Roger Li, MD, on Bladder Cancer: Boosting Immune Checkpoint Blockade With an Oncolytic Adenovirus
Roger Li, MD, of the H. Lee Moffitt Cancer Center, discusses results from a phase II single-arm study of CG0070, a cancer-selective oncolytic adenovirus that creates mechanistic synergy with immune checkpoint blockade. In this trial, the virus was combined with pembrolizumab in patients with non–muscle-invasive bladder cancer that is unresponsive to bacillus Calmette-Guérin. At 3 months, 88% of the 35 patients enrolled achieved a complete response (Abstract 666).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The purpose of our study was to look at the efficacy of combination CG0070, which is an oncolytic adenovirus, along with immune checkpoint blockade, in the setting of BCG-unresponsive CIS-containing non-muscle invasive bladder cancer. The BCG-unresponsive space has been well described, but it's a very difficult to treat disease in which the standard of care is surgical removal of the bladder. Because the disease takes place in a cohort of patients who are older and frail, it's unfit. That procedure is unfit, unfortunately, for many of the patients, because it's fraught with a lot of complications. Hence, there is a critical, unmet need for efficacious bladder-sparing therapies.
We hypothesized that the combination of CG0070, along with immune checkpoint, can engender an efficacious anti-tumor immunogenic response that can help patients preserve their bladders, and set out to test this hypothesis.
In the study, we enrolled 35 patients and out of the first 32 evaluable patients, we looked at the primary endpoint, which is the 12-month complete response rate. And of the first 15 patients who had reached that endpoint, we're seeing a 73% complete response rate at one year. In the entire cohort, there were just under 90% of the patients who had reached the complete response by the three-month mark. And those numbers compared to pembro alone were much better. Whereas the pembro alone cohort had achieved only a 40% complete response at three months and 20% complete response by one year. So we're seeing a really synergistic effect between the virus and pembrolizumab together, and in addition to that, we're also seeing a tolerable toxicity profile where the combination really didn't have any surprises in terms of toxicity, with essentially just added toxicity from the two agents put together.
As a next step, we're really looking forward to launching a randomized control trial where we're testing the combination of the two agents against pembrolizumab alone in this disease setting to really show that it's more efficacious than the monotherapy agent.
Jonathan Chen, MD, PhD, of Massachusetts General Hospital, discusses “immunity hubs” that interact with a reservoir of stem-like CD8 T cells and appear to be associated with subsequent response to anti–PD-1 blockade in patients with non–small cell lung cancer. Hybrid hubs, Dr. Chen says, are a favorable class of immunity hub notable for CD8-positive and TCF7-positive cells, as well as CCL19 expression (Abstract 956).
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).
Talal El Zarif, MD, of Dana-Farber Cancer Institute, and Abdul Rafeh Naqash, MD, of Stephenson Cancer Center at The University of Oklahoma, discuss the results of their cohort study of patients living with HIV and metastatic non–small cell lung cancer, who are often underrepresented in clinical trials, and the safety and efficacy of treating this unique population with immune checkpoint inhibitors (ICIs). The data showed that patients living with HIV and lung cancer had similar toxicity profiles and clinical outcomes as did those who did not have HIV and received ICIs (Abstract 437).
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).
Wade T. Iams, MD, of Vanderbilt University Medical Center, discusses phase II efficacy results from the first-line non–small cell lung cancer cohort of the TACTI-002 study. The results suggest that when combined with pembrolizumab, eftilagimod alpha yielded encouraging efficacy across all PD-L1 levels, including patients with PD-L1 low and PD-L1 negative disease (Abstract 1470).