Advancing Knowledge of Disease Biology to Optimize Lung Cancer Treatment

As part of a visit to Columbia University Irving Cancer Research Center, CancerNetwork^® spoke with Brian Henick, MD, about the future of the lung cancer field and how clinicians can continue to optimize therapeutic outcomes among patients. Although the field has seen a “range of success” for targeting EGFR mutations, ALK alterations, and other markers across different lung cancer populations, Henick described a need to further understand disease biology to help develop new therapies for other patient subgroups, such as those with TP53-mutated disease.

According to Henick, investigators at Columbia University plan to evaluate an investigational therapy that targets ULBP-2/5/6 while directing T cells to this protein set. He also noted “promising effects” with new treatment classes such as antibody drug conjugates, which have even demonstrated potential benefits in patients with squamous cell carcinomas.

Henick is a medical oncologist specializing in the care of patients with malignancies of the aerodigestive tract and the director of the Phase I Unit and of Translational Research in Aerodigestive Cancers in Medical Oncology at Columbia University Herbert Irving Comprehensive Cancer Center.

Transcript:

We’re lucky in that we may have the beginnings of a blueprint already in place, at least in terms of nonsquamous lung cancer or adenocarcinoma. What we have there is basically a pie of cancers that gets divided by alterations in the genes that drive the cancers. Each driver genetic alteration has its own classes of therapies that seem to be beneficial. It causes many of us in the field to feel like these are separate diseases. In some cases, you have a patient where they have a cancer that grew in their lung; you look under the microscope, and it looks like adenocarcinoma. We know that when that problem arises because of a mutation in the EGFR gene, that’s going to point us in the direction of targeted therapies. On the other hand, if we see a mutation in the TP53 gene and we don’t see anything else, we’re not able to target it in the same way.

One of the great quests in the field in the last number of decades has been to try to find all the different driver events that can happen in lung cancer and to try to find therapies associated with them. There’s a range of success we see for EGFR, ALK, and for certain other [mutations]. [There are] wonderful therapies that work very well for years for patients to be able to achieve almost a normal quality of life. On the other hand, there are examples where we’ve not made as much progress. What it comes down to is trying to improve our understanding of the biology, of what’s happening to the cancer in each of those situations.

One concept that’s exciting to us here at Columbia is the idea of a protein that might be unique to squamous cancers, [which] can be targeted with a new therapy. We have a study that’s due to open soon with a company called Evolveimmune, and they have therapy that is designed to target a set of proteins called ULBP-2/5/6 and bring T cells to that protein. That therapy is structured in such a way that one arm goes after this protein that’s elevated in squamous cancers, and the other arm is designed to draw in T cells. We’re hoping to have open that study here in the next couple of months, and that would be a very interesting proof of concept for a therapy that might work across a range of solid tumors.

Similarly, we do see promising effects in emerging classes of therapies like antibody drug conjugates. There are some that have shown promise in squamous cell carcinomas. There are other bispecific antibodies, for example, targeting EGFR, which can be amplified in squamous cancers that seem to be showing promise and may be moving towards approvals in the coming months or years.