Kim A. Reiss Binder, MD, spoke about the phase 1 CARISMA trial which investigated CAR macrophages in HER2-overexpressing solid tumors.
Kim A. Reiss Binder, MD, assistant program director of the Hematology/Oncology Fellowship Program at Penn Medicine and assistant professor of medicine at the Hospital of the University of Pennsylvania, spoke with CancerNetwork® at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, about the phase 1 CARISMA trial (NCT04660929) of the first-in-class HER2-targeted chimeric antigen receptor macrophage (CAR M) therapy CT-0285 being investigated in patients with HER2-overexpressing solid tumors. The trial showed that a best overall response was found in 4 of 7 patients on the trial as well as no serious dose-limiting toxicities.
This study [was not conducted to confirm] efficacy, but it would be nice if in the first 18 patients we did see some efficacy. Currently, we have a few patients who had stable disease as their best response, that’s at least encouraging. What we’ve shown, and this is highlighted in the poster, is the translational work that’s been done alongside the clinical work. This is showing that the macrophages get there, that they induce inflammation, and that there are changes in T-cell repertoire, which are all good things that we want to see. The second question is, how can we make this work better? The team has done some nice preclinical studies with PD-1 inhibitors plus CAR M that look very promising. I suspect that one of the next steps will be combining anti-PD-1 therapy with CAR M to see if we can improve upon our efficacy.
I hope that people who treat patients with pancreatic cancer see that there is some forward movement and hope for developing maintenance strategies for patients who have had a response after a few months of chemotherapy, largely because we’ve all had patients in the clinic who do exceptionally well with chemotherapy but at the cost of the quality of their lives. What I hope the takeaway from the PARP [inhibitor] and ICB [immune checkpoint blockade] study is that there is now an opportunity outside of just patients with DDR deficiency to get something like that. Future study in that area is going to be critical for patients. From the CAR M perspective, it is encouraging to see not only a brand-new therapy that’s feasible to use and safe, although the data as you said is early, but that what we’re seeing translationally is that the CAR Ms get where they we’re expecting them to get to and that there is a response in terms of T cell and inflammation. There’s potential there to expand and move down the road and you may see more of CAR M in the future in different incarnations as time goes by.
Reiss KA, Yuan Y, Ueno NT, et al. A phase 1, first-in-human (FIH) study of the anti-HER2 CAR macrophage CT-0508 in subjects with HER2 overexpressing solid tumors. J Clin Oncol. 2022;40(suppl 16):2533. doi: 10.1200/JCO.2022.40.16_suppl.2533