Health

The Role of Bispecific Antibody Therapy in Lung Cancer

Treatment with the EGFR-MET bispecific antibody amivantamab (Rybrevant) combined with the investigational third-generation EGFR tyrosine kinase inhibitor (TKI) lazertinib led to one complete response and 12 partial responses in 45 patients with EGFR-mutated non-small cell lung cancer (NSCLC) in a study presented at the 2021 virtual American Society of Clinical Oncology (ASCO) annual meeting.

In this video, courtesy of VJHemOnc, Benjamin Besse, MD, PhD, of Gustave Roussy Cancer Institute in Paris, outlines the future role of bispecific antibody therapy for treating lung cancer.

Following is a transcript of his remarks:

When you refer to bispecific, you have to differentiate two big different categories of drugs. First of all, you have a category of bispecific that will address two different targets on the same cancer cell. An example of that is amivantamab — it’s a bispecific antibody that targets EGFR and MET on the tumor cell. So let’s say that there is no direct interaction with the immune system, the drug has been shown to be very active, and the data have been presented at the ASCO conference this year.

Amivantamab is used either alone or combined with an EGFR inhibitor. So it’s interesting because you can have the double blockade of the EGFR by the TKI and by one antibody, plus the blockade of c-MET by the bispecific antibody. And it works. Response rate in patients pre-exposed to amivantamab was 36%, with a PFS [progression-free survival] of 4.6 months. The drugs are currently evaluated in a phase III trial in France compared to osimertinib. So clearly a very interesting way to fight cancer.

The second big family of bispecific … that combine two different targets on two different family of cells: the first target will be the cancer cell, and the second target will be the immune cell. So you can find different names, T-cell engager, for example. So let’s say that it’s really a mechanism that forces the immune system to fight the cancer cells. I like to call them the ARD immunotherapies, and in a way they are not so far from the CAR T cells.

These are a family of drugs with more specific side effects, let’s say maybe stronger side effects … mostly CRS [cytokine release syndrome]. For example, there was some interesting data on the bispecific antibody T-cell engager against the LL3, the target that is frequently expressed in small cell lung cancer. Here the drug caused some CRS in 44% of the patients, could be some grade 3 or more for some in the 66 patients that were treated. But very interesting, the overall response rate was 20% in a population where we know that it’s very hard to get an efficacy signal, a disease as hard to treat as small cell lung cancer.

So probably we will have to refine the way we manage the new toxicities of these agents, but I’m pretty sure that that will be also part of the treatment that we will use in the future.

  • Greg Laub joined MedPage Today in 2005 as Production Manager and led the launch of the video department in 2007. He is currently responsible for the website’s video production. Follow

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