The following article features coverage from the American Society of Hematology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

An investigational chimeric antigen receptor (CAR) T-cell (CAR-T) therapy product that is manufactured using a unique process showed clinical activity and appeared safe in patients with relapsed/refractory multiple myeloma, even when administered in the outpatient setting.

The results of the phase 1/2 clinical trial ( Identifier: NCT03288493) were presented at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

Directed against B-cell maturation antigen (BCMA) and having an embedded safety switch, the investigational product, called P-BCMA-101, is made using transposons instead of the conventional lentivirus, and is manufactured to have a high proportion of T–stem cell memory (Tscm) cells.

Continue Reading

Transposons “preferentially” produce Tscm cells, which have been correlated with higher clinical efficacy, said study presenter Caitlin Costello, MD, Moores Cancer Center, University of California San Diego, in La Jolla. One benefit of this approach is that it may increase safety because Tscm cells gradually differentiate into effector T cells, Dr Costello explained.

Patients received P-BCMA-101 as a single infusion or a divided dose given over 2 or 3 infusions. Patients also had the option of receiving P-BCMA-101 with a combination of other therapies, and for this approach, a cohort received rituximab before and after P-BCMA-101, a second cohort received lenalidomide before and after P-BCMA-101, and a third cohort received lenalidomide at 3 time points: before apheresis, before lymphodepleting chemotherapy, and after P-BCMA-101 infusion.

The manufacturing process was modified during the trial to use a nanoplasmid instead of a standard plasmid to improve transposition efficiency.

A pooled analysis of all dosing strategies and manufacturing processes showed that only 17% of patients developed cytokine release syndrome and none were grade 3 or worse.  Two patients (4%) had neurotoxicity, both of whom had grade 3 or worse severity.

To date, 16 patients have received all study-related treatments in the outpatient setting, said Dr Costello. “Overall, there appears to be no significant difference in the safety between the 2 manufacturing processes.”

Patients who received P-BCMA-101 manufactured using the nanoplasmid had a 66.7% overall response rate, which was higher than the 50% response rate seen among patients who received P-BCMA-101 manufactured using the standard plasmid.

“A modified manufacturing process may improve expansion and efficacy, showing how the use of nanoplasmid exemplifies continuous innovation in manufacturing,” said Dr Costello.

The trial will move forward with the nanoplasmid manufacturing approach.

Disclosures: Some of the presenters disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the presentation abstract.

Read more of Cancer Therapy Advisor‘s coverage of the ASH 2020 meeting by visiting the conference page.


Costello CL, Cohen AD, Patel KK, et al. Phase 1/2 study of the safety and response of P-BCMA-101 CAR-T cells in patients with relapsed/refractory (r/r) multiple myeloma (MM) (PRIME) with novel therapeutic strategies. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 134.