Tag: antibodies

Company News: Micromet Initiates Global Phase 2 Trial of Blinatumomab in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia

Micromet, Inc. (NASDAQ: MITI) today announced that it has initiated a phase 2 trial of its lead product candidate blinatumomab (MT103) in adult patients with relapsed or refractory (r/r) B-precursor acute lymphoblastic leukemia (ALL). Blinatumomab is the first of a new class of agents called BiTE® antibodies, designed to harness the body’s T cells to kill cancer cells.

This phase 2, single-arm study will evaluate the efficacy and safety of blinatumomab in approximately 65 patients with relapsed/refractory Philadelphia-negative B-precursor ALL. Patients will receive blinatumomab daily for 28 days followed by two weeks off blinatumomab over a six week treatment cycle. Patients who achieve a complete remission (CR) or complete response without full recovery of platelets (CRh*) within two cycles of treatment will receive up to three additional cycles of consolidation treatment. The primary endpoint of the study is CR/CRh*. Secondary endpoints include duration of response and overall survival. The study will be conducted at approximately 40 leading cancer centers in the U.S. and EU. The Company currently expects to complete enrollment in this trial by year end 2012.

Additional information regarding this Phase 2 study is available at the U.S. government’s clinical trials database at http://www.clinicaltrials.gov.

Blinatumomab Clinical Experience in Adult R/R ALL

Interim results from a Phase 2 trial presented at the 2011 Meeting of the European Hematology Association show that blinatumomab produced a high CR rate in adult patients with ALL who had relapsed following treatment with standard therapy. 75% of patients (9 of 12) achieved a CR or CRh* following treatment with blinatumomab1. All nine responding patients achieved a complete molecular response, or had no evidence of leukemic cells in their bone marrow, a key prognostic factor for patient survival. Notably, four patients with genetic abnormalities typically associated with poorer outcomes all achieved a CR or CRh*. The most common clinical adverse events were fever, peripheral edema and fatigue. Treatment of two of the twelve patients was interrupted due to fully reversible and manageable central nervous system (CNS) events.

Company News: Micromet’s BiTE Antibodies Overcome Cancer Cell Resistance

In several clinical trials, antibody company Micromet has demonstrated outstanding efficacy and safety of its bispecific BiTE antibodies which come with two binding sites: one for a cancer target and a second one for a T cell. As a result, T cells are recruited and guided directly to the tumor cell, initiating cancer cell death in a serial fashion.

In this week’s PNAS, researchers of the company demonstrate that the BiTE antibodies also can overcome the notorious resistance against conventional monoclonal antibodies arising in many cancer patients.

The researchers converted the anti-EGFR antibodies cetuximab (Erbitux) and panitumumab (Vectibix) into BiTE antibodies by adding the binding site for T cells. In animal models, these BiTE antibodies then showed a remarkably high potency (in the sub-picomolar range) against cancer cells with KRAS and BRAF-mutations which made them resistant to the original monoclonal antibodies.

According to the authors, “the present study shows that conversion of EGFR-specific monoclonal antibodies cetuximab and panitumumab into T cell-engaging BiTE antibodies is technically feasible and that the BiTE technology can overcome resistance of KRAS- and BRAF- mutated CRC lines to the therapeutically used parental antibodies. The simplest explanation for the latter is that T cell-engaging BiTE antibodies do not rely on inhibition of EGFR signaling but use the receptor tyrosine kinase as mere surface anchor for attachment of cytotoxic T cells. This function of BiTE antibodies is not expected to be affected by mutations of downstream components of the EGFR pathway that obviate the cancer cell’s dependence on the EGFR surface receptor for delivery of growth-promoting signaling.”

If this holds up in clinical trials, it is not only good news for patients with resistance to conventional cancer antibodies already on the market, but it will also provide an opportunity for a whole range of new cooperations with pharma companies for product enhancement and life cycle management.