Delving into the Latest Updates on MLN 591-DM1 with Synapse

Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

MLN 591-DM1 conjugate, MLN 2704, MLN 591-DM1

+ [2]

Target

PSMA x Tubulin

Action

inhibitors

Mechanism

PSMA inhibitors(Prostate-specific membrane antigen inhibitors), Tubulin inhibitors

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication-

Inactive Indication

Castration-Resistant Prostatic CancerProstatic Cancer

Originator Organization

ImmunoGen, Inc.

Active Organization-

Inactive Organization

Millennium Pharmaceuticals, Inc.

ImmunoGen, Inc.

License Organization-

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

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The purpose of the study is to determine the highest dose of MLN2704 that can be given multiple times safely to patients with prostate cancer, and to identify any side effects associated with taking the drug. This study will also evaluate how MLN2704 is taken up, broken down and eliminated by the body.

Start Date01 Oct 2003

Sponsor / Collaborator

Millennium Pharmaceuticals, Inc.

NCT00052000

/ CompletedPhase 1

A Phase 1 Single Ascending Dose Trial of MLN2704 (DM1 Conjugated Monoclonal Antibody MLN591) in Subjects With Metastatic Androgen Independent Prostate Cancer

This is the first study of MLN2704 administered to humans. The purpose of the study is to determine the highest dose of MLN2704 that can be given safely to patients with prostate cancer, and to identify any side effects associated with taking the drug. This study will also evaluate how MLN2704 is taken up (absorbed), broken down (metabolized) and eliminated (excreted) by the body. This process is called pharmacokinetic analysis.

Start Date01 Nov 2002

Sponsor / Collaborator

Millennium Pharmaceuticals, Inc.

100 Clinical Results associated with MLN 591-DM1

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100 Translational Medicine associated with MLN 591-DM1

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100 Patents (Medical) associated with MLN 591-DM1

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8

Literatures (Medical) associated with MLN 591-DM1

01 Mar 2022·Prostate cancer and prostatic diseasesQ2 · MEDICINE

Advances in PSMA-targeted therapy for prostate cancer

Q2 · MEDICINE

Review

Author: Li, Zhifeng ; Feng, Xiaoqian ; Wang, Fujin ; Yang, Dazhuang ; Lin, Mei

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein located on the cell membrane, is specifically and highly expressed in prostate cancer (PCa). Besides, its expression level is related to tumor invasiveness. As a molecular target of PCa, PSMA has been extensively studied in the past two decades. Currently, a great deal of evidence suggests that significant progresses have been made in the PSMA-targeted therapy of PCa. Herein, different PSMA-targeted therapies for PCa are reviewed, including radioligand therapy (¹⁷⁷Lu-PSMA-RLT, ²²⁵Ac-PSMA-RLT), antibody-drug conjugates (MLN2704, PSMA-MMAE, MEDI3726), cellular immunotherapy (CAR-T, CAR/NK-92, PSMA-targeted BiTE), photodynamic therapy, imaging-guided surgery (radionuclide-guided surgery, fluorescence-guided surgery, multimodal imaging-guided surgery), and ultrasound-mediated nanobubble destruction.

01 Sep 2021·Current opinion in oncologyQ3 · MEDICINE

Antibodies targeting Prostate-Specific Membrane Antigen positive prostate cancer: from diagnostic imaging to theranostics

Q3 · MEDICINE

Review

Author: Aoun, Fouad ; Mjaess, Georges ; Roumeguère, Thierry ; Albisinni, Simone

Purpose of review:

Targeting Prostate-Specific Membrane Antigen (PSMA) has paved the way for personalized medicine in prostate cancer (PCa) patients. This review aims to highlight the role of PSMA targeting antibodies in PCa, for diagnostic and therapeutic purposes.

Recent findings:

PSMA Positron Emission Tomography/Computed Tomography has been a game changer in the diagnosis of PCa in the recent decade. Two anti-PSMA monoclonal antibodies have been studied in PCa: 7E11-C35 (limited use) and J591. J591 antibody was used for diagnostic purposes coupled with different radionuclides. Most importantly, it was combined to numerous therapeutic radionuclides such as Lutetium-177 (177Lu), Yttrium-90 (90Y), Indium-111 (111In), and Actinium-225 (225Ac). It was also conjugated to drugs forming antibody-drug conjugates (e.g. MLN2704 and PSMA-ADC). These compounds were tested in recent phase I/II clinical trials.

Summary:

PSMA targeting antibodies are very promising for further clinical investigation and continue to be a momentous research area, for both imaging and therapeutic settings. Although some clinical trials resulted in unfavorably safety profiles for some antibodies, they validated PSMA as a crucial immunoconjugate target.

01 Dec 2016·Urologic oncologyQ3 · MEDICINE

Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer

Q3 · MEDICINE

Article

Author: Iain J. Webb ; Neil H. Bander ; Matthew D. Galsky ; Daniel J. George ; Robert Dreicer ; Jesika Petruck ; Kin Tse ; Michael J. Morris ; David M. Nanus ; Howard I. Scher ; Daniel J. Crona ; Matthew I. Milowsky

BACKGROUND:

This phase 1/2 study evaluated the dose-limiting toxicity and maximum tolerated dose of MLN2704, a humanized monoclonal antibody MLN591 targeting prostate-specific membrane antigen, linked to the maytansinoid DM1 in patients with progressive metastatic castration-resistant prostate cancer.

PATIENTS AND METHODS:

A total of 62 patients received MLN2704 at ascending doses on 4 schedules: weekly (60, 84, 118, and 165mg/m²; 12 patients); every 2 weeks (120, 168, 236, and 330mg/m²; 15 patients); every 3 weeks (330 and 426mg/m²; 18 patients); and on days 1 and 15 of a 6-week schedule (6-week cycle, 330mg/m²; 17 patients). The primary efficacy endpoint was a sustained ≥50% decline from baseline prostate-specific antigen (PSA) without evidence of disease progression. Toxicity, pharmacokinetics, immunogenicity, and antitumor activity were assessed.

RESULTS:

Neurotoxicity was dose-limiting. Overall, 44 patients (71%) exhibited peripheral neuropathy: 6 (10%) had grade 3/4. Neurotoxicity rates remained high despite increasing the dosing interval to 3 (13 of 14; one grade 3) and 6 weeks (16 of 17; three grade 3). MLN2704 pharmacokinetics were dose-linear. Rapid deconjugation of DM1 from the conjugated antibody was seen. In all, 5 patients (8%) experienced ≥50% decline in PSA; 5 (8%) had PSA stabilization lasting≥90 days. Only 2 of 35 patients on the 3- and 6-week schedules achieved a PSA decline of >50%.

CONCLUSIONS:

MLN2704 has limited activity in metastatic castration-resistant prostate cancer. Disulfide linker lability and rapid deconjugation lead to neurotoxicity and a narrow therapeutic window.

100 Deals associated with MLN 591-DM1

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Castration-Resistant Prostatic Cancer	Phase 2	United States	Millennium Pharmaceuticals, Inc.	01 Oct 2003
Prostatic Cancer	Phase 2	-	ImmunoGen, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00070837 (Pubmed \| Urol Oncol) Manual	Phase 1/2	Metastatic castration-resistant prostate cancer	62	MLN2704	zfwjmngfjk(epwpvrkrce) = mfprvhyzur fiwkhsdvaq (epbqdbviad ) View more	Negative	01 Dec 2016
ASCO2005	Phase 1/2	Metastatic castration-resistant prostate cancer	21	MLN2704	cptfbnkbrz(ejzsrzaspr) = enrgnyzirt hcanpylcuy (rgzjzrhuby )	-	01 Jun 2005
ASCO2004	Phase 1	Metastatic Prostate Carcinoma	23	MLN2704	bbkmxhswmr(owswdkycky) = ytswxyztpu saxuxygmtd (jsghukwalq )	-	15 Jul 2004

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Translational Medicine

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Clinical Trial

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Approval

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Biosimilar

Competitive landscape of biosimilars in different countries/locations. Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3.

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