Delving into the Latest Updates on Bivatuzumab mertansine with Synapse

Overview

Basic Info

Drug Type

Antibody drug conjugate (ADC)

Synonyms

Anti-CD44v6-DM1 immunoconjugate, Monoclonal antibody CD44v6-DM1 immunoconjugate

Target

CD44v6 x Tubulin

Mechanism

CD44v6 inhibitors(CD44v6 inhibitors), Tubulin inhibitors, Apoptosis stimulants

+ [1]

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal Diseases

Active Indication

Metastatic breast cancerAdvanced Head and Neck Squamous Cell Carcinoma

Inactive Indication-

Originator Organization

ImmunoGen, Inc.

Active Organization

Boehringer Ingelheim GmbH

Inactive Organization

ImmunoGen, Inc.

Drug Highest PhasePhase 1

First Approval Date-

Regulation-

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Structure

Molecular FormulaC14H16N2O4S2

InChIKeyGTBCXYYVWHFQRS-UHFFFAOYSA-N

CAS Registry341498-08-6

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Gene Sequence

Sequence Code 1116885906L

Sequence Code 68624H

BACKGROUND AND PURPOSETo test whether BIWI 1 (bivatuzumab mertansine), an immunoconjugate of the humanized anti-CD44v6 monoclonal antibody BIWA 4 and the maytansinoid DM1, given simultaneously to fractionated irradiation improves local tumour control in vivo compared with irradiation alone.MATERIAL AND METHODSFor growth delay, FaDu tumours were treated with 5 intravenous injections (daily) of phosphate buffered saline (PBS, control), BIWA 4 (monoclonal antibody against CD44v6) or BIWI 1 (bivatuzumab mertansine) at two different dose levels (50 μg/kg DM1 and 100 μg/kg DM1). For local tumour control, FaDu tumours received fractionated irradiation (5f/5d) with simultaneous PBS, BIWA 4 or BIWI 1 (two dose levels).RESULTSBIWI 1 significantly improved local tumour control after irradiation with 5 fractions already in the lower concentration. The dose modifying factor of 1.9 is substantial compared to the majority of other modifiers of radiation response.CONCLUSIONBecause of the magnitude of the curative effect, this approach is highly promising and should be further evaluated using similar combinations with improved tumour-specificity.

01 Sep 2008·Oral OncologyQ2 · MEDICINE

Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma

Q2 · MEDICINE

Article

Author: Alexander Sauter ; Silke Gronau ; Gertraud Hanft ; Thomas Erhardt ; Herbert Riechelmann ; Carsten Schroen ; Karl Hoermann ; Wolfram Golze

CD44v6 is a tumor associated antigen abundantly expressed in head and neck squamous cell carcinomas (HNSCC) and in normal squamous epithelium. The immunoconjugate bivatuzumab mertansine (BIWI 1) consists of a highly potent antimicrotubule agent coupled to a monoclonal antibody against CD44v6. The maximum tolerated dose (MTD), safety and efficacy of BIWI 1 administered IV in patients with HNSCC has not been determined. In a clinical phase I trial, adult patients with recurrent or metastatic HNSCC were treated intravenously with BIWI 1. Starting with 25mg/m(2), the dose was escalated in steps of 25mg/m(2) until dose limiting toxicity was observed. Six women and 25 men were included. The MTD was 300 mg/m(2). Twelve patients were treated with at least the MTD. The principal toxic effects were maculopapular rashes, focal blister formation and skin exfoliation. Three patients had partial responses at doses of 200, 275 and 325 mg/m(2). The concept that bivatuzumab can direct mertansine activity to CD44v6 expressing tumors was confirmed. Although CD44v6 was abundantly expressed in all tumors, the response to BIWI 1 was variable. Binding to CD44v6 on skin keratinocytes mediated serious skin toxicity with a fatal outcome in a parallel trial, which led to the termination of the development program of bivatuzumab mertansine and the present study.

01 Apr 2007·Anti-Cancer DrugsQ4 · MEDICINE

Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study

Q4 · MEDICINE

Article

Author: Schmidt, Peter ; Schneeweiss, Andreas ; Lauschner, Ilka ; Sinn, Hans-Peter ; Staab, Alexander ; Sohn, Christof ; Schuetz, Florian ; Hanft, Gertraud ; Rupp, Ute ; Schoendorf-Holland, Eva ; Eichbaum, Michael ; Huober, Jens

The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer. Anthracycline and taxane-pretreated patients with metastatic breast cancer that expressed CD44v6 received one single infusion of bivatuzumab mertansine and were observed for 21 days within one treatment course. Starting dose was 25 mg/m, while dose was escalated by increments of 25 mg/m. Patients who experienced a disease stabilization were eligible for further courses with bivatuzumab mertansine. Blood serum samples were taken throughout the treatment period for pharmacokinetic analysis. Twenty-four patients were treated at eight different dose levels (25-200 mg/m), seven of these patients received more than one course of bivatuzumab mertansine. Two dose-limiting toxicities occurred: one patient treated with 125 mg/m developed transient National Cancer Institute Common Toxicity Criteria grade 4 elevation of liver enzymes; another patient treated at 175 mg/m experienced National Cancer Institute Common Toxicity Criteria grade 3 vomiting. She died from renal failure, which might have been caused by deterioration of pre-existing renal insufficiency. The most common toxicities were transient and mild skin disorders in 75% of patients. As a consequence of one fatal toxic epidermal necrolysis that occurred in a study running in parallel, the clinical trials programme of bivatuzumab mertansine was discontinued. None of the patients developed antibodies against bivatuzumab mertansine. No objective responses were observed. Disease stabilization was achieved in 50% of patients independently of dose level. In conclusion, bivatuzumab mertansine targets CD44v6 and appears to stabilize heavily pretreated metastatic breast cancer that expresses CD44v6. The maximum tolerated dose could not be determined in this trial as the sponsor discontinued the clinical development of bivatuzumab mertansine.

100 Deals associated with Bivatuzumab mertansine

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Bivatuzumab mertansine	-	-

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Phase 1	-	Boehringer Ingelheim GmbH	01 Jul 2003
Metastatic breast cancer	Phase 1	-	Boehringer Ingelheim GmbH	01 Oct 2002
Advanced Head and Neck Squamous Cell Carcinoma	Phase 1	-	Boehringer Ingelheim GmbH	01 Sep 2002
Head and Neck Neoplasms	Phase 1	-	ImmunoGen, Inc.	-