Celgene says it has raised the top dose and expanded its trial of its anti-BCMA CAR-T candidate for myeloma licensed from Bluebird Bio, but the company still thinks it’s on course for approval in 2020.
The study in question is KarMMa, a phase 2 trial in relapsed and refractory myeloma patients previously treated with at least three earlier therapies that will be used to support regulatory filings expected in 2019.
The change means the upper dose of bb2121 on test has been raised to 450 million CAR+ T cells, while the number of subjects has also been increased to 140 from an earlier target of 94. The prior dose range under test was 150 to 300 million cells.
The decision also affects a phase 1, extended follow-up study of the CAR-T called CRB-401, with the top dose of the anti-B-cell maturation antigen (BCMA) therapy raised to the same level and the number of participants hiked by up to 20 patients over its initial cohort of 46.
“This change in dosing is based on the totality of the clinical data for the bb2121 product candidate to date,” says Bluebird in a Securities & Exchange Commission (SEC) filing. Celgene shares rights to bb2121 in the U.S. and has sole responsibility for the CAR-T elsewhere under the terms of a deal with Bluebird agreed in March.
Neither company has said anything further about the decision, but the changes are clearly designed to increase the chances of a positive outcome. For now, it’s not clear whether it was felt that the dose needed to increase to improve efficacy, for example, or if encouraging safety data has allowed a more aggressive approach to try to push clinical responses as high as possible.
Celgene tells us in a statement that "a
Celgene tells us in a statement that "as the 8k states, the decision was made based on the totality of the data so far. In the earlier studies, we have seen a dose-related response, so we have added a higher dose to the study and will enroll additional patients. Consistent with our previous timing, we expect a first approval for bb2121 in 2020."
Early-stage clinical results reported at this year’s American Society of Clinical Oncology (ASCO) have built excitement about bb2121, with a cohort of 18 patients on the 150 to 300 million-dose range recording a median progression-free survival (PFS) of just under 12 months and 50% complete response rate. That trial was also expanded from 21 to 43 patients midway through.
Crucially, there seemed to be no difference in the response depending on the level of tumor BCMA expression—which could mean there is no need to test patients for BCMA status before therapy.
Shares in Celgene and Bluebird barely shifted in the wake of the SEC filing, suggesting investors are fairly relaxed about the protocol change.
Meanwhile, Celgene and Bluebird are forging ahead with bb2121 in earlier stages of myeloma, initially with a trial in third-line myeloma comparing the CAR-T to a triple regimen of Genmab and Janssen’s Darzalex, Celgene’s Pomalyst and dexamethasone.