On Jun 5, 2017 bluebird bio, Inc. (NASDAQ:BLUE), and Celgene Corporation (NASDAQ:CELG) reported that updated results from the ongoing CRB-401 Phase 1 clinical study of bb2121, an investigational anti-BCMA CAR T cell therapy, in 18 patients with relapsed/refractory multiple myeloma will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois (Press release, bluebird bio, JUN 5, 2017, View Source [SID1234519361]). The objective of this Phase 1 dose-escalation study is to evaluate safety and efficacy of bb2121 and determine a recommended Phase 2 dose. bluebird bio and Celgene are jointly developing bb2121.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"It is impressive to see objective responses in all patients treated at dose levels of 150 x 106 CAR+ T cells or higher in such a heavily pretreated population, including those with high tumor burden. We are encouraged by the duration and depth of responses, and pleased that the safety profile remains readily manageable," said David Davidson, M.D., chief medical officer, bluebird bio. "Although these data are still early, it is encouraging that no patient in the active dose cohorts has had myeloma progression. In light of these results, we look forward to initiating the expansion phase of the CRB-401 study in the coming months."

"The heavily pretreated, relapsed/refractory patients in this study have few effective treatment options, highlighting the importance of this interim data. All patients previously underwent autologous HSCT, and received a median of 7 lines of prior therapy," said Michael Pehl, President, Hematology and Oncology for Celgene. "The consistency, depth and durability of these patients’ responses coupled with a manageable safety profile is very exciting, and we believe will provide hope for patients in this setting. Efforts are underway to advance the development of bb2121 for patients with relapsed/refractory multiple myeloma."

First-in-Human Multicenter Study of bb2121 anti-BCMA CAR T Cell Therapy for Relapsed/Refractory Multiple Myeloma: Updated Results. (Abstract #3010)

Presenter: Jesus G. Berdeja, M.D., Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN

Date: Monday, June 5, 2017, 4:45-6:00 pm CT (poster discussion); 8:00-11:30 am CT

Location: Hall D1

Session Title: Poster Discussion Session: Developmental Therapeutics—Immunotherapy

The open-label Phase 1 CRB-401 study (NCT02658929) is investigating the administration of bb2121 anti-BCMA CAR T cells in patients with relapsed and/or refractory multiple myeloma. The primary endpoint of the study is incidence of adverse events (AEs) and abnormal laboratory test results, including dose-limiting toxicities (DLTs). The study also seeks to assess disease-specific response criteria including: complete response (CR), very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma. The study also seeks to determine the recommended dose for further clinical trials.

Patients on study were heavily pre-treated, with a median of seven prior therapies (range: 3 – 14):

100% previously treated with lenalidomide and bortezomib
91% previously treated with pomalidomide and carfilzomib
71% previously treated with daratumumab
29% of patients were penta-refractory (bortezomib, lenalidomide, carfilzomib, pomalidomide, daratumumab)
All patients had at least one prior autologous stem cell transplant (ASCT)
As of the May 4, 2017 data cut-off, 21 patients had been enrolled and dosed in four dose cohorts: 50 x 106, 150 x 106, 450 x 106 and 800 x 106 CAR+ T cells. All 21 dosed patients were evaluable for safety, and 18 patients have undergone their first multiple myeloma tumor restaging and were evaluable for efficacy. This study has enrolled patients at seven sites in the U.S., with an anticipated total enrollment of up to 50 patients.

Patients received a conditioning regimen of cyclophosphamide and fludarabine, followed by an infusion of bb2121 anti-BCMA CAR T cells. The CAR T cells were produced from each patient’s own blood cells, which were modified using a lentiviral vector encoding the anti-BCMA CAR.

bb2121 is an investigational compound that is not approved for any use in any country.

Results, as of May 4, 2017 Data Cut-off:


Cohort 1 2 3 4
CAR+ T Cell Dose 50 x 106 150 x 106 450 x 106 800 x 106
Number of
Patients
Evaluable for
Efficacy

3 4 8 3
Overall Response Rate in Cohort 33% 100% 100% 100%
Best Response PD (1 patient)
SD (1 patient)

PR (1 patient)


CR (2 patients; 1
patient MRD
negative)
VGPR (1 patient
MRD negative)
PR (1 patient)




CR (1 patient*)
VGPR (5
patients; 1 patient MRD
negative)
PR (2 patients;
1 patient MRD
negative)
*Patient died of
unrelated cardio
pulmonary arrest

VGPR (1 patient)
PR (1 patient)

CR (1 patient)


All patients in cohorts 2, 3 and 4 with bone marrow
involvement at baseline had no detectable multiple
myeloma cells in their bone marrow on Day 14 or beyond.
Of four patients evaluable for MRD status, all four were found to be
MRD-negative.



Median Prior
Lines of
Therapy


7 (range: 3-14); all patients had at least one prior autologous stem cell
transplant, as well as prior exposure to a proteasome inhibitor and an
immunomodulatory agent; 71% of patients had previously received
daratumumab or CD38 antibody.

Safety
15/21 (71%) of patients had CRS, mostly Grade 1 & 2; 2 patients with
Grade 3 CRS that resolved within 24 hours. 4 patients received
tocilizumab, 1 (Grade 2 CRS) received steroids. The most common
treatment-emergent Grade 3-4 AEs in 21 infused patients include
cytopenias commonly associated with cy/flu lymphodepletion, as well
as Grade 3 events of hyponatraemia (n=4), cytokine release syndrome
(n=2), upper respiratory infection (n=2), and syncope (n=2).