Delving into the Latest Updates on MEDI-3726 with Synapse

Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

ADCT 401, ADCT-401, MEDI 3726

Target

DNA x PSMA

Action

inhibitors

Mechanism

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

Therapeutic Areas

NeoplasmsUrogenital Diseases

Active Indication-

Inactive Indication

Metastatic castration-resistant prostate cancerProstatic Cancer

Originator Organization

MedImmune LLC

Active Organization-

Inactive Organization

MedImmune LLC

ADC Therapeutics SA

License Organization-

Drug Highest PhaseDiscontinuedPhase 1

First Approval Date-

Regulation-

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Structure/Sequence

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A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.

The purpose of this study is to assess the safety and tolerability, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI3726 in subjects with mCRPC who have received prior treatment with abiraterone or enzalutamide, with or without a prior taxane-based chemotherapy in the mCRPC setting.

Start Date06 Jan 2017

Sponsor / Collaborator

MedImmune LLC

100 Clinical Results associated with MEDI-3726

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100 Translational Medicine associated with MEDI-3726

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100 Patents (Medical) associated with MEDI-3726

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9

Literatures (Medical) associated with MEDI-3726

01 Mar 2022·Prostate cancer and prostatic diseasesQ2 · MEDICINE

Advances in PSMA-targeted therapy for prostate cancer

Q2 · MEDICINE

Review

Author: Li, Zhifeng ; Wang, Fujin ; Feng, Xiaoqian ; 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 Jul 2021·Clinical cancer research : an official journal of the American Association for Cancer ResearchQ1 · MEDICINE

Phase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody–Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide

Q1 · MEDICINE

Article

Author: He, Peng ; Martinez, Pablo ; Liang, Meina ; Williams, Marna ; Zhang, Qu ; Cathomas, Richard ; Rosenbaum, Anton I. ; Miralles, Manuel Selvi ; Vashisht, Kapil ; Petrylak, Daniel P. ; Hinrichs, Mary Jane ; Wang, Judy S. ; de Bono, Johann S. ; Fleming, Mark T. ; Bothos, John ; Cho, Song

Abstract:

Purpose::

MEDI3726 is an antibody–drug conjugate targeting the prostate-specific membrane antigen and carrying a pyrrolobenzodiazepine warhead. This phase I study evaluated MEDI3726 monotherapy in patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.

Patients and Methods::

MEDI3726 was administered at 0.015–0.3 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary objective was to assess safety, dose-limiting toxicities (DLT), and MTD/maximum administered dose (MAD). Secondary objectives included assessment of antitumor activity, pharmacokinetics, and immunogenicity. The main efficacy endpoint was composite response, defined as confirmed response by RECIST v1.1, and/or PSA decrease of ≥50% after ≥12 weeks, and/or decrease from ≥5 to <5 circulating tumor cells/7.5 mL blood.

Results::

Between February 1, 2017 and November 13, 2019, 33 patients received MEDI3726. By the data cutoff (January 17, 2020), treatment-related adverse events (TRAE) occurred in 30 patients (90.9%), primarily skin toxicities and effusions. Grade 3/4 TRAEs occurred in 15 patients (45.5%). Eleven patients (33.3%) discontinued because of TRAEs. There were no treatment-related deaths. One patient receiving 0.3 mg/kg had a DLT of grade 3 thrombocytopenia. The MTD was not identified; the MAD was 0.3 mg/kg. The composite response rate was 4/33 (12.1%). MEDI3726 had nonlinear pharmacokinetics with a short half-life (0.3–1.8 days). The prevalence of antidrug antibodies was 3/32 (9.4%), and the incidence was 13/32 (40.6%).

Conclusions::

Following dose escalation, no MTD was identified. Clinical responses occurred at higher doses, but were not durable as patients had to discontinue treatment due to TRAEs.

01 Feb 2021·Journal of the science of food and agricultureQ2 · AGRICULTURAL & FORESTRY SCIENCE

Dietary supplementation of extracts of red sea weed (Kappaphycus alvarezii) improves growth, intestinal morphology, expression of intestinal genes and immune responses in broiler chickens

Q2 · AGRICULTURAL & FORESTRY SCIENCE

Article

Author: Prasad, Cadaba Srinivas ; Rama Rao, Savaram V ; Kumar, Vikas ; Nori, Sri Sailaja ; Vantharam Venkata, Hemanth Giri Rao ; Perveen, Zeba ; Paul, Shyam Sundar ; Raju, Mantena VLN ; Suryanarayan, Shrikumar

Abstract:

BACKGROUND:

Effects of supplementation of dried alkaline (referred to as MVP1) and aqueous (referred to as PBD1) extracts of Kappaphycus alvarezii, were evaluated in broiler (Vencobb 400) chickens (1–35 days post‐hatch). In experiment I, each of the seven diets (basal diet with three levels (0.5, 1.5 or 5.0 g kg−1 diet) of MVP1 or PBD1 and a negative control was fed to 12 pen replicates containing five birds in each. In experiment II, each of three diets [a negative control, and PBD1 at two levels (1.0 or 1.5 g kg−1 diet)] was fed to 16 pen replicates of five chicks in each.

RESULTS:

Concentrations of total phenolics, phycobillins and free radical scavenging activity were higher (P < 0.01) whereas carrageenan was lower in PBD1 than in MVP1. In the experiment I, PBD1 at 1.5 g kg−1 diet improved (P < 0.05) body weight (BW) (7.11% higher). In the experiment II, both the treatments improved (P < 0.01) BW (9.18% and 8.47%, respectively) compared to the control. The group fed with PBD1@ 1.0 g kg−1 had higher (P < 0.05) haemagglutination inhibition titre, expression of intestinal claudin 2, TLR2A, NOD1, avian beta defensin 4, interleukin 2 and interleukin 6 genes than control. Treatments did not influence feed efficiency or levels of most of the antioxidant enzymes. Villus width and crypt depth were significantly higher in the group fed with 1.5 g kg−1 of PBD1.

CONCLUSION:

100 Deals associated with MEDI-3726

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic castration-resistant prostate cancer	Phase 1	United States	MedImmune LLC	06 Jan 2017
Metastatic castration-resistant prostate cancer	Phase 1	Switzerland	MedImmune LLC	06 Jan 2017
Metastatic castration-resistant prostate cancer	Phase 1	United Kingdom	MedImmune LLC	06 Jan 2017
Prostatic Cancer	Phase 1	-	ADC Therapeutics SA	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02991911 (AACR2021 \| Clin Cancer Res) Manual	Phase 1	Metastatic castration-resistant prostate cancer	33	MEDI3726	ffugomrjvo(wnkxygmuek) = drowmhxwhm ejoqumdcla (fecxfhxeuf ) View more	Positive	01 Jul 2021
NCT02991911 (ASCO_GU2020)	Phase 1	Castration-Resistant Prostatic Cancer	33	MEDI3726	kdjshfpapy(weqejglhkm) = vzimshjbsy cjqmkpiovg (claabfqjwi ) View more	Negative	19 Feb 2020

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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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