An international Phase 2 trial testing the investigational CAR T-cell therapy bb2121 for the treatment of relapsed or refractory multiple myeloma patients has completed patient recruitment, Celgene and bluebird bio announced.
The KarMMa trial (NCT03361748) included 140 patients across the U.S., Canada, and Europe, who had received at least three prior myeloma therapies — including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody — and failed to respond to their last treatment.
“We are committed to developing new treatment options to improve the care of patients with multiple myeloma, and completing enrollment of the KarMMa study moves us closer to this goal,” David Davidson, MD, chief medical officer at bluebird bio, said in a press release.
“As we advance our clinical studies of bb2121 in earlier lines of therapy in collaboration with our partners at Celgene, we remain very grateful to the patients, families and healthcare providers who have made this program possible,” Davidson added.
The treatment uses patients’ own T-cells — a type of immune cell — and genetically modifies them in the laboratory to recognize a protein called B-cell maturation antigen (BCMA), which is present on the surface of multiple myeloma cells. Once injected back into the patient’s bloodstream, the T-cells are primed to bind and kill all tumor cells producing the BCMA factor.
KarMMa is an open label, single-arm study aiming to evaluate the efficacy and safety of bb2121 in patients with hard-to-treat multiple myeloma.
Participants will receive escalating doses of bb2121 — ranging from 150 million to 450 million cells — to determine the safest and most effective dose. The therapy will be administered following a chemotherapy regimen to deplete white blood cells, which makes room for the CAR T-cells while eliminating immune cells that may threaten CAR T-cell expansion.
The trial’s main objective is to determine the amount of patients who respond to the treatment two years after the infusion. Secondary objectives include complete response rate, the length of time a patient lives without their disease worsening, and overall survival, among other parameters.
Earlier this year, Celgene presented data from a Phase 1 trial showing that 94% of advanced multiple myeloma patients who received doses of 150 million cells or higher responded to the treatment, including 56% with complete tumor eradication seen on imaging scans.
Moreover, six months after entering the trial, 81% of patients were still alive and 71% showed no signs of disease worsening. The Phase 1 results also showed that bb2121 was safe with no severe toxicity affecting the nervous system.
“We continue to be excited about bb2121 as a potential first-in-class BCMA-targeted therapy for patients with multiple myeloma,” said Alise Reicin, MD, president of global clinical development for Celgene.
“We would like to thank everyone who enabled this achievement, especially the patients and caregivers, and we congratulate the physicians and others involved in the KarMMa study, including our dedicated partners at bluebird bio. We look forward to seeing the data from this study and are progressing our broader bb2121 development program as we advance closer toward delivering this important new option to appropriate patients in need,” Reicin added.
The U.S. Food and Drug Administration granted bb2121 breakthrough therapy status for relapsed or refractory multiple myeloma in November 2017. It also received a priority medicines (PRIME) designation from the European Medicines Agency.