Trial explores T-cell therapy’s role in personalized treatment for lung cancer
ATLANTA — In the battle against non-small cell lung cancer, the ability to personalize treatment may be a key to victory, according to Karen Reckamp, MD, co-director of the lung cancer and thoracic oncology program at City of Hope.
Reckamp is the lead investigator of a phase 1 clinical trial examining a novel T-cell therapy for the treatment of NSCLC, the details of which she presented at American Association for Cancer Research Annual Meeting.
Reckamp spoke to HemOnc Today about why this combination of engineered T cells and PD-1/PD-L1 inhibitor therapy may have promise for the treatment of NSCLC and solid tumors in general.
Question: What was your research group’s rationale for conducting this trial ?
Answer: It goes back to the emergence of effective immunotherapy for NSCLC, and now small cell lung cancer. NSCLC was one of the first tumors to get approval for PD-1 and PD-L1 inhibitors in solid tumors. Although these drugs are good for a number of patients, still only a minority of patients have long-term benefit.
Genetically engineered T cells have shown responses in hematological malignancies and curative potential in some patients who are highly refractory. In tumors that have not been effectively treated by PD-1/PD-L1 inhibitors, this strategy may improve the ability of T cells to create an antitumor response. By genetically engineering these cells, we introduce specific T cells that are primed toward the tumor — and hopefully will add to the antitumor immune effect.
Q: What about this clinical trial’s methodology makes it novel compared with previous research?
A: This is a phase 1B trial (NCT03709706) looking at both safety and efficacy. Some of the earlier trials looked at the engineered T cells alone, trying to understand the safety and efficacy of the cells in patients with solid tumors. This trial is moving into combination therapy with pembrolizumab (Keytruda, Merck), so that we are taking away the blockade of PD-1/PD-L1 and stimulating T-cell responses.
Q: What are the key points of the trial?
A: Importantly, NY-ESO-1 autologous T cells have shown benefit in sarcoma, which moves the potential treatment forward. The trial includes those with LAGE-1a antigen, which increases the number of patients who could be eligible. By adding pembrolizumab, we are inhibiting the PD-1/PD-L1 blockade and priming the T cells. We are hoping to move engineered T-cell therapy into the solid tumor space — especially into NSCLC.
Q: Why do you think NSCLC has such a poor response to current treatments?
A: NSCLC has historically developed resistance to treatment relatively quickly, and the resistant cells are more difficult to treat. We have learned over the years that there are many different types of NSCLC. Nonsmokers, especially those with EGFR alterations, will likely not benefit as much from PD-1/PD-L1 therapy. We are always trying to enhance our ability to improve immunotherapy for all patients.
For example, our squamous cell patients tend to have better responses to immunotherapy but don’t have responses to targeted therapy in general. It’s really about personalizing the treatment to the patient’s tumor, and by engineering these T cells to specific tumor antigens, we move toward personalized treatment with immunotherapy.
Q: Do you believe that T-cell immunotherapies hold promise for the treatment of solid tumors?
A: I do. For decades we have been trying to harness the immune system to attack solid tumors, without much benefit. The advent of PD-1/PD-L1 and CTLA-4 checkpoint inhibitors has helped us to realize that we can use the immune system to fight solid tumors. Using mechanisms like engineered T cells may help us to bring benefit to more patients.
Q: How would you describe the trial enrollment process thus far?
A: Because patients need to be tested for [human leukocyte antigen (HLA)] and matched by HLA and tested for NY-ESO-1 and LAGE-1a, there is a large screening process. We are very, very active in screening patients. Very few will move forward to the actual treatment.
Q: How do you initiate a discussion with patients about participating in a trial like this one?
A: Because of the press that CAR T-cell therapy has received, I have a lot of patients coming to me asking for these types of therapies. These are really the ‘home run’ type of trials. They are not looking for a small benefit, they are looking for a remarkable benefit. Patients are actively engaged in these types of discussions. When we talk about the potential for participating in a trial like this, most patients are interested in starting the screening process.
Q: Do you have a timeline for any preliminary trial results?
A: No — that I do not have right now.
Q: Anything else you wish to get across about this research and its potential?
A: It’s early on in the trial, but I think this is an exciting new area for solid tumors in general, and specifically for NSCLC. – by Drew Amorosi
Reckamp KL, et al. Abstract CT225. Presented at: AACR Annual Meeting; March 29-April 3, 2019; Atlanta.
For more information:
Karen Reckamp, MD, can be reached at City of Hope, Medical Oncology Department, 1500 E. Duarte Road, Duarte, CA, 91010; email: email@example.com.
Disclosure: GlaxoSmithKline, in collaboration with Merck, funded the study. Reckamp reports grant and research support to her institution from AbbVie, Acea Biosciences, Adaptimmune, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, Loxo Oncology, Molecular Partners, Xcovery and Zeno; and honoraria from Tesaro.