Delving into the Latest Updates on Vantictumab with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

Anti-frizzled receptor monoclonal antibody, Anti-Fzd receptor monoclonal antibody, ANTI-FZD7

+ [3]

Target

Frizzled receptors

Mechanism

Frizzled receptors antagonists(Frizzled receptors antagonists)

Therapeutic Areas

NeoplasmsDigestive System DisordersEndocrinology and Metabolic Disease+ [2]

Active Indication

Breast CancerNon-Small Cell Lung CancerPancreatic Cancer

Inactive Indication

Metastatic breast cancer

Originator Organization

Mereo BioPharma 5, Inc.

Active Organization

Bayer AG

Inactive Organization

Mereo BioPharma 5, Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

Gene Sequence

Sequence Code 9645501L

Source: *****

Sequence Code 319372617H

Source: *****

Introduction: Wnt signaling is a signal transduction pathway that plays a vital role in embryonic development and normal tissue preservation. Dysfunction of it gives rise to various diseases like cancer, Alzheimer's, metabolic and skeletal disorders, kidney and liver disease, etc. Thus, targeting Wnt pathway can be a potential approach to design and develop novel therapeutic classes.Areas covered: Authors provided an overview of Wnt modulators from 2014 to 2020. Different heterocyclic scaffolds and their pharmacology from a total of 104 PCT applications have been summarized.Expert opinion: The scientific community is working extensively to bring first in the class molecule to the market which targets Wnt pathway. Lorecivivint, Wnt inhibitor, for the treatment of knee Osteoarthritis and SM-04554, Wnt activator, for the treatment of androgenetic alopecia are currently under Phase III. Other molecules, LGK-974, RXC-004, ETC-159, CGX-1321, PRI-724, CWP-232291 and BC-2059 are also under different stages of clinical development for the treatment of cancer. Antibody based Wnt modulator, OTSA101-DTPA-90Y is currently under Phase I for the treatment of Relapsed or Refractory Synovial Sarcoma while OMP-18R5 is under Phase I for Metastatic Breast Cancer. Ongoing preclinical/clinical trials will define the role of the Wnt pathway in different therapeutic areas and open new opportunities.

01 Nov 2020·Breast cancer research and treatmentQ2 · MEDICINE

Phase Ib clinical trial of the anti-frizzled antibody vantictumab (OMP-18R5) plus paclitaxel in patients with locally advanced or metastatic HER2-negative breast cancer

Q2 · MEDICINE

Article

Author: Mita, Alain ; Xu, Lu ; Zhang, Chun ; O'Shaughnessy, Joyce ; Osborne, Cynthia ; Diamond, Jennifer R ; Brachmann, Rainer K ; Kapoun, Ann M ; Richards, Donald ; Stagg, Bob ; Becerra, Carlos ; Henner, Randall ; Farooki, Azeez ; Mita, Monica ; Uttamsingh, Shailaja

PURPOSE:

Vantictumab is a monoclonal antibody that binds to frizzled (FZD) receptors and inhibits canonical WNT signaling. This phase Ib dose escalation study enrolled patients with locally recurrent or metastatic HER2-negative breast cancer who were treated with weekly paclitaxel in combination with escalating doses of vantictumab.

METHODS:

Patients were enrolled in dose escalation cohorts treated with weekly paclitaxel 90 mg/m² on days 1, 8 and 15 in combination with vantictumab 3.5-14 mg/kg days 1 and 15 or 3-8 mg/kg day 1 of every 28-day cycle. Primary endpoints were safety, dose-limiting toxicities (DLTs). Secondary endpoints included pharmacokinetics, efficacy and an exploratory biomarker analysis.

RESULTS:

Forty-eight female patients with a mean age of 54 were enrolled. The majority (66.6%) received prior chemotherapy for recurrent or metastatic disease; 45.8% were hormone receptor (HR)-positive, HER2-negative and 54.2% triple-negative. The most frequent adverse events related to any study treatment were nausea (54.2%), alopecia (52.1%), fatigue (47.9%), and peripheral neuropathy (43.8%). No DLTs occurred; however, 6 patients experienced fractures outside of the DLT window. The overall response rate was 31.3% and the clinical benefit rate was 68.8%. A 6-gene WNT pathway signature showed significant association with progression-free survival (PFS) and overall survival (OS) for the biomarker high versus biomarker low groups (PFS: p = 0.029 and OS: p = 0.00045, respectively).

CONCLUSIONS:

The combination of vantictumab and weekly paclitaxel was generally well tolerated with promising efficacy; however, the incidence of fractures limits future clinical development of this particular WNT inhibitor in metastatic breast cancer.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov registration: NCT01973309.

01 Jun 2020·Investigational new drugsQ3 · MEDICINE

A phase 1b dose escalation study of Wnt pathway inhibitor vantictumab in combination with nab-paclitaxel and gemcitabine in patients with previously untreated metastatic pancreatic cancer

Q3 · MEDICINE

Article

Author: O'Neil, Bert H ; Berlin, Jordan ; Dotan, Efrat ; Cardin, Dana B ; Shahda, Safi ; Lenz, Heinz-Josef ; Davis, S Lindsey ; Kapoun, Ann M ; Cohen, Steven J ; Stagg, Robert J ; Messersmith, Wells A

Summary:

Vantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. This phase Ib study evaluated vantictumab in combination with nab-paclitaxel and gemcitabine in patients with untreated metastatic pancreatic adenocarcinoma. Patients received vantictumab at escalating doses in combination with standard dosing of nab-paclitaxel and gemcitabine according to a 3 + 3 design. A total of 31 patients were treated in 5 dosing cohorts. Fragility fractures attributed to vantictumab occurred in 2 patients in Cohort 2 (7 mg/kg every 2 weeks), and this maximum administered dose (MAD) on study was considered unsafe. The dosing schedule was revised to every 4 weeks for Cohorts 3 through 5, with additional bone safety parameters added. Sequential dosing of vantictumab followed by nab-paclitaxel and gemcitabine was also explored. No fragility fractures attributed to vantictumab occurred in these cohorts; pathologic fracture not attributed to vantictumab was documented in 2 patients. The study was ultimately terminated due to concerns around bone-related safety, and thus the maximum tolerated dose (MTD) of the combination was not determined. The MAD of vantictumab according to the revised dosing schedule was 5 mg/kg (n = 16).

100 Deals associated with Vantictumab

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External Link

KEGG	Wiki	ATC	Drug Bank
D10410	-	-	DB12956

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Metastatic breast cancer	Phase 1	US	Mereo BioPharma 5, Inc.	01 Sep 2013
Pancreatic Cancer	Phase 1	US	Mereo BioPharma 5, Inc.	01 Sep 2013
Breast Cancer	Phase 1	-	Bayer AG	-
Non-Small Cell Lung Cancer	Phase 1	US	Mereo BioPharma 5, Inc.	-
Non-Small Cell Lung Cancer	Phase 1	-	Bayer AG	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01973309 (Pubmed \| Breast Cancer Res) Manual	Phase 1	Metastatic HER2-Negative Breast Carcinoma HER2-negative	48	paclitaxel+vantictumab	ijxoghiyfs(cpxkwmbivn) = kyhjmecqwf nkexbifxay (agopcosnnc ) View more	Positive	01 Nov 2020
NCT02005315 (Pubmed \| Invest New Drugs) Manual	Phase 1	Secondary malignant neoplasm of pancreas First line	31	nab-paclitaxel+gemcitabine+vantictumab	dgxhkscfuj(poeuesskbt) = not determined icznaitosd (yxtvjjtdvv ) View more	Negative	01 Jun 2020
NCT02005315 (ASCO_GI2019)	Phase 1	Pancreatic Cancer	31	Vantictumab + Nab-P + G	zfrgifutel(qjbacxsjrw) = grade 3 dehydration in 1 of 9 patients in cohort 4 (5 mg/kg q4w) sxtfgvqswc (ukvlmkwiam ) View more	Negative	29 Jan 2019
NCT01973309 (ASCO2016)	Phase 1	Metastatic HER2-Negative Breast Carcinoma	23	Paclitaxel	pibgwkxkxt(pzirmgkzzq) = n = 3 lthpnoydlw (sflggzhgop ) View more	-	20 May 2016