NeoStem launches pivotal Phase 3 melanoma immunotherapy study

NEW YORK—NeoStem, Inc., a biopharmaceutical company developing novel cell-based individualized medicine therapies, has announced the randomization of the first patient in the Intus Phase 3 clinical trial investigating the efficacy of the company's patient-specific targeted cancer immunotherapy candidate NBS20 (USAN = 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 U.S. Food and Drug Administration (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 NBS20 therapeutic vaccine. 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 percent compared to 31 percent for control patients (p=0.007), which was consistent with the previous Phase 2 trial's findings in which NBS20 demonstrated 73 percent 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 (a protein secreted by immune cells that helps stimulate other immune cells to promote immune defenses against disease).

"The randomization of the first patient in the pivotal Phase 3 trial for NBS20 represents the achievement of a significant milestone for NeoStem, marking our transformation into a Phase 3 immuno-oncology company. We are now part of a select group of immunotherapy companies at such an advanced clinical development stage," said Dr. David J. Mazzo, NeoStem CEO.

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 (U.S., 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.

"We are pleased to take another step in our efforts to demonstrate the efficacy of this patient-specific therapy in the hope of improving long-term survival of patients with metastatic melanoma, especially given approval of recent therapies that have yielded strong response rates without demonstrating substantial impact on survival," said Dr. Robert Dillman, vice president, oncology of NeoStem and founder of the NBS20 technology.

In addition to metastatic melanoma, the platform technology on which NBS20 is based is potentially applicable across multiple solid tumor types, including advanced lung, colon, kidney, ovarian and hepatocellular carcinomas, and glioblastoma multiforme—indications that collectively lead to more than 200,000 deaths in the United States each year.

Melanoma, which originates in pigment-producing cells known as melanocytes, is the most lethal form of skin cancer. Melanoma is often caused by unrepaired DNA damage to skin cells from UV radiation. Patients who have progressed to stage IV melanoma have a cancer that has metastasized to distant sites in the body such as the lymph nodes, lungs, liver or brain. As a result, advanced melanoma is exceedingly difficult to treat, with a five-year survival rate of approximately 15 percent. There are 20,000 estimated new cases of metastatic melanoma, and an estimated 10,000 deaths from metastatic melanoma, each year in the United States.

Treatments for stage IV melanoma are typically directed at slowing the growth of the cancer and prolonging survival. Current treatment options include radiation, chemotherapy, surgical resection, immunotherapy, or a combination approach. Unfortunately, current therapies have had limited impact on long-term survival for most patients. Even with the newer targeted therapies (anti-checkpoint inhibitors and specific enzyme inhibitors), half of patients with metastatic melanoma still die within 13 to 17 months from the start of such treatment. Administering certain anti-melanoma drugs at higher doses or in combinations may be more effective, but often results in more severe side effects.

NeoStem is a biopharmaceutical company pursuing the preservation and enhancement of human health globally through the development of novel cell-based individualized medicine therapeutics that prevent, treat or cure disease. The company is developing therapies based on three platform technologies (immuno-oncology, ischemic repair and immunomodulation) with a lead, late-stage clinical program for each. The combination of a rich therapeutics pipeline and an externally recognized in-house center for cell therapy process development and manufacturing has created an organization which purports to have unique capabilities for accelerated and efficient product development.