Date: 2016-01-06
Type of information: discontinuation of development
phase: 3
Announcement: discontinuation of development
Company: NeoStem (USA - NY)
Product: NBS20 -CLBS20 - (eltrapuldencel-T)
Action
mechanism: cell therapy/cell immunotherapy. NBS20 is an autologous initiating cell immune based therapy intended to eliminate the tumor cells capable of causing disease recurrence. NeoStem’s immunotherapeutic approach uses the patient’s isolated and purified tumor stem cells to train the immune system (Killer T-cells, CD8+) to identify and eliminate cancer stem cells, the root cause of tumor formation and the key drivers of tumor escape, tumor genesis, self-renewal and recurrence of cancer.
Disease: stage III recurrent or stage IV metastatic melanoma
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: The Intus study is a multi-national, randomized, double-blind, placebo-controlled Phase 3 clinical trial in which stage III recurrent or stage IV metastatic melanoma patients will be randomized in a 2:1 ratio to receive either NBS20 (autologous dendritic cells loaded with antigen from self-renewing, proliferating autologous tumor cells in GM-CSF) or a control treatment (peripheral blood mononuclear cells obtained from apheresis product in GM-CSF). The study is expected to randomize 250 eligible patients across approximately 50 sites internationally (US, Canada, Australia, New Zealand and, potentially, select countries of the EU); each patient will receive subcutaneous injections once weekly for three consecutive weeks, and then once monthly for five months. (NCT01875653)
Latest
news: * On January 6, 2016, Caladrius Biosciences announced an increased focus of its strategic priorities and provides 2016 revenue guidance based on growth at its PCT subsidiary. Following a comprehensive review of the Company’s existing operations and development pipeline, as well as an updated assessment of current market dynamics, current and expected future competitive therapies and the Company’s financial resources, Caladrius has decided to shift greater focus and resources to its growing cell therapy process development, optimization and manufacturing services business at its PCT subsidiary. The rapidly developing cell therapy industry, with several cell-based therapies approaching market approvals which are expected to generate additional demand for commercial manufacturing infrastructure, along with PCT’s continued trend of strong revenue growth, supports the Company’s commitment to focus on growth opportunities for PCT. Caladrius Biosciences has also reconfirmed its commitment to pursue further development of its immune modulation platform, with a Phase 2 proof-of-concept clinical trial for a T regulatory cell therapy in type 1 diabetes as the primary focus, while choosing to discontinue the current Phase 3 study of CLBS20 as monotherapy for metastatic melanoma. * On November 9, 2015, Caladrius Biosciences announced that the Company presented two posters including new clinical and analytical data at the Society for Immunotherapy of Cancer (SITC) 2015 Annual Meeting, which took place from November 4-8 in Baltimore, Maryland. The data, drawn from ongoing analysis and follow-up from a completed Phase 2 study, further support the technology being explored in a currently enrolling Phase 3 clinical trial to investigate Caladrius’ lead product candidate, CLBS20, for the treatment of metastatic melanoma. Data highlights included: A new subset analysis of patient results from a 42-patient, open-label, randomized Phase 2 trial that compared the treatment effects of CLBS20 (n=18) versus a control group of irradiated tumor cells alone (n=24). The analysis concluded that CLBS20 immunotherapy was associated with improved survival in each of the four different subsets defined by the stratification variables (namely measurable or non-measurable disease as defined by RECIST and most advanced stage of disease being stage IV or recurrent stage III – see below for associated table). * On April 29, 2015, NeoStem, a biopharmaceutical company developing novel cell-based individualized medicine therapies, announced the randomization of the first patient in the Intus Phase 3 clinical trial investigating the efficacy of the patient-specific targeted cancer immunotherapy candidate NBS20 (eltrapuldencel-T) in patients with stage III recurrent or stage IV metastatic melanoma. The Intus trial has been granted a Special Protocol Assessment (SPA) by the FDA, which permits this trial, if successful, to be the sole pivotal trial necessary for registration. The NBS20 development program has also been granted Orphan Drug and Fast Track designations by the FDA. The Intus trial is based on consistent, compelling results from two Phase 2 trials in identical patient populations evaluating the therapeutic vaccine that has become NBS20. The more recent of the two trials was a randomized trial comparing NBS20 to injections of autologous irradiated (inactivated) tumor cells in 42 patients. At two years, survival was 72% compared to 31% for control patients (p=0.007), which was consistent with the previous Phase 2 trial's findings in which NBS20 demonstrated 73% two-year survival in 54 patients, with a median survival of five years. Toxicity was minimal and consisted of mild to moderate local injection site reactions of the type normally associated with injections of GM-CSF.
David J. Mazzo, Ph.D., Chief Executive Officer of Caladrius said, “The treatment paradigm in metastatic melanoma was transformed during the course of 2015 by the accelerating adoption of multiple immune checkpoint inhibitors used as monotherapy and in combination treatments. These new drugs have significantly improved outcomes in metastatic melanoma and therefore have altered the opportunity for a monotherapy such as CLBS20 in a landscape that is quickly converting to combination therapies. Therefore, we have concluded that, as designed, our current program in metastatic melanoma will not optimally leverage this asset and we will therefore discontinue the ongoing Phase 3 clinical study with CLBS20 as a monotherapy for the treatment of recurrent Stage III or Stage IV metastatic melanoma. As a result, we will reduce associated staff by approximately 40 employees at our Irvine, California facility. That said, we continue to believe in the potential of CLBS20 as a life-prolonging immunotherapeutic and will pursue licensing or partnership opportunities for its continued development as part of a combination therapy and in different oncology indications. The emphasis will be on collaborating with a company that will allow us to exploit the novel antigen presentation and T cell activation approach of CLBS20.”
A series of studies undertaken by the company to elucidate mechanism of action and support expectation of efficacy for CLBS20 in which the data supported the tumor-initiating properties and the antigenic potential of the self-renewing cancer-initiating cells that Caladrius isolates in its manufacturing process. The data also indicate a statistically significant relationship between immune response triggered by CLBS20 and overall survival of melanoma patients. The analysis showed decreases in multiple tumor and inflammation markers at four weeks after baseline in responding patients treated with CLBS20.
