First Cancer Trial Launched Using CAR T Cells Engineered with a Safety Switch

HOUSTON, March 17, 2014 /PRNewswire/ -- Bellicum Pharmaceuticals, Inc. announced today that the first clinical study is underway of a Chimeric Antigen Receptor (CAR) T Cell therapy that incorporates a safety switch to enable rapid elimination of the administered T cells if they threaten the life or health of the patient. Researchers from the National Cancer Institute (NCI) have begun treating pediatric patients with osteosarcoma and other non-neuroblastoma GD2-expressing solid tumors with a third generation CAR T cell therapy that incorporates Bellicum's unique CaspaCIDe^® safety switch technology.

"CAR T cell therapy has recently shown dramatic results including apparent cures in some of the deadliest of cancers, but the treatment can also cause life-threatening toxicities, and has resulted in some patient deaths. Experts in the field have talked about the critical need for an effective safety mechanism to allow the development of more potent products within this new class of immunotherapy," said Kevin Slawin, M.D., Executive Chairman and Chief Medical Officer of Bellicum Pharmaceuticals. "We're excited to be the first to make this a reality by incorporating our unique safety switch into this third generation CAR T cell therapy, thereby potentially giving these patients, and their families and physicians, an added layer of safety."

Bellicum's CaspaCIDe technology consists of an inducible Caspase-9-based cell safety switch, and the small molecule activator, AP1903. CaspaCIDe is engineered into immunotherapy cells, in this case GD2-targeted third generation CAR T cells, before they are introduced to the patient. In the event of a serious or life threatening toxicity caused by the administered T cells, AP1903 is infused to trigger rapid destruction and elimination of the CaspaCIDe-enabled cells. 

CaspaCIDe technology has already demonstrated the ability to selectively eliminate harmful immune cells, resolving acute Graft versus Host Disease (GvHD) in stem cell transplant patients.¹ Bellicum is currently evaluating its own lead CaspaCIDe-enabled product, BPX-501, together with AP1903, in clinical studies to improve transplant outcomes and reduce or eliminate GvHD following stem cell transplant in multiple indications, populations and transplant modalities. The collaboration with NCI represents Bellicum's initial application of its expertise and technology to the clinical advancement of the CAR T cell field.  

Study Details
The Phase I dose escalation trial, led by Crystal L Mackall MD, Chief, Pediatric Oncology Branch, National Cancer Institute, will enroll up to 36 patients primarily with sarcoma or other non-neuroblastoma GD2-expressing solid tumors deemed incurable with standard therapy.

The trial consists of 4 cohorts of at least 3 patients each with an expanded group of at least 12 patients, including at least 6 with osteosarcoma, receiving the highest dose. Enrolled patients will receive escalating doses of autologous T cells engineered to express a third generation CAR, and the CaspaCIDe safety switch. Patients with a partial response or stable disease may receive a second cycle of cells at the next higher dose level.

Patients experiencing a Grade greater than or equal to 3 toxicity, or a Grade 2 toxicity that is believed to be causing substantial risk to the patient, will receive an infusion of activating agent AP1903 to halt the activity of the CAR T cells. A total of 6 doses of AP1903 may be administered. All patients will be measured for tumor response, and as a primary endpoint of the trial, those receiving the activating agent AP1903 will be evaluated for its effects. 

About CAR T Cell Therapy
CAR T cells are immune cells (T cells) that have been engineered to produce a more targeted and potent attack against cancer. CAR T cells are generally classified based on the number of signal transduction domains. First generation CARs, most commonly consisting of a CD3zeta signaling element that helps mediate killing of cells expressing the targeted molecule, have limited efficacy. By adding a co-stimulatory cytoplasmic signal domain, such as CD28 or 4-1BB, second generation CARs have demonstrated enhanced in vivo tumor killing and persistence accompanied by increased potential for life- threatening on- or off-target toxicity. Third generation CAR T cells, which have two co-stimulatory domains combined with CD3zeta, are believed to be the most potent, and therefore also have the highest risk of potential life-threatening toxicity. With the inclusion of a "safety switch," third-generation CAR T cells can now be more safely evaluated in patients.

About Osteosarcoma and Other Pediatric Solid Tumors
Approximately one-fourth of cancer diagnoses in children are non-CNS solid tumors, representing approximately one-third of all deaths due to childhood cancer. This protocol will target non-neuroblastoma GD2+ pediatric solid tumors, which includes all osteosarcomas and a subset of other pediatric solid tumors. Clinical responses for patients with resectable, non-metastatic osteosarcoma are in the range of 60-70% with surgery plus multi-agent chemotherapy.  For patients who present with metastatic osteosarcoma or who have unresectable disease, outcomes are dismal with <20% survival. Similarly, patients with recurrent osteosarcoma have survival rates of approximately 20-30%, even with resection plus or minus chemotherapy. However, even in patients who are cured of their disease, the late side effects of standard therapies are substantial, leaving many patients with chronic lifelong toxicities related to their cancer therapy. Therefore new therapies are needed to diminish toxicity and improve survival for patients with pediatric solid tumors.

About Bellicum Pharmaceuticals  
Bellicum Pharmaceuticals, Inc. is dedicated to improving the treatment of cancers and other serious, life-threatening diseases with safer and more effective cell therapies. By giving physicians control over cells and immune activity inside the body, the Company's Chemical Induction of Dimerization (CID) technology is designed to improve clinical outcomes while greatly expanding the numbers of patients who are eligible for treatment.

¹ Di Stasi A, Tey SK, Dotti G, et al. Inducible Apoptosis as a Safety Switch for Adoptive Cell Therapy. N Engl J Med 2011;365: 1673-83.

SOURCE Bellicum Pharmaceuticals, Inc.