Investigators Release Positive Results From Clinical Trials of Cellular Immunotherapies

The analyses are shared at the American Association for Cancer Research Annual Meeting 2022 in New Orleans, Louisiana.

Investigators reported positive results from 4 clinical trials of cellular immunotherapies at the American Association for Cancer Research (AACR) Annual Meeting 2022 in New Orleans, Louisiana.

In the first trial, investigators combined a chimeric antigen receptor T-cell therapy (CAR-T) with an mRNA vaccine (CARVac) that showed the combination, BTN211, had an acceptable safety profile.

The phase 1 trial results showed more robust engraftment in individuals who received the combination therapy compared with CAR-T cells alone.

Additionally, the CAR-T therapy showed early signs of efficacy, both as a monotherapy and in combination with CARVac in individuals with testicular and other carcinoembryonic antigen claudin-6 (CLDN6)-positive solid tumors.

CLDN6 is virtually absent in healthy adult tissues and is expressed in endometrial, lung, ovarian, testicular, and other solid cancers.

Approximately 70% had manageable cytokine release syndrome (CRS) symptoms with lipase enzyme elevations. The lipase elevations were asymptomatic, and an ultrasound found no evidence of pancreatitis.

Among the 14 individuals evaluated for efficacy, investigators found an ORR of 43% and a disease control rate of 86% at 6 weeks after infusion. They also found a deepening of initial partial response at 12 weeks after infusion.

In a second study, investigators found manageable toxicity and early signs of clinical activity in individuals with H3K27M-mutated diffuse midline glioma after sequential intravenous (IV) and intracerebroventricular delivery of GD2-CAR T cells.

Adverse events (AEs) included hydrocephalus and CRS following IV infusion, both of which were manageable.

Future trials will integrate patient-reported outcomes to further results on treatment impact.

In a third trial, investigators found that natural killer (NK) cells derived from stored umbilical cord blood and treated with the bispecific innate call engager AFM13, which binds both CD30 on cancer cells, and CD16A on NK cells, showed good antitumor response for individuals with refractory or relapsed CD30+ lymphomas.

They also found that the xenograft mouse models of CD30+ lymphomas showed that precomplexing cord blood NK cells with AFM13 can facilitate CAR-like responses and improve cytotoxic effects.

The individuals in the study received 3 infusions of AFM13 CAR-like NK cells over a 3-week period. The primary endpoint was safety and recommended dose of NK cells. The secondary endpoints included response rates, persistence of infused cells, and survival.

The highest dosage in the trial was established as the recommended maximum dose.

Among the 19 individuals, the ORR was 89.5% and responses were observed in all individuals who received the maximum dose level.

After a median follow up of 9 months, the overall-survival rate was 81% and event-free survival was 52%.

In a fourth study, investigators discussed the approval for axicabtagene ciloleucel for recurrent or refractory large B-cell lymphoma after 2 or more lines of systemic therapy.

The ZUMA-7 trial showed that axicabtagene ciloleucel was superior to the standard-of-care platinum-based chemotherapy. The median event-free survival was 8.3 months in individuals who received axicabtagene ciloleucel compared with 2 months for those who received chemotherapy.

The ORR was 83% and 50%, respectively, and the complete response rate was 65% and 32%, respectively.

“We saw peak concentration of axi-cel 1 week after infusion, with a steady decline toward baseline levels, which were reached by month 3, although a few patients have low but detectable levels at later time points,” Jason Westin, MD, MS, from MD Anderson Cancer Center, who presented the session at the AACR Annual Meeting 2022, said in a statement. “The CAR-T cell levels were associated significantly with both objective responses and with neurological toxicity.”

Additionally, CAR-T cell expansion did not predict durability of the response, but the state of the CAR-T cells did. The quality of the T-cells mattered more than the quantity.

Reference

Positive results reported from four clinical trials of cellular immunotherapies. American Association for Cancer Research Meeting News. April 12, 2022. Accessed April 13, 2022. https://www.aacrmeetingnews.org/news/positive-results-reported-from-four-clinical-trials-of-cellular-immunotherapies/