Syncona/Woodford investment Autolus reports positive data – Claire Roddie MB, PhD, FRCPath, honorary senior lecturer, Cancer Institute, University College London, has presented initial data from the ongoing Phase 1/2 trial of AUTO1 in adult acute lymphoblastic B cell leukemia (ALL). the presentation was made at the American Association of Cancer Research Annual Meeting 2019 in Atlanta, Georgia.
Initial results from the trial show an 88% molecular complete response (no sign of cancer) at one month with a well-tolerated safety profile. Relapsed / refractory B-cell acute lymphoblastic leukemia in adults is an area of significant unmet clinical need. Autolus’s approach uses the bodies immune system to attack the cancer cells. No similar CAR T cell therapy has been approved for adults with the condition. The key challenges identified in clinical studies testing this therapy are considerable toxicity associated with severe cytokine release syndrome and high-grade neurological toxicity.
AUTO1 uses a novel binder that allows the CAR T cells to disengage rapidly after an encounter with a target cell and kill. Data from the ongoing trial of AUTO1 in pediatric acute lymphoblastic leukemia (presented in February 2019) showed that AUTO1 has a well-tolerated safety profile without inducing high grade cytokine release syndrome in pediatric patients.
In the adult trial, as at 18 March 2019, products for 12 patients were manufactured, including seven with Autolus’ semi-automated, fully enclosed manufacturing process. Two patients are yet to be treated (“pending infusion”). Among the 10 infused patients to date, four patients sadly died on study, two due to the progression of their leukemia and two due to sepsis (blood poisoning), a common complication of advanced acute lymphoblastic leukemia. None of the patients were admitted to intensive care due to cytokine release syndrome. One patient developed delayed G3 neurotoxicity following high levels of CAR T expansion, which was quickly reversed with steroids. At the one month stage, eight of nine patients then alive (88%) had a molecular complete response. One patient died of sepsis before the one-month evaluation point. More up-to-date information, taken at a range of 0.62 to 10.6 months after infusion, six of ten patients were alive and continue to be in molecular remission. There continues to be evidence of ongoing B cell aplasia and CAR T persistence (in other words, the therapy was still working).
“AUTO1 delivered promising early remission rates, CAR T cell expansion and persistence in this adult acute lymphoblastic leukemia trial cohort,” said Dr. Roddie. “Despite enrolling patients with high tumor burden, the safety profile in the trial appears to compare very favorably to other CD19 CARs and is consistent with the safety profile of AUTO1 observed in pediatric patients in the CARPALL trial.”
“These data from the ALLCAR19 study of AUTO1 in relapsed refractory ALL, while early, are extremely encouraging, with a high response rate we now associate with CAR T cell therapies, but with a potentially improved safety profile. If AUTO1 continues to be associated with a lower incidence of adverse events with additional patients treated, this could represent an important advance for more vulnerable adult patients, as side effects of these therapies, including serious cytokine release syndrome and neurotoxicity, limit our ability to treat these individuals.” said Krishna Komanduri, M.D., Kalish Family Chair in Stem Cell Transplantation and Director, Adult Stem Cell Transplant Program at the Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine.
“The strong persistence of the CAR T cells over time, coupled with the low frequency of severe CRS events seen in these patients, represent encouraging initial data for AUTO1 in relapsed/refractory adult ALL,” said Dr. Christian Itin, chairman and chief executive officer of Autolus Therapeutics. “We expect AUTO1 in adult ALL to move into a registration trial towards the end of this year.”
SYNC / WPCT : Syncona/Woodford investment Autolus reports positive data