A Phase 2 Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma and Other Forms of Non-Hodgkin's Lymphoma

This is an open label, multicenter, adaptive Phase 2 clinical study. The study will consist of a screening period, a treatment period, an end of treatment visit, and a follow-up period.

开始日期2016-06-15

申办/合作机构

Debiopharm International SA

NCT01534715 / Completed临床1期

A Phase I, Multi-center, Open-label Study of IMGN529 Administered Intravenously in Adult Patients With Relapsed or Refractory Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

The purpose of this study is to test the safety and tolerability of IMGN529 in patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL).

开始日期2012-01-01

申办/合作机构

ImmunoGen, Inc.

100 项与 Naratuximab emtansine 相关的临床结果

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100 项与 Naratuximab emtansine 相关的转化医学

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100 项与 Naratuximab emtansine 相关的专利（医药）

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项与 Naratuximab emtansine 相关的文献（医药）

2018-10-01·Investigational new drugs3区 · 医学

Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study

3区 · 医学

Article

作者: Lia Palomba, M ; Flinn, Ian W ; Madan, Sumit ; Stathis, Anastasios ; Maddocks, Kami ; Weitman, Steven ; Freedman, Arnold ; Munteanu, Mihaela C ; Zucca, Emanuele

Summary:

Background CD37 is expressed on B-cell lymphoid malignancies, thus making it an attractive candidate for targeted therapy in non-Hodgkin lymphoma (NHL). IMGN529 is an antibody-drug conjugate comprising a CD37-binding antibody linked to the maytansinoid DM1, a potent anti-mitotic agent. Methods This first-in-human, phase 1 trial recruited adult patients with relapsed or refractory B-cell NHL. The primary objective was to determine the maximum tolerated dose (MTD) and recommended phase 2 dose. Secondary objectives were to evaluate safety, pharmacokinetics, and preliminary clinical activity. IMGN529 was administered intravenously once every 3 weeks, and dosed using a conventional 3 + 3 dose-escalation design. Results Forty-nine patients were treated at doses escalating from 0.1 to 1.8 mg/kg. Dose limiting toxicities occurred in eight patients and included peripheral neuropathy, febrile neutropenia, neutropenia, and thrombocytopenia. The most frequent treatment-emergent adverse events were fatigue (39%), neutropenia, pyrexia, and thrombocytopenia (each 37%). Adverse events led to treatment discontinuation in 10 patients (20%). Eight patients (16%) had treatment-related serious adverse events, the most common being grade 3 febrile neutropenia. The MTD (with growth factor support) was 1.4 mg/kg every 3 weeks. IMGN529 plasma exposure increased monotonically with dose and was consistent with target-mediated drug disposition. Five (13%) of 39 response-evaluable patients achieved an objective response (one complete response and four partial responses), four of which occurred in the subgroup of patients with diffuse large B-cell lymphoma. Conclusions The manageable safety profile of IMGN529 and preliminary evidence of activity, particularly in DLBCL patients, support the continued development of this novel CD37-targeting agent.

2017-09-01·Neoplasia (New York, N.Y.)2区 · 医学

The Antitumor Activity of IMGN529, a CD37-Targeting Antibody-Drug Conjugate, Is Potentiated by Rituximab in Non-Hodgkin Lymphoma Models

2区 · 医学

ArticleOA

作者: Romanelli, Angela ; Kelly, Meghan E ; Shah, Prerak ; Lanieri, Leanne ; Sloss, Callum M ; Ponte, Jose F ; Hicks, Stuart W ; Sikka, Surina ; Lai, Katharine C ; Lee, Jenny ; Gavrilescu, L Cristina ; Yi, Yong

Naratuximab emtansine (IMGN529) is an investigational antibody-drug conjugate consisting of a CD37-targeting antibody conjugated to the maytansine-derived microtuble disruptor, DM1. IMGN529 has shown promising preclinical and clinical activity in non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Due to the aggressive nature of the disease, DLBCL is often treated with combination therapies to maximize clinical outcomes; therefore, we investigated the potential of combining IMGN529 with both standard-of-care and emerging therapies against multiple oncology-relevant targets and pathways. The strongest enhancement in potency was seen with anti-CD20 antibodies, including rituximab. The combination of IMGN529 and rituximab was more potent than either agent alone, and this combinatorial benefit was associated with increased apoptotic induction and cell death. Additional studies revealed that rituximab treatment increased the internalization and degradation of the CD37-targeting antibody moiety of IMGN529. The combination of IMGN529 and rituximab was highly efficacious in multiple xenograft models, with superior antitumor efficacy seen compared to either agent alone or treatment with R-CHOP therapy. These findings suggest a novel mechanism whereby the potency of IMGN529 can be enhanced by CD20 binding, which results in the increased internalization and degradation of IMGN529 leading to the generation of greater amounts of cytotoxic catabolite. Overall, these data provide a biological rationale for the enhanced activity of IMGN529 in combination with rituximab and support the ongoing clinical evaluation of IMGN529 in combination with rituximab in patients with relapsed and/or refractory DLBCL.

2015-09-01·Current oncology reports2区 · 医学

Development and Integration of Antibody–Drug Conjugate in Non-Hodgkin Lymphoma

2区 · 医学

Review

作者: Andres Forero-Torres ; Amitkumar Mehta

Rituximab, a monoclonal antibody (MAb) against CD20, was the first MAb approved by the US Food and Drug Administration (FDA) for treatment of B cell non-Hodgkin lymphoma (B-NHL). Conjugating toxins to MAb was a technical challenge; however, with improvements in linker technology, immunoconjugates were constructed and revolutionized cancer treatment. Gemtuzumab ozogamicin was the first antibody drug conjugate (ADC) approved by the FDA. Because of the success of brentuximab vedotin and ado-trastuzumab emtansine in treating Hodgkin lymphoma (HL) and HER2-positive breast cancer, respectively, newer ADCs are being investigated. Brentuximab vedotin is approved for both HL and anaplastic large cell lymphoma. Newer ADCs, such as polatuzumab vedotin (targeting CD79b), pinatuzumab vedotin (targeting CD22), inotuzumab ozogamicin (targeting CD19), SAR3419 (targeting CD19), IMGN529 (targeting CD37), and SGN-CD19A (targeting CD19), have shown promising preclinical and early clinical activity. These findings will change the landscape of B-NHL treatment away from age-old "CHOP"-based chemotherapies.

项与 Naratuximab emtansine 相关的新闻（医药）

2023-08-17

·Pharmaceutical Technology

Ipsen gains FDA approval for fibrodysplasia ossificans progressiva therapy

Ipsen’s Sohonos has a specific selectivity for the gamma subtype of retinoic acid receptors. Credit: Ipsen Pharma. Ipsen has received approval from the US Food and Drug Administration (FDA) for its Sohonos (palovarotene) capsules to treat people with the ultra-rare bone disease, fibrodysplasia ossificans progressiva (FOP). It is approved as a retinoid to reduce the volume of new heterotopic ossification in adults and paediatric patients. Female patients must be eight years old and above to receive the treatment, and males must be at least ten. Recommended Reports Reports LOA and PTSR Model - Naratuximab Emtansine in Follicular Lymphoma GlobalData Reports LOA and PTSR Model - Saracatinib Difumarate in Fibrodysplasia Ossificans Progressiva (Myositis Os... GlobalData View all Companies Intelligence Ipsen SA View all The oral medicine Sohonos has a specific selectivity for the gamma subtype of retinoic acid receptors, which are skeletal development and ectopic bone regulators in the retinoid signalling pathway. Sohonos mediates the interactions between the receptors, growth factors and proteins, and lowers the formation of new abnormal bone in FOP sufferers. The FDA approval is based on the pivotal safety and efficacy data from the Phase III multicentre, open-label MOVE study in adult and paediatric patients. This included 107 patients who were administered oral palovarotene and compared with untreated individuals from the Ipsen worldwide FOP natural history study. The study showed that palovarotene successfully decreased the yearly volume of heterotopic ossification compared to no treatment beyond standard care. Ipsen research and development head Howard Mayer stated: ” Developing medicines for rare diseases takes commitment and belief from everyone involved. “We at Ipsen are sincerely grateful to the FOP community of patients and medical experts, as the first-ever treatment in the US for managing FOP would not be possible without their participation in the clinical trials and ongoing support.”

临床3期上市批准临床结果

2023-07-13

·Pharmaceutical Technology

FDA accepts BeiGene’s sNDA for follicular lymphoma therapy

BeiGene haematology chief medical officer Mehrdad Mobasher noted that Brukinsa is the first Bruton’s tyrosine kinase inhibitor to demonstrate efficacy in follicular lymphoma. Credit: BeiGene / Business Wire. The US Food and Drug Administration (FDA) has accepted for review BeiGene’s supplemental new drug application (sNDA) for Brukinsa (zanubrutinib) plus obinutuzumab to treat relapsed or refractory (R/R) follicular lymphoma (FL). The treatment is indicated for use in adult R/R FL patients, following a minimum of two previous lines of therapy. Recommended Reports Reports LOA and PTSR Model - Naratuximab Emtansine in Follicular Lymphoma GlobalData Reports LOA and PTSR Model - Atezolizumab in Follicular Lymphoma GlobalData View all Companies Intelligence BeiGene Ltd Rosewood Corp View all A decision on the approval for the treatment is expected in the first quarter of 2024. Brukinsa is a small molecule Bruton’s tyrosine kinase (BTK) inhibitor that received fast track and orphan drug designation for R/R FL treatment. The filing is based on findings from the Phase II ROSEWOOD clinical trial in 217 R/R non-Hodgkin FL patients, who had previously received treatment. Safety data from the trial were in line with those from prior studies of both therapies. Longer-term trial findings also showed that the efficacy benefit of Brukinsa plus obinutuzumab continued at a median follow-up of 20.2 months. BeiGene haematology chief medical officer Mehrdad Mobasher stated: “Follicular lymphoma is the most common slow-growing non-Hodgkin lymphoma, but there are limited treatment options for patients whose condition has progressed after two lines of therapy. “We are therefore pleased that Brukinsa is the first Bruton’s tyrosine kinase inhibitor to demonstrate efficacy in follicular lymphoma and plan to continue worldwide regulatory submissions based on the ROSEWOOD results.” The submissions for Brukinsa in the same indication are under review in China, Canada, Switzerland, the European Union and the UK. The latest development comes after the company entered a licence agreement for DualityBio’s antibody-drug conjugate therapy to treat certain solid tumours.

孤儿药引进/卖出临床结果临床2期快速通道

2023-05-08

·Pharmaceutical Technology

EC grants marketing approval for Chiesi, Protalix’s Fabry disease therapy

PRX-102 is indicated for the treatment of Fabry disease in adult patients. Credit: Pr Marie-Claire GUBLER, Paris, France / commons.wikimedia.org. The European Commission (EC) has granted marketing authorisation to Chiesi Global Rare Diseases and Protalix BioTherapeutics ’ PRX-102 (pegunigalsidase alfa) in the European Union (EU) to treat Fabry disease in adult patients. The PEGylated enzyme replacement therapy (ERT), PRX-102 is a plant cell culture-expressed, and chemically modified recombinant version of the α‑Galactosidase‑A enzyme. Recommended Reports Reports LOA and PTSR Model - Siremadlin Succinate in Myelofibrosis GlobalData Reports LOA and PTSR Model - Naratuximab Emtansine in Follicular Lymphoma GlobalData View all Companies Intelligence Chiesi Ltd Protalix BioTherapeutics Inc View all It was found to have a favourable circulatory half-life of about 80 hours, with targeted enzyme activity in organs that are affected by Fabry disease, in clinical trials. Chiesi Global Rare Diseases head Giacomo Chiesi said: “People living with Fabry disease often perceive their disease as burdensome and still experience unmet medical needs. “Our deepest gratitude to all patients and patient advocates who have stood shoulder-to-shoulder with clinical researchers, scientists, and regulators during the clinical development programme, providing the data needed for this approval.” The authorisation from EC was based on the data obtained from a comprehensive clinical development programme, which was conducted in over 140 patients, who received treatment for up to 7.5 years. The company stated that PRX-102 has been investigated in ERT-experienced and ERT-naïve patients, including in a head-to-head trial. It showed non-inferior efficacy to agalsidase beta in controlling the kidney disease, as assessed by the estimated glomerular filtration rate (eGFR) decline. Protalix BioTherapeutics president and CEO Dror Bashan said: “The European Commission’s approval of PRX-102 is a significant milestone for patients with Fabry disease and their families, providing a new therapeutic option. “Based on solid results from our robust clinical programmes, PRX-102 has the potential to be widely used for many years to come.”

上市批准

100 项与 Naratuximab emtansine 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15453

研发状态

适应症	最高研发状态	国家/地区	公司
慢性淋巴细胞白血病	临床2期	-	ImmunoGen, Inc. 更多
难治性非霍奇金淋巴瘤	无进展	瑞士更多	ImmunoGen, Inc. 更多
复发性非霍奇金淋巴瘤	无进展	瑞士更多	ImmunoGen, Inc. 更多
非霍奇金淋巴瘤	无进展	美国更多	ImmunoGen, Inc. 更多

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临床结果

适应症

分期

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT02564744 (ASCO2022)	临床2期	弥漫性大B细胞淋巴瘤	80	naratuximab emtansine (CD37 and CD20 positive cells)	鹽積範襯齋憲鏇醖遞艱(鬱繭選觸簾網鬱鏇糧築) = 鑰鹹觸餘繭遞鏇選壓廠壓膚簾構蓋遞範製淵鑰 (廠窪餘範顧範構顧築網, 64% ~ 82%)	-	2022-06-02
NCT02564744 (EHA2021)	临床2期	弥漫性大B细胞淋巴瘤	100	Naratuximab emtansine + Rituximab	選鑰繭廠夢憲願窪構遞(糧襯範糧願淵積繭齋齋) = 夢繭鑰範獵鹽製衊憲觸衊醖蓋願遞繭蓋選蓋蓋 (糧糧鏇築簾顧遞膚範蓋 )	-	2021-06-12
NCT01534715 (Pubmed \| Invest New Drugs) 人工标引	临床1期	B细胞淋巴瘤	49	IMGN529	膚窪膚鏇壓繭範壓積觸(積蓋糧窪鬱艱構鹹鏇醖) = eight patients and included peripheral neuropathy, febrile neutropenia, neutropenia, and thrombocytopenia 壓夢壓觸壓顧壓觸製鹽 (築醖糧衊鑰願築窪觸餘 ) 更多	积极	2018-10-01