time to progression and overall survival was 5.4 and 37.5 months, respectively.CONCLUSIONSThe humanized anti-Lewis Y monoclonal antibody, hu3S193, exhibited insufficient activity in this cohort. However, the possibility of activity in a more strictly selected subgroup of patients with higher levels of Lewis Y tumoral expression cannot be overlooked.

01 Jul 2012·mAbsQ2 · MEDICINE

Correlation of ADCC activity with cytokine release induced by the stably expressed, glyco-engineered humanized Lewis Y-specific monoclonal antibody MB314

Q2 · MEDICINE

Article

Author: Andreas Nechansky ; Manfred Schuster ; Klaus Hajszan ; Iris Koller ; Nicole Halanek ; Ralf Kircheis ; Wolfgang Jost ; Gilbert Gorr

A major limitation to the application of therapeutic monoclonal antibodies (mAbs) is their reduced in vivo efficacy compared with the high efficacy measured in vitro. Effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) are dramatically reduced in vivo by the presence of high amounts of endogenous IgG in the serum. Recent studies have shown that modification of the glycosylation moieties attached to the Fc part of the mAb can enhance binding affinity to FcγRIIIα receptors on natural killer cells and thus may counteract the reduced in vivo efficacy. In the present study, a humanized IgG1/κ monoclonal antibody recognizing the tumor-associated carbohydrate antigen Lewis Y was stably produced in a moss expression system that allows glyco-engineering. The glyco-modified mAb (designated MB314) showed a highly homogeneous N-glycosylation pattern lacking core-fucose. A side-by-side comparison to its parental counterpart produced in conventional mammalian cell-culture (MB311, formerly known as IGN311) by fluorescence-activated cell sorting analysis confirmed that the target specificity of MB314 is similar to that of MB311. In contrast, ADCC effector function of MB314 was increased up to 40-fold whereas complement dependent cytotoxicity activity was decreased 5-fold. Notably, a release of immunostimulatory cytokines, including interferon γ, monocyte chemotactic protein-1 (MCP-1), interleukin-6 and tumor necrosis factor (TNF) was particularly induced with the glyco-modified antibody. TNF release was associated with CD14 (+) cells, indicating activation of monocytes.

100 Deals associated with IGN-311

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 1	-	Celltrion, Inc.	-
Neoplasms	Phase 1	DE	-	-
Neoplasms	Phase 1	-	PDL BioPharma, Inc.	-
Neoplasms	Phase 1	-	Celltrion, Inc.	-
Neoplasms	Phase 1	DE	-	-
Neoplasms	Discovery	-	PDL BioPharma, Inc.	-

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