Poseida Therapeutics said that 21 of 23 patients (91%) responded to the allogeneic CAR-T therapy it’s developing with Roche when given a higher dose of a chemo drug called cyclophosphamide than is typical.
In addition, five of the 23 patients achieved a complete response, or stringent complete response, after receiving P-BCMA-ALLO1 and the higher chemo dose, the company said Friday.
Separately, Poseida disclosed Friday in an SEC filing that Roche did not pick up an option for another CAR-T program targeting both BCMA and CD19. Poseida’s shares $PSTX ticked down in Monday morning trading, dipping about 3%.
The updates follow Poseida’s presentation at the American Society of Hematology’s annual meeting last December. The company said then that data were “highly dependent” on patients’ cyclophosphamide regimens. Patients who took lower levels of cyclophosphamide before receiving P-BCMA-ALLO1 infusions did not respond to the CAR-T. Those results were recorded after just four weeks, raising questions about the durability of the therapy.
The newest results come from a trial arm that Poseida said has an “optimized” level of cyclophosphamide at 750 mg/m2, allowing the chemo to clear out enough space in patients’ bone marrow for the CAR-T to have an effect. Median follow-up was 3.5 months, according to Poseida. Cyclophosphamide is typically given at 300 mg/m2, though it can be given in higher doses in conjunction with CAR-T.
Increasing cyclophosphamide doses across trial arms appear correlated with “increased CAR-T cell expansion and persistence,” according to a note that William Blair analyst Sami Corwin wrote to investors on Friday. She added that the 91% overall response rate was higher compared to the pooled ORR of 54% from all cohorts.
Corwin also suggested P-BCMA-ALLO1 could have a benefit regardless if patients previously received BCMA-targeting therapies, pointing out that all nine BCMA-naïve individuals achieved a response. There were also two patients in the 750 mg/m2 cohort who were retreated with the CAR-T at the discretion of their physicians.
Poseida and Roche will move forward with the 750 mg/m2 cyclophosphamide regimen in a Phase 1b expansion study that is expected to begin “shortly,” Poseida execs said Saturday on an investor call. Poseida will receive an undisclosed milestone payment for launching the trial.
ASH follow-up
On top of the new cohort data, Poseida also provided updates from earlier cohorts testing other levels of cyclophosphamide.
In the lowest cyclophosphamide regimen of 300 mg/m2, five of 24 patients (21%) responded, though there were no complete responses. That’s up from zero out of eight responses as reported at ASH. (Patients in this cohort received varying doses of CAR-T.) In the middle cyclophosphamide regimen of 500 mg/m2, eight of 19 (42%) individuals responded, compared to four out of five (80%) at ASH.
And in the highest cyclophosphamide regimen of 1,000 mg/m2, seven of 10 patients responded (70%) compared to five of six (83%) at ASH. There were two complete responses (20%) in this cohort, which was unchanged from the data presented at ASH.
Poseida also looked at the median duration of response for patients in the middle and high chemo regimens who are at least six months past treatment. (Poseida did not say how many patients this encompassed.) Among these patients, the median duration of response was 232 days, or 7.6 months.
Two physicians who spoke on Poseida’s call — Vanderbilt University’s Bhagirathbhai Dholaria and UCSF’s Thomas Martin — said they believed that result was impressive due to the heavily pretreated nature of the patient population.