Roche submits US FDA application for 'T-DM1'

BASEL, Switzerland — Roche announced recently that it submitted a Biologics License Application (BLA) to the US Food and Drug Administration (FDA) for trastuzumab-DM1 (T-DM1) in people with advanced HER2-positive breast cancer who have previously received multiple HER2-targeted medicines and chemotherapies.

This submission is based on the results of a Phase II study, which showed T-DM1 shrank tumors in one-third of women who had received on average seven prior medicine for advanced HER2-positive breast cancer.

“While we have made great strides in treating HER2-positive breast cancer, there is a group of people whose breast cancer will come back after many treatments, leaving them with very limited options,” said Dr. Hal Barron, global development and chief medical officer.

“Data from studies have shown that T-DM1 shrank tumors in these people, so we are excited to have submitted this application to the FDA in hopes of offering a potential new medicine to people with this type of breast cancer,” Barron said.

T-DM1 is an antibody-drug conjugate (ADC), also known as an armed antibody, being studied for advanced HER2-positive breast cancer. 

T-DM1 attaches trastuzumab and the chemotherapy DM1 together using a stable linker, which is designed to keep T-DM1 in one piece until it reaches specific cancer cells.

The antibody (trastuzumab) binds to the HER2-positive cancer cells, and is thought to block out-of-control signals that make the cancer grow while also calling on the body’s immune system to attack the cells. 

Then, once T-DM1 is absorbed into those cancer cells, it is designed to destroy them by releasing the DM1.

The FDA submission is based on a Phase II study known as TDM4374g, a single-arm, multi-center trial designed to assess single-agent T-DM1 in 110 women with HER2-positive advanced breast cancer whose disease had worsened after receiving at least two prior HER2-targeted treatments (trastuzumab and lapatinib) in the metastatic setting, as well as an anthracycline, a taxane and capecitabine. 

The primary endpoint of the study was objective response rate (a complete or partial tumor shrinkage of at least 30 percent, determined by two tumor assessments at least 28 days apart), as measured by an independent review facility.

Roche licenses technology for T-DM1 under an agreement with ImmunoGen Inc. 

Building on successes with T-DM1, Roche has approximately 50 ADCs in early stages of research and development for multiple tumor types.

Breast cancer is the most common cancer among women worldwide. Each year more than one million new cases of breast cancer are diagnosed worldwide, and nearly 400,000 people will die of the disease annually.