Sumanta Pal, MD, on Renal Cell Carcinoma: CRISPR-Engineered CAR T Cells in Advanced Disease
Sumanta Pal, MD, of the City of Hope Comprehensive Cancer Center, discusses phase I results from the COBALT-RCC study, a first-in-human clinical trial exploring CD70 CAR T-cell therapy in patients with clear cell renal cell carcinoma. The agent appeared to show an excellent safety profile with no unexpected toxicities and antitumor activity. One durable complete response is the first to be achieved with allogeneic CAR T-cell therapy in patients with relapsed or refractory solid tumors, offering proof of concept for further exploration of CD70-targeted CAR T cells in renal cell and other CD70-positive malignancies (Abstract 558).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Renal cell carcinoma, we have an exciting array of available therapies, including VEGF inhibitors and checkpoint inhibitors. The challenge for us though is that it's a small fraction of patients that are actually cured of their disease. With that in mind, it's really critical that we look to new treatments and new pathways, and actually cell therapy represents one of those potential avenues.
We usually think about cell therapies in the context of liquid tumors, for instance, myeloma and lymphoma, but the COBALT-RCC study sought out to test whether or not CTX130, which is an allogeneic CD70 directed CAR-T cell, could potentially have an impact in this disease. CD70 is a target that's very pervasively expressed in renal cell carcinoma. It's also expressed in some cutaneous T-cell lymphomas as well.
So the COBALT-RCC study included patients who had actually received one prior VEGF inhibitor, one prior PD1 or PD-L1 inhibitor, and thereafter, they were allowed to potentially participate in the trial. Patients in this study were actually quite heavily pretreated. Patients received CTX 130. As I'd mentioned, it's an allogeneic CAR-T cell directed at CD70 with a couple of key edits.
We actually removed CD70 from the cell to prevent fratricide, the T-cell receptors removed and MHC1 is removed as well. There's also a locus, of course, that's anti-CD70. In the study, patients were allowed to receive lymphative bleeding chemotherapy with Fludarabine and Cytoxan. They thereafter received CTX130 as a onetime infusion. Patients were allowed to re-dose, and ultimately, we enrolled a total of 14 patients that we presented [inaudible 00:01:49].
I was really impressed with the fact the toxicities we experienced were very limited. About half of patients had grade one to two CRS, but we didn't have any grade three CRS events. There was no ICANS or graft versus host disease. And one thing that is incredibly, incredibly exciting, and this I think is really going to hopefully bring a lot of attention to this type of therapy in the field, is that we had a patient who actually achieved a complete response. Not only that, but this complete response has actually been durable.
The complete response has lasted now for a total of two years. There's an array of other patients in the study who achieve stable disease as a best response. And again, I think we're looking forward to developing this therapy in the future as a later version, CTX131, with some additional edits that we think are going to enhance activity and also enhance efficacy. With that, I think the future is bright for cell therapies and renal cell carcinoma.
Michael A. Postow, MD, of Memorial Sloan Kettering Cancer Center, discusses new findings on the correlation between CD8 cell PET imaging with zirconium-89–crefmirlimab berdoxam and CD8 cell immunohistochemistry in patients with advanced cancer receiving immunotherapy. Noninvasive CD8 PET scanning with crefmirlimab berdoxam permits whole-patient, longitudinal CD8 assessment, which is currently under investigation as a biomarker for immunotherapy responsiveness and may be a useful tool for immunotherapy development and clinical management (Abstract 1472).
Antoni Ribas, MD, PhD, of the University of California, Los Angeles, discusses a phase I study that used CRISPR gene editing to simultaneously “knock out” endogenous T-cell receptors and replace them with personalized neoantigen T-cell receptors in patients with solid tumors. The edited TCR T-cell products were safely infused and trafficked to the tumor lesions (Abstract 1478).
Kishu Ranjan, PhD, of Yale University School of Medicine, discusses his study findings, which identified a deficiency in the biomarker TAP2 as a prominent immune evasion mechanism in patients whose non–small cell lung cancer has resisted immunotherapy (Abstract 148).
David Reardon, MD, of Dana-Farber Cancer Institute, discusses phase I/II results from the EOGBM1-18/ROSALIE study, which showed the EO2401 vaccine plus nivolumab generated systemic immune responses correlating with efficacy in patients with recurrent glioblastoma. Adding bevacizumab to this combination appeared to improve efficacy. (Abstract 642).
Julia Tchou, MD, PhD, of the University of Pennsylvania, discusses preliminary results of the phase Ib/II BreastVax study, which suggested a single preoperative pembrolizumab dose plus a tumor-targeting radiation boost may result in pathologic response in patients with early-stage triple-negative breast cancer (Abstract 644).