Delving into the Latest Updates on Anti-Lewis Y monoclonal antibody(Ludwig Institute for Cancer Research) with Synapse

The humanized monoclonal antibody against Lewis Y antigen (Hu3S193) has been demonstrated to be safe in previous studies and has also been indicated as potential intervention in breast cancer. The study of this new agent in advanced breast cancer may contribute to the development of new strategies for patients that progressed after hormonal treatment.

Start Date01 Nov 2013

Sponsor / Collaborator

Instituto do Cancer do Estado de Sao Paulo

[+2]

NCT01137071 / TerminatedPhase 2

A Phase II Trial of Hu3S193 Consolidation Therapy for Patients With Relapsing Platinum-sensitive Ovarian, Primary Peritoneal and Fallopian Tubes Adenocarcinoma, Who Achieved a Second Complete Response

RATIONALE: Monoclonal antibodies, such as Hu3S193, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase II trial is studying how well Hu3S193 works as a consolidation therapy for women with relapsing platinum-sensitive ovarian, primary peritoneal or fallopian tube cancer.

Start Date01 Apr 2011

Sponsor / Collaborator

Recepta Biopharma SA

NCT00617773 / CompletedPhase 2

A PHASE II TRIAL OF Hu3S193 THERAPY FOR PATIENTS WITH PLATINUM REFRACTORY OR PLATINUM RESISTANT EPITHELIAL OVARIAN, PRIMARY PERITONEAL AND FALLOPIAN TUBE CANCER

RATIONALE: Monoclonal antibodies, such as Hu3S193, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them.
PURPOSE: This phase II trial is studying how well Hu3S193 works in treating patients with ovarian epithelial cancer, fallopian tube cancer, or peritoneal cavity cancer.

Start Date01 May 2008

Sponsor / Collaborator

Recepta Biopharma SA

100 Clinical Results associated with Anti-Lewis Y monoclonal antibody(Ludwig Institute for Cancer Research)

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100 Translational Medicine associated with Anti-Lewis Y monoclonal antibody(Ludwig Institute for Cancer Research)

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100 Patents (Medical) associated with Anti-Lewis Y monoclonal antibody(Ludwig Institute for Cancer Research)

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Literatures (Medical) associated with Anti-Lewis Y monoclonal antibody(Ludwig Institute for Cancer Research)

01 Apr 2021·International Journal of Gynecologic CancerQ3 · MEDICINE

Phase II consolidation trial with anti-Lewis-Y monoclonal antibody (hu3S193) in platinum-sensitive ovarian cancer after a second remission

Q3 · MEDICINE

Article

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.

16 Jul 2018·Biochemical JournalQ3 · BIOLOGY

Global conformational changes in IgG-Fc upon mutation of the FcRn-binding site are not associated with altered antibody-dependent effector functions

Q3 · BIOLOGY

Article

Author: King, Dylan ; Liu, Zhanqi ; Burvenich, Ingrid J.G. ; Ramsland, Paul A. ; Gloria, Benjamin ; Farrugia, William ; Scott, Andrew M. ; Perani, Angelo ; Makris, Dahna ; Allan, Laura C.

Antibody engineering is important for many diagnostic and clinical applications of monoclonal antibodies. We recently reported a series of fragment crystallizable (Fc) mutations targeting the neonatal Fc receptor (FcRn) site on a Lewis Y (Ley) binding IgG1, hu3S193. The hu3S193 variants displayed shortened in vivo half-lives and may have potential for radioimaging or radiotherapy of Ley-positive tumors. Here, we report Fc crystal structures of wild-type hu3S193, seven FcRn-binding site variants, and a variant lacking C1q binding or complement-dependent cytotoxicity (CDC) activity. The Fc conformation of the FcRn-binding sites was similar for wild-type and all mutants of hu3S193 Fc, which suggests that FcRn interactions were directly affected by the amino acid substitutions. The C1q-binding site mutant Fc was nearly identical with the wild-type Fc. Surprisingly, several hu3S193 Fc variants showed large changes in global structure compared with wild-type Fc. All hu3S193 Fc mutants had similar antibody-dependent cellular cytotoxicity, despite some with conformations expected to diminish Fc gamma receptor binding. Several hu3S193 variants displayed altered CDC, but there was no correlation with the different Fc conformations. All versions of hu3S193, except the C1q-binding site mutant, bound C1q, suggesting that the altered CDC of some variants could result from different propensities to form IgG hexamers after engaging Ley on target cells. Overall, our findings support the concept that the antibody Fc is both flexible and mobile in solution. Structure-based design approaches should take into account the conformational plasticity of the Fc when engineering antibodies with optimal effector properties.

100 Deals associated with Anti-Lewis Y monoclonal antibody(Ludwig Institute for Cancer Research)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Platinum-Resistant Fallopian Tube Carcinoma	Phase 2	BR	Recepta Biopharma SA	01 May 2008
Primary peritoneal carcinoma	Phase 2	BR	Recepta Biopharma SA	01 May 2008
Breast Cancer	Phase 2	-	University of Sao Paulo	-
Breast Cancer	Phase 2	-	Ludwig Institute for Cancer Research Ltd.	-
Fallopian Tube Carcinoma	Phase 2	-	University of Sao Paulo	-
Fallopian Tube Carcinoma	Phase 2	-	Ludwig Institute for Cancer Research Ltd.	-
Ovarian Cancer	Phase 2	-	University of Sao Paulo	-
Ovarian Cancer	Phase 2	-	Ludwig Institute for Cancer Research Ltd.	-
Peritoneal Neoplasms	Phase 2	-	University of Sao Paulo	-
Peritoneal Neoplasms	Phase 2	-	Ludwig Institute for Cancer Research Ltd.	-

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Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00084799 (CTgov)	Phase 1	Small Cell Lung Cancer	10	monoclonal antibody hu3S193 (hu3S193 10 mg/m2)	hovlciujvh(hiruayqzyj) = uxzyaextgj insohrpswa (cvtpqivhdu, dfdljfmhvw - lvlzdzjfci) View more	-	08 Feb 2022
NCT00084799 (CTgov)	Phase 1	Small Cell Lung Cancer	10	monoclonal antibody hu3S193 (hu3S193 20 mg/m2)	hovlciujvh(hiruayqzyj) = kksslankvg insohrpswa (cvtpqivhdu, mzuylthzas - jaajlmvosj) View more	-	08 Feb 2022
NCT00072410 (CTgov)	Phase 1	Ovarian Epithelial Carcinoma	7	111In-hu3S193 (Cohort 1)	hiihilssyi(gupnrdkbdz) = otdahzjiwy oztxkevvic (phfklpizfm, vxxxdsdure - xctwqnntlv) View more	-	21 Dec 2021
NCT00072410 (CTgov)	Phase 1	Ovarian Epithelial Carcinoma	7	111In-hu3S193 (Cohort 2)	hiihilssyi(gupnrdkbdz) = lwnqfiehcj oztxkevvic (phfklpizfm, auoqejfrat - xhdsqlkqke) View more	-	21 Dec 2021
NCT01370239 (Pubmed \| Clinics (Sao Paulo)) Manual	Phase 2	Hormone receptor positive breast cancer Second line hormone receptor-positive	21	hu3s193	(uwqxjhbctw) = lemjoytaqk hjgxyxpoge (honfynkalk ) View more	Positive	11 Oct 2021
NCT00006099 (CTgov)	Phase 1	Ovarian Cancer	1	Monoclonal antibody hu3S193 (Intraperitoneal (IP) Infusion of 111In-hu3S193)	eyqfuqchps(dhofmqyill) = wcvnnhxkft pzvunsxkfl (zvzjnytluo, jptntqqonn - egcoiagcrd) View more	-	12 Aug 2021
NCT00006099 (CTgov)	Phase 1	Ovarian Cancer	1	Monoclonal antibody hu3S193 (Intravenous Infusion of 111In-hu3S193)	sfqgwfdiea(rstytthvru) = itebcwablj ifuaeearep (qjcfmdpust, ipotoipgtr - ahamxppbhk) View more	-	12 Aug 2021
NCT00006046 (CTgov)	Phase 1	Advanced Colorectal Adenocarcinoma	7	monoclonal antibody hu3S193 (Hu3S193 10 mg/m2)	kpdvtqyrqv(ajugmioaog) = vobwquovog pnmmxrmtkm (kygizfvabt, jjexseuaqo - nxpyygdsyv) View more	-	09 Aug 2021
NCT00006046 (CTgov)	Phase 1	Advanced Colorectal Adenocarcinoma	7	monoclonal antibody hu3S193 (Hu3S193 25 mg/m2)	kpdvtqyrqv(ajugmioaog) = bbzbopwanq pnmmxrmtkm (kygizfvabt, elqntfneqs - njhrmmleay) View more	-	09 Aug 2021
NCT01137071 (Pubmed \| Int J Gynecol Cancer)	Phase 2	Platinum-Sensitive Ovarian Carcinoma Consolidation	29	hu3S193	lmsngwnuzx(nslxaysjlv) = 55% ehfhhvgtnu (pwkzpvcrxa ) View more	Negative	04 Mar 2021
NCT01137071 (ASCO2017)	Phase 2	Platinum-Sensitive Ovarian Carcinoma Consolidation	29	hu3S193	(bysrnqxjou) = pcoxnnvqlr jawjhpfjaj (dygwpjpeut, 10.6 - 13.9)	Negative	30 May 2017
NCT00617773 (Pubmed \| Obstet Gynecol Surv)	Phase 2	Platinum-Resistant Primary Peritoneal Carcinoma	31	hu3S193	(ovbckntqog) = tfazpluroq etdltbycwy (cjlcicntpv, 9.77 - 46.71) View more	Negative	01 Aug 2015
NCT00617773 (CTgov)	Phase 2	Primary peritoneal carcinoma \| Platinum-Resistant Fallopian Tube Carcinoma	31	hu3S193	(rjwiploaza) = yjbjljpyoh wquvpjdtpf (exweemeiel, rifpcvgnrg - byyewsjrly) View more	-	26 Nov 2013
ASCO2011	Phase 2	Primary peritoneal carcinoma \| Fallopian Tube Carcinoma	31	hu3S193	(fngpxewabr) = efmxqpyynj amceafurwj (wcrqxkbcsd, 4 - 15)	-	20 May 2011