Clinical Trials

Date: 2016-05-16

Type of information: Results

phase: 2b

Announcement: results

Company: Aduro Biotech (USA - CA)

Product: CRS-207 and GVAX Pancreas

Action mechanism: immunotherapy product/therapeutic vaccine/cell therapy. CRS-207 is one of a family of product candidates based on Aduro's live-attenuated, double-deleted (LADD) Listeria monocytogenes immuno-oncology platform that are designed to induce potent innate and adaptive immune responses. CRS-207 has been engineered to express the tumor-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers. GVAX Pancreas is one of a family of GVAX vaccines derived from human cancer cell lines that are genetically modified to express granulocyte-macrophage colony-stimulating factor (GM-CSF), an immune system-stimulating cytokine. GVAX Pancreas is derived from human pancreatic cancer cell lines and is designed to activate specific T cell immunity to pancreatic cancer antigens, including mesothelin.

Disease: pancreatic cancer

Therapeutic area: Cancer - Oncology - Rare diseases

Country: Canada, USA

Trial details: The ECLIPSE trial (Efficacy of Combination Listeria/GVAX Immunotherapy in the Pancreatic Cancer Setting) enrolled 303 adults with previously-treated metastatic pancreatic cancer in over 20 clinical trial sites in the U.S. and Canada . The open-label randomized, controlled 3-arm trial evaluated the safety, immune response and efficacy of the combination immunotherapy of CRS-207 with GVAX Pancreas (with low-dose cyclophosphamide (CY)) and CRS-207 alone, compared to chemotherapy. The primary endpoint of the trial was overall survival. Secondary endpoints included evaluation of clinical and immune response and safety.(NCT02004262)

Latest news:

• • On May 16, 2016, Aduro Biotech announced that the Phase 2b ECLIPSE trial did not meet the primary endpoint of an improvement in overall survival for patients with pancreatic cancer who had failed at least two prior therapies in the metastatic setting. Median overall survival (MOS) in this third-line and greater setting was 3.8 months for patients treated with the immunotherapy regimen of CRS-207 and GVAX Pancreas, 5.4 months for patients treated with CRS-207 alone and 4.6 months for patients administered chemotherapy. There were no unexpected safety findings with the combination of CRS-207 and GVAX Pancreas or CRS-207 alone, and the immunotherapies were generally well tolerated. Full study findings will be presented at a future scientific congress • On June 29, 2015, Aduro Biotech announced that an independent Data Monitoring Committee (DMC) recommended that the Phase 2b ECLIPSE trial of its novel LADD and GVAX immunotherapies continue as planned without modification based on the successful outcome of a pre-specified futility analysis. The DMC assessment included an evaluation of interim primary efficacy and safety data from over half of the anticipated patient population enrolled in the trial. The randomized, controlled three-arm trial is expected to enroll over 300 patients at 21 clinical trial sites in the United States and Canada to evaluate the safety, immune response and efficacy of the combination immunotherapy of CRS-207 in combination with GVAX Pancreas compared to chemotherapy. The trial also has a treatment arm to evaluate CRS-207 as a monotherapy. The primary endpoint of the trial is overall survival in the primary cohort of patients who have received two or more prior therapies for metastatic disease. A second cohort of patients who have received one prior therapy for metastatic disease is also being evaluated.
• Last year, the FDA granted Breakthrough Therapy designation for Aduro's pancreatic cancer combination treatment consisting of CRS-207 and GVAX Pancreas. According to the FDA, Breakthrough Therapy designation is for a drug candidate that treats a serious or life-threatening condition for which preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint over available therapies. Breakthrough Therapy designation was granted based on results from a Phase 2a clinical trial of patients with metastatic pancreatic cancer treated with CRS-207 and GVAX Pancreas. The multi-center trial, which enrolled 93 patients with metastatic pancreatic cancer, demonstrated a statistically significant survival benefit in patients receiving the combination immuno-oncology regimen of CRS-207 and GVAX Pancreas compared to GVAX Pancreas alone. The results were published in the January 2015 issue of the Journal of Clinical Oncology (JCO).
• Results of the Phase 2a clinical trial published in JCO indicated the median overall survival of Arm A patients receiving the combination regimen of CRS-207 and GVAX Pancreas was 6.1 months compared to 3.9 months for Arm B patients receiving GVAX monotherapy (HR=0.5930, one-sided p=0.0172). One-year survival probability for patients in Arm A was 24 percent compared with 12 percent for patients in Arm B. The trial enrolled advanced-stage metastatic pancreatic cancer patients who previously received or refused prior chemotherapy, with most patients having received two or more prior therapies in the metastatic setting. Patients were randomized in a 2:1 ratio to receive two doses of GVAX Pancreas vaccine followed by four doses of CRS-207 (Arm A) or to receive six doses of GVAX Pancreas vaccine alone (Arm B). Clinically stable patients were allowed to receive additional treatment courses.
• Of the 93 patients enrolled, the most frequent treatment-related Grade 3 or 4 adverse event (AE) was asymptomatic, transient lymphopenia, with three patients experiencing Grade 3 lymphopenia and two patients experiencing Grade 4 lymphopenia. There were no other Grade 4 AEs, and there were no other Grade 3 AEs with frequencies higher than five percent in either arm. The most common Grade 3 AEs were transient lymphopenia, fevers, elevated liver enzymes and fatigue.

Is general: Yes