Phase 3 Product Candidate for Metastatic Melanoma
The incidence of metastatic melanoma is steadily on the rise and is now a major cause of cancer death in the US and in Europe. Metastatic melanoma is usually lethal within 1 to 2 years, with a 5-year survival rate of <15%. The current standard of care of surgical resection, radiotherapy and chemotherapy are associated with trauma and/or toxicity, and do not address cancer recurrence, which make up more than two-thirds of all reported local or regional melanoma diagnoses (~20,000 patients). Hence, there is a critical unmet need for a nontoxic, effective, consolidation therapy for these patients.
Antigen-specific immunotherapy is emerging as a new treatment modality, and dendritic cells are recognized as the most efficient antigen presenting cells, with their high ability for molecular identification and transmission. The best source of antigens may come from a patient’s own (autologous) self-renewing, cancer-initiating cells. Caladrius has the unique ability to isolate these cancer-initiating cells and proliferate them in culture. Thus, Caladrius’ immuno-oncology technology (CLBS20, also NBS20) consists of autologous dendritic cells loaded with irradiated autologous cancer-initiating cells which proliferate in cell culture. The potential of CLBS20 for antigen-specific immunotherapy differentiates itself from available therapeutics through:
- Presenting the entire spectrum of antigens from the patient’s own tumor rather than targeting an insufficient number of specific antigens
- Isolating and re-administering specific cells from the patient’s tumor that are self-renewing, that is, those that can regenerate the cancer and cause metastatic spread against which an immune response is most needed.
- The non-toxic nature compared to other approved therapies.
- Excellent long-term survival rates, even in patients who have had Stage IV disease.
- Survival rates comparable to most active agents even in patients with measurable metastatic disease.
- The therapy’s focus on increasing recognition of tumor associated antigens rather than optimizing existing immune response (by enhancing e.g. IL2, or reducing suppression, e.g. Anti-CTLA4 or anti-PD1 or PDL1).
- Induction and enhancement of long-term anti-tumor immunity that is potentially synergistic with other approved therapies.
CLBS20: Uniquely targets cancer-initiating cells (CICs)
Phase 2: Two Trials; Consistent, Compelling Data
A Phase 2 randomized clinical trial was conducted comparing subcutaneous injections of CLBS20 versus injections of autologous tumor cells in patients with advanced melanoma (recurrent Stage III or Stage IV) (N=42). The trial demonstrated superior survival outcomes at two years—survival was increased to 72% compared to 31% for control patients treated with only their own tumor cells suspended in granulocyte macrophage colony stimulating factor (GM-CSF) (p=0.007). The two-year survival rate of 72% confirmed previous trial’s findings in which dendritic cells loaded with antigens from autologous tumor cells demonstrated a 72% 2-year survival (N=54), with a median survival of five years. The toxicity profile was favorable with no grade IV and only one grade III (allergic reaction to the FDA approved immune stimulant GM-CSF) event. There were no significant toxicities or adverse effects on hematopoietic cells or renal function, liver function, or patient performance status.
CLBS20 Phase 3 Background
Based on these findings from the Phase 2 study, a randomized, double-blind, placebo-controlled Phase 3 trial was designed to confirm the benefit of CLBS20 in patients with recurrent Stage III or Stage IV metastatic melanoma. The Phase 3 trial has been granted special protocol assessment (SPA). Our SPA letter states that our Phase 3 clinical trial is adequately designed to provide the necessary data that, depending on outcome, could support a Biologics License Application (BLA) seeking marketing approval of CLBS20. CLBS20 has received fast-track and Orphan Drug designation by the US FDA as well as Advanced Therapeutic Medicinal Product classification by the European Medicines Agency (EMA). The first patient for this study was randomized in April 2015, and enrollment is targeted for completion by Q4 of 2016. Interim analysis of the data is targeted in Q4 of 2017. For additional details, please visit the trial's listing on clinicaltrial.gov.
Intus Phase 3 Study targeting metastatic melanoma
Randomized (2:1), double blind, placebo controlled trial for Stage III recurrent or Stage IV metastatic melanoma patients
Single trial for registration assuming positive outcome
80% power to detect 37.5% reduction in risk of death
Relation to Standard Therapies
Clinical practice based trial
Planned 250 eligible patients
Approximately 50 sites (U.S., Canada, Australia, New Zealand, considering E.U.)
CLBS20: Autologous DC loaded with antigens from autologous cancer-initiating cells
Autologous peripheral blood monocytes