Celgene and partner bluebird bio announced Monday updated results from a Phase I study showing that all 15 evaluable patients with relapsed/refractory multiple myeloma who received an active dose of the anti-B-cell maturation antigen (BCMA) CAR-T therapy bb2121 achieved an objective response. Michael Pehl, president of haematology and oncology at Celgene, remarked "the heavily pretreated, relapsed/refractory patients in this study have few effective treatment options, highlighting the importance of this interim data," adding that patients in the trial received a median of seven lines of prior therapy.
In the study, the results of which are being presented at the ASCO annual meeting, 21 heavily pre-treated patients with relapsed/refractory multiple myeloma were assigned to treatment with one of four dose cohorts, including three active doses. Eighteen patients who had completed their initial multiple myeloma tumour restaging were evaluable for efficacy, including 15 people assigned to the three active treatment arms, while all 21 patients were evaluable for safety.
As part of the treatment, patients were administered a conditioning regimen of cyclophosphamide and fludarabine followed by a bb2121 infusion. The primary endpoint of the study was the incidence of adverse events (AEs) and abnormal laboratory test results, including dose-limiting toxicities, while secondary study goals covered disease-specific response criteria such as complete response, very good partial response and partial response.
Celgene and bluebird bio said that among patients assigned to active treatment, 27 percent achieved complete responses, while 47 percent achieved a very good partial response, with the remainder in a partial response. Results showed that one of the patients who had a complete response degraded to a very good partial response near 48 weeks. Bluebird bio spokesperson Manisha Pai commented "this is not a clinical relapse or progression. It is a phenomenon that has been seen with other therapies."
The companies added that all four patients tested for minimal residual disease tested negative, and no cases of disease progression had occurred in the active cohorts at the time of data cut-off on May 4. Regarding safety, Celgene and bluebird bio indicated that no dose-limiting toxicities have been observed among patients in the study. Meanwhile, the most common Grade 3 or 4 AEs were cytopaenias commonly associated with cyclophosphamide and fludarabine lymphodepletion, hyponatraemia, cytokine release syndrome in two patients, upper respiratory infection and syncope.
David Davidson, bluebird bio's chief medical officer, said "although these data are still early, it is encouraging that no patient in the active dose cohorts has had myeloma progression," continuing "in light of these results, we look forward to initiating the expansion phase of the CRB-401 study in the coming months."
Commenting on the findings, Leerink analyst Michael Schmidt stated "the efficacy and safety profile of bb2121 continues to look very strong." Schmidt added "we believe these data position [bluebird bio and Celgene] well among companies developing CAR-T products in multiple myeloma and provide additional validation for bb2121 and [bluebird bio's] emerging CAR-T platform."
Celgene and bluebird bio entered into an agreement in 2013 to jointly develop CAR-T therapies to target and destroy cancer cells. The partnership was amended in 2015 to focus on the development of product candidates targeting BCMA, with bluebird bio regaining rights to CAR-T products outside BCMA.
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