On March 25, 2015 Cellular Biomedicine Group reported clinical data from its CAR-T immuno-oncology clinical development programs (Press release, Cellular Biomedicine Group, MAR 25, 2015, View Source [SID:1234502522]). The data will be discussed by Dr. Wei (William) Cao, PhD, BM, Chief Executive Officer of Cellular Biomedicine Group, at the 2015 Annual Regen Med Investor Day on March 25 in New York City .

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Dr. Cao commented, "We are very pleased with the efficacy and toxicity profile of our CAR-T technology, given the advanced stage of the cancer patients in the trials. With over 3.5 million new cancer patients diagnosed every year in China, developing safer and more effective cancer immunotherapy programs with leading hospitals will serve urgent unmet medical needs. We look forward to additional progress in advancing our CAR-T cell pipeline with further clinical development of our CD19, CD20, CD30 and EGFR-HER1 constructs."

About the Trials

The CAR-T trials were designed and conducted by Chinese PLA General Hospital ("PLAGH", Beijing, also known as "301 Hospital"), led by Principal Investigator Wei Dong Han, MD, PhD, head of PLAGH’s cancer immunotherapy department. They studied genetically engineered lymphocyte therapy in treating patients with B-cell leukemia or lymphoma that is relapsed (after stem cell transplantation or intensive chemotherapy) or refractory to available therapeutics. The studies recruited male and female subjects with CD19+ and CD20+ B cell malignancies with no available curative treatment options (such as autologous or allogeneic SCT) that had limited prognosis (several months to < 2 year survival) with currently available therapies.

CAR-T CD19 for Acute Lymphocytic Leukemia (B-cell ALL) Data Analysis

Nine adult patients with relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-cell ALL) were enrolled in this CAR-CD19 T cell therapy trial. Results showed a complete response (CR) rate of 22.2% (two out of nine patients) and a partial response (PR) rate of 44.4% (four out of nine patients) for an overall response rate (ORR) of 66.7% (six out of nine patients). Further subgroup analysis showed an overall response rate (ORR) of 71.5% (five out of seven patients) in the six CD19 patients with extramedullary involvement and one patient with no extramedullary lesions and treated with autologous CAR-CD19 T cell therapy. In the six CD19 patients with extramedullary leukemia involvement or bulky adenopathy, an overall response rate (ORR) of 66.7% (four out of six patients) was achieved. Two of the nine patients with extramedullary lesions received allogeneic CAR-CD19 T cell therapy (CBM-C19.a1) and had converted mixed to complete donor chimerism at the onset of graft-versus-host disease (GVHD). One of those patients eventually died of GVHD, but the other gradually reached a complete hematologic remission and a partial regression of her extramedullary leukemic lesions. There were two Grade 2-3 toxicities and GVHD Grade 4 toxicities.

This study is registered at www.clinicaltrials.gov as NCT01864889.

CAR-T CD20 for Advanced Diffuse Large B Cell Lymphoma (DLBCL) Data Analysis

The Company also summarized the results of a Phase I clinical trial on CAR-CD20 T cell therapy (CBM-C20.1), which enrolled seven patients with chemotherapy refractory advanced diffuse large B cell lymphomas (DLBCL). One of the two patients with no bulky tumors achieved a 14-month durable and ongoing complete remission by cell infusion only, and another achieved a 6-month tumor regression achieving a complete response (CR) rate of 50% (one out of two patients) and an overall response rate (ORR) of 100% (two out of two patients). Of those patients with bulky tumor burden, four of five patients were evaluable for clinical efficacy. Of those four patients, three achieved three to six month tumor regression for an overall response rate (ORR) of 75% (three out of four patients).

Delayed toxicities related to CAR-CD20 cell infusion are directly correlated to tumor burden, and mainly included, but were not limited to, curable cytokine release symptoms and tumor lysis symptoms, and these results were achieved by combining debulking conditioning regimens in advanced DLBCL patients with bulky tumors. Overall there were three Grade 2-3 toxicities and one Grade 4 toxicity.

This study is registered at www.clinicaltrials.gov as NCT01735604. Publication source: Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.

Further details of the clinical data may be viewed in the Company’s most recent presentation filed on Form 8k with the SEC, which can be found on the Company’s website at the following link, View Source under SEC filings or presentations.

The Company expects to release Phase I clinical data in the third quarter of 2015 from its clinical studies of the CAR-T constructs targeting CD30-positive Hodgkin’s lymphoma and EGFR-HER1-positive advanced lung cancer.

On March 25, 2015 BioLineRx reported successful top-line results from the Phase 1 safety and efficacy study of its lead clinical candidate, BL-8040, as a novel approach for mobilization and collection of bone-marrow stem cells from the peripheral blood circulation (Press release, BioLineRx, MAR 25, 2015, View Source [SID:1234502521]). All safety and efficacy endpoints were met, showing that treatment with BL-8040 as a single agent was safe and well tolerated at all doses and resulted in efficient stem cell mobilization and collection in all study participants. Importantly, the results support BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care.

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Robust stem cell mobilization was evident in all treated participants, across the different doses tested, supporting a novel approach to stem cell collection. After a single administration, BL-8040 enabled collection of a yield of stem cells that exceeds the number required to support a transplant in all treated participants, following only one collection procedure. The Company intends to present the full set of study results at the European Hematology Association (EHA) (Free EHA Whitepaper) Conference taking place in Vienna in June 2015.

Dr. John DiPersio, Chief of the Division of Oncology at Washington University School of Medicine in St. Louis, stated, "I am very impressed and encouraged by the activity of BL-8040 in promoting stem cell mobilization and collection as a single agent. The robust effect seen in all participants substantially differentiates this compound from the currently approved mobilization regimens, which require four to five days of treatment and one to three full-day apheresis sessions, and can be associated with side effects including bone pain. Therefore, a novel agent with the capacity to rapidly mobilize substantial amounts of stem cells, while providing a shorter and better tolerated drug administration and cell collection regimen, will be of great value both medically and in terms of patient comfort."

"We are very enthusiastic about the study results showing the outstanding activity of BL-8040 in promoting stem cell mobilization. The results exceeded our expectations, and validate BL-8040 as a highly differentiated stand-alone treatment for stem-cell collection. We plan to meet with the FDA as soon as practicable, in order to discuss the results of this study and obtain more clarity on the next steps in the clinical development program for this indication," commented Dr. Kinneret Savitsky, CEO of BioLineRx. "In addition to stem-cell mobilization, our BL-8040 platform is also undergoing a Phase 2 study for treating relapsed and refractory acute myeloid leukemia patients, results of which are expected in the second half of 2015. In addition, as recently reported, we expect to commence clinical trials for three additional indications for BL-8040 in the second quarter of 2015."

The Phase 1 safety and efficacy study consisted of two parts. The first part was a randomized, double-blind, placebo-controlled, dose escalation study exploring the safety and tolerability of escalating repeated doses of BL-8040 in three cohorts of eight healthy volunteers. Based on data from the first part, an optimal safe and efficacious dose of BL-8040 was selected, which was used as a stand-alone therapy in a single cohort of eight healthy volunteers in the second open-label part of the study. This part of the study was designed to assess BL-8040’s stem cell mobilization capacity, as well as the yield of cells collected by apheresis. Secondary efficacy endpoints of the study included the pharmacodynamic and pharmacokinetic profile of the drug, as well as an evaluation of the viability and biological activity of cells mobilized by BL-8040 and collected by apheresis.