Delving into the Latest Updates on Ensituximab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Ensituximab (USAN/INN)

+ [2]

Target

MUC5AC

Mechanism

MUC5AC inhibitors(Mucin-5AC inhibitors)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease

Active Indication

Colorectal CancerPancreatic Cancer

Inactive Indication

Metastatic Colorectal CarcinomaPancreatic Cancer, AdultMetastatic Pancreatic Cancer

Originator Organization

Neogenix Oncology, Inc.

Active Organization

The Sidney Kimmel Comprehensive Cancer Center

Neogenix Oncology, Inc.

Inactive Organization

Precision Biologics, Inc.

Drug Highest PhasePhase 2

First Approval Date-

RegulationOrphan Drug (US)

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Structure/Sequence

Sequence Code 319372697L

Source: *****

Sequence Code 319372629H

Source: *****

This is a randomized phase II multi-institution prospective open label study in which up to 90 subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer who previously received treatment with chemotherapy with FOLFIRINOX or FOLFIRINOX-like regimen will be enrolled into one of two arms:
A: NPC-1C with gemcitabine and nab-paclitaxel or B: gemcitabine and nab-paclitaxel

Start Date01 Apr 2013

Sponsor / Collaborator

Precision Biologics, Inc.

NCT01040000

/ CompletedPhase 1/2

A Phase 1/2 Therapeutic, Open Label, Multi-Center Clinical Trial of NPC-1C, a Chimeric Monoclonal Antibody, in Adults With Recurrent, Locally Advanced Unresectable or Metastatic Pancreatic and Colorectal Cancer After Standard Therapy

The purpose of the phase 2 component of this study is to determine if giving the immune molecule NPC-1C to individuals who have cancer of the pancreas or gastrointestinal tract (colon or rectum) which has not responded to standard treatments can shrink or halt the growth of cancer, and to obtain additional data to study its effect on the immune system. Safety data will also be accumulated and evaluated during this study. NPC-1C is a monoclonal antibody that recognizes a specific tumor target on certain cancers. In laboratory studies, the antibody killed tumor cells in some colon and pancreatic cancers that express the NPC-1C antigen by a process called "antibody-dependent cell cytotoxicity" or ADCC.

Start Date01 Jan 2012

Sponsor / Collaborator

Precision Biologics, Inc.

ACTRN12607000448448

/ Active, not recruitingPhase 2

A Phase 2 Two-Center, Randomized, Double-blind, Placebo-controlled, Paired Treatment Site Comparison Study to Evaluate the Safety and Preliminary Efficacy of a Topical Antimicrobial (NEO101) in Reduction of Wound Bioburden among Adults Treated with Curettage & Electrodessication for Superficial Basal Cell Carcinomas of the Trunk and Extremities

Start Date10 Sep 2007

Sponsor / Collaborator

Neosil, Inc.

100 Clinical Results associated with Ensituximab

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100 Translational Medicine associated with Ensituximab

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100 Patents (Medical) associated with Ensituximab

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7

Literatures (Medical) associated with Ensituximab

15 Jul 2020·Clinical Cancer ResearchQ1 · MEDICINE

Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer

Q1 · MEDICINE

Article

Author: Mahipal, Amit ; Kim, Richard D. ; Mavroukakis, Sharon A. ; Azad, Nilofer S. ; Tan, Benjamin ; Zaki, Anjum ; Torrealba, Jose ; Fantini, Massimo ; Tsang, Kwong Y. ; Arlen, Philip M. ; Poplin, Elizabeth ; Beg, Muhammad S. ; Morse, Michael A.

AbstractPurpose:Patients with metastatic colorectal cancer refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal cancer.Patients and Methods:Single-arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed MUC5AC antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required on the basis of the assumption that ensituximab would improve median overall survival (OS) by 7 months using a one-sided significance level of 10% and 80% power. Written informed consent was obtained from all patients.Results:Sixty-three patients with advanced, refractory colorectal cancer were enrolled and 53 subjects were treated in phase II arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment-related adverse events (AE) at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%), and diarrhea (6%). Serious AEs at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin, and hypoxia. No patients discontinued treatment due to drug-related AEs.Conclusions:Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal cancer.

01 Sep 2016·Cancer Chemotherapy and PharmacologyQ4 · MEDICINE

A phase 1 dose-escalation study of NEO-102 in patients with refractory colon and pancreatic cancer

Q4 · MEDICINE

Article

Author: Azad, Nilofer S ; Morse, Michael A ; Arlen, Philip M ; Mavroukakis, Sharon ; Beg, Muhammad S ; Patel, Sandip P ; Torrealba, Jose ; Wang, Xue Ping ; Beatson, Melony A

PURPOSENEO-102 is a novel chimeric IgG1 monoclonal antibody which recognizes a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumors. Preclinical models have demonstrated encouraging signs of anti-tumor activity through antibody-dependent cell-mediated cytotoxicity.METHODSThis is a phase 1, dose-escalation trial of NEO-102 (Ensituximab) for patients with refractory pancreatic and colorectal cancer. The primary objective was to determine safety and tolerability of escalating doses of NEO-102. Secondary objectives were to assess pharmacokinetics, anti-tumor activity and biologic correlates. Patients whose tumors express NPC-1 antigen were eligible. Dose-escalation was performed in a 3 + 3 design at doses of 1.5, 2, 3 and 4 mg/kg.RESULTSA total of 19 patients (4 pancreatic and 15 colon cancer) were enrolled at participating institutions in the treatment phase. Most common treatment-related adverse events included anemia, fatigue, fevers, chills and flushing. There was no detectable hemolysis. Of twelve patients evaluable for disease response, the response rate at week 8 included 5 patients with stable disease and 8 patients with progressive disease (PD). Treatment-related grade 3/4 hyperbilirubinemia and anemia were observed at 4 mg/m2. Reversible hypoxia at 3 mg/kg was a dose-limiting toxicity. The maximum tolerated dose was established at 3 mg/kg. Of 74 patients who underwent tissue screening, positive NPC-1 expression was 47 % in colon and 59 % in pancreatic cancer.CONCLUSIONSTreatment with the NEO-102, in this first-in-human study, is well tolerated with a manageable safety profile. A maximum tolerated dose of 3 mg/kg has been established. Toxicity profile is typical for this therapeutic class and allows for combination with conventional cytotoxic therapies.

10 Mar 2014·JOP : Journal of the pancreas

Novel agents for the treatment of pancreatic cancer.

Author: Muhammad Wasif Saif ; Gregory T Brennan ; Valerie Relias

Metastatic pancreatic cancer continues to be a difficult disease to treat because of its aggressive nature, advanced stage at presentation and lack of treatment options. There is a need for the development of new agents directed against novel targets to improve outcomes for these patients. At the 2014 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium phase I/II trials provided information on three novel strategies for treating metastatic pancreatic cancer. Immunotherapy in the form of a vaccine (GVAX) followed with an immune stimulator (CRS-207) showed extended survival (Abstract #177). A monoclonal antibody (NEO-102) targeting MUC5AC also showed activity and was well tolerated (Abstract #243). A heat shock protein 90 (HSP90) inhibitor (ganetespib) showed modest effects but was well tolerated making it available for use with conventional chemotherapy (Abstract #297). The details of these presentations will be discussed.

1

News (Medical) associated with Ensituximab

06 Nov 2024

·www.prnewswire.com

Precision Biologics to Announce Development of New Monoclonal Antibody (mAb) PB-223 at SITC, Houston, TX, November 7-8, 2024

Precision Biologics will present affinity maturation and characterization of a novel core 2 O-glycan epitope targeting anti-human carcinoma mAb PB-223 at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024 BETHESDA, Md., Nov. 6, 2024 /PRNewswire/ -- Precision Biologics, Inc. reports that affinity maturation and characterization of its novel anti-core 2 O-glycan monoclonal antibody PB-223, will be presented in a poster at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting on November 7-8, 2024, George R. Brown Convention Center, Houston, Texas, USA, Poster title: Affinity Maturation and Characterization of a Novel O-glycan Epitope Targeting Anti-Human Carcinoma Monoclonal Antibody (mAb) PB-223 Presentation of the poster will be made in person on the following dates and locations: November 7th, 2024: SITC Immune Engineering Workshop, 3.10 p.m-5 p.m. CST, George R. Brown Convention Center, Level 3 - Grand Ballroom AB, Houston, Texas, USA November 8th, 2024: Poster Session Immuno-Engineering, abstract number 1101, 12:15–1:45 p.m. CST and 5:30-7 p.m. CST, George R. Brown Convention Center, Level 1-Exhibit Halls A B, Houston, Texas, USA BACKGROUND: PB-223 is an innovative mAb developed through immune engineering from the chimeric IgG1 NEO-102 (Ensituximab). It targets a unique core 2 O-glycan (variant of MUC5AC), Preclinical and clinical data showed that NEO-102 specifically binds to and kills colorectal and pancreatic cancer cells through ADCC. NEO-102 did not bind to healthy tissues. In a phase 2 study, NEO-102 showed promising results in heavily pretreated patients with advanced, refractory metastatic colorectal cancer. In general, the efficacy of using a monoclonal antibody as a single agent in cancer immunotherapy can be impaired not only by the resistance of cancer cells in the tumor microenvironment (TME), but also by a low binding affinity to target antigens expressed on cancer cells. One strategy to improve the therapeutic efficacy of monoclonal antibodies is to enhance their binding affinity to target antigens. STUDY PRESENTED AT SITC 2024: The objective of this study was to enhance the binding affinity of NEO-102 to its target antigen. By engineering the VH and VL sequences of NEO-102 through Fast Screening for Expression Biophysical Properties and Affinity (FASEA), while maintaining the binding specificity to the target antigen, allowed us to develop a new clone with a lower KD and markedly improved characteristics. This new biologic asset developed by affinity maturation was given the name PB-223. Binding kinetics of PB-223 and NEO-102 to the target antigen were compared by ELISA. Results show that PB-223 has a KD of 4.5-fold less than NEO-102, suggesting a higher affinity for the target antigen by PB-223 compared to NEO-102. The binding affinity of PB-223 and NEO-102 to various human tumor cell lines was also evaluated by flow cytometry. Flow cytometry analysis showed that PB-223 not only has markedly enhanced comparative binding to colorectal and pancreatic cancer cell lines recognized by NEO-102, but that PB-223 is also able to bind to many additional tumor cell lines that were not recognized by NEO-102. Further study by O-glycan array analysis showed that 1) PB-223 binds specifically to core-2 O-glycans, and that 2) core 2 O-glycans recognized by PB-223 are expressed on tumor cell lines positive for PB-223 binding in flow cytometry. Immunohistochemistry (IHC) analysis performed on human tumor tissues shows that PB-223 does not bind to healthy tissues. IHC analysis also shows that PB-223, in addition to binding to both colorectal cancer and pancreatic cancer, it also binds to additional tumor tissues not reactive with NEO-102, including triple negative breast cancer, prostate cancer, kidney cancer, head and neck cancer, liver cancer, and bladder cancer. In addition, this study demonstrated that PB-223 is internalized into human cancer cell lines expressing core 2 O-glycans. Findings from this study suggest that PB-223 has a strong binding affinity for human cancers expressing core 2 O-glycans and that PB-223 may be a potential candidate for the development of antibody-drug conjugates (ADC) for treatment of various human carcinomas. The PDF of the poster will be available starting from November 5, 2024, at the following link: SOURCE Precision Biologics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultImmunotherapyPhase 2AACR

100 Deals associated with Ensituximab

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External Link

KEGG	Wiki	ATC	Drug Bank
D09898	Ensituximab	-	DB12342

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic Colorectal Carcinoma	Phase 2	US	Precision Biologics, Inc.	01 Jan 2012
Metastatic Pancreatic Cancer	Phase 2	US	Precision Biologics, Inc.	01 Jan 2012
Colorectal Cancer	Phase 2	-	Neogenix Oncology, Inc.	-
Pancreatic Cancer	Phase 2	-	Neogenix Oncology, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01834235 (Pubmed)	Phase 2	Advanced Pancreatic Ductal Adenocarcinoma Second line	78	Gemcitabine plus nab-paclitaxel	(nzcgvcuguq) = xmvpkhnmom vjcnkcvqpf (zfgbxclhvn ) View more	-	03 Jan 2023
NCT01834235 (Pubmed)	Phase 2	Advanced Pancreatic Ductal Adenocarcinoma Second line	78	Gemcitabine plus nab-paclitaxel and NPC-1C	(nzcgvcuguq) = hcmhlcarag vjcnkcvqpf (zfgbxclhvn ) View more	-	03 Jan 2023
NCT01834235 (AACR2022) Manual	Phase 2	Pancreatic Cancer Second line	80	Ensituximab+gemcitabine+Albumin-Bound Paclitaxel	(jwraasxdmh) = haluybhqge mwpqxwlzxn (udhhjtilyb, 3.3 - 6.5) View more	Negative	15 Nov 2022
NCT01834235 (AACR2022) Manual	Phase 2	Pancreatic Cancer Second line	80	gemcitabine+Albumin-Bound Paclitaxel	(jwraasxdmh) = bwcrnptyif mwpqxwlzxn (udhhjtilyb, 4.7 - 8.4) View more	Negative	15 Nov 2022
NCT01040000 (Pubmed \| Clin Cancer Res) Manual	Phase 2	Colorectal Cancer	63	Ensituximab	(pthndhbpiq) = aznvfqrmsc qlqypmaivg (tvdludzwlm ) View more	Positive	15 Jul 2020
NCT01040000 (ASCO2017)	Phase 1/2	Metastatic colon cancer	63	Ensituximab	(xfbjywtbwl) = dhkivmvwht npsoajvebb (gtahxnjzyw, 5.39 - 8.02) View more	Positive	30 May 2017
NCT01040000 (NEO-102, ASCO_GI2016)	Phase 2	Metastatic colon cancer	47	NEO-102	(libehcnjcr) = ptpzakfany vjynzabnkp (bwxtybsbkl ) View more	Positive	01 Feb 2016
NCT01040000 (ASCO2015)	Phase 2	Refractory Colorectal Carcinoma	43	NEO102 (N)	(tlgxwzozvo) = qaigvklaaq dwxygvtmmb (ednztbqybu )	-	20 May 2015
NCT01040000 (ASCO_GI2015)	Phase 1/2	Refractory Cancer	94	NEO102	(bwencqvpdf) = kvatfubaix pnxlfrkqfq (vzvsendgdt ) View more	-	20 Jan 2015
AACR2013	Phase 1	Colorectal Cancer \| Pancreatic Cancer	15	NPC-1C	(ssygowtlnk) = kfwahcevaf yxiwuihcfs (gdnpyvigtx )	-	15 Apr 2013
ASCO2012	Phase 1	Colorectal Cancer \| Pancreatic Cancer	15	NPC-1C	(sdgkplxors) = mhmrnztkzm dcsbvkaoca (drybtzwepl )	-	20 May 2012
ASCO_GI2012	Phase 1/2	Colorectal Cancer \| Pancreatic Cancer	-	NPC-1C	(bnsjwsqcrb) = ixkiankedv osxxokdwby (gqrawgtaod )	-	01 Feb 2012