VIENNA, Austria and BERKELEY, Calif.—Aduro Biotech, Inc. today announced the presentation of updated, interim safety and efficacy data from an ongoing Phase 1b clinical trial of its novel immunotherapy, CRS-207, in combination with standard of care chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). Of the 34 evaluable patients, disease control was observed in 94 percent (32/34), including 59 percent (20/34) with partial responses and 35 percent (12/34) experiencing stable disease following treatment with CRS-207 and chemotherapy. Of note, in three patients who had tumor biopsies completed, biomarker analysis data available at the time of the presentation showed in all three patients a consistent and marked recruitment of immune cells, including CD8+ T cells, dendritic cells and natural killer cells, following treatment with CRS-207.
The results were presented by Raffit Hassan, M.D., co-chief of the Thoracic and GI Oncology Branch at the National Cancer Institute, in a spotlight poster presentation (abstract #515/P249) at the 40th European Society for Medical Oncology (ESMO)/18th European Cancer Congress (ECC) held September 25-29, 2015 in Vienna, Austria.
"The data in this trial continue to be impressive in the front-line treatment of mesothelioma," said Dr. Hassan. "We are encouraged by the high disease control rate in patients treated with this combination and will continue to evaluate and track the durability of the responses, which are ongoing."
Dirk G. Brockstedt, Ph.D., senior vice president of research and development at Aduro added, "Our new immunohistochemistry biomarker data is interesting as it supports our hypothesis that the tumor microenvironment is altered by our immunotherapy. These data show an increase of tumor-attacking immune cells recruited and deployed where they are needed most. We look forward to presenting final results from this trial with additional biomarker data in 2016. As previously announced, based on the compelling data thus far, we plan to advance the combination regimen with CRS-207 and chemotherapy into a pivotal Phase 3 clinical trial in the front-line setting."
At the time of the ESMO presentation, the multi-center Phase 1b study had completed enrollment with 38 patients who were chemotherapy-naive, with unresectable MPM, good performance status (ECOG 0 or 1) and adequate organ function. Under the trial design, eligible patients received two treatments with CRS-207 two weeks apart, followed by up to six cycles of standard of care pemetrexed and cisplatin chemotherapy three weeks apart and two CRS-207 treatments three weeks apart. Clinically stable patients receive CRS-207 maintenance courses every eight weeks and are followed until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.
Median duration of response was 5.3 months (95 percent CI: 4.7 - 16.7 months) and median progression free survival was 8.5 months (95 percent CI: 6.9 - 10.8 months). No treatment-related serious adverse events or unexpected toxicities were observed. Treatment, follow-up and immune response evaluations are ongoing.
Mesothelioma is a form of cancer that affects the smooth layer of mesothelial cells that surround the chest, lungs, heart and abdomen. Malignant pleural mesothelioma (MPM), which affects the thin balloon-shaped lining of the lungs, is the most common form of this disease and accounts for approximately 3,000 cases a year in the U.S. MPM is an aggressive disease with a poor prognosis. Most MPM patients are not candidates for surgical resection. Based on prior studies, expected median time to progression is 5.7 months and median overall survival is 12.1 months with combination pemetrexed and cisplatin chemotherapy. The tumor-associated antigen mesothelin is overexpressed on the majority of mesothelioma tumors.
CRS-207 is one of a family of product candidates based on Aduro's live-attenuated, double-deleted (LADD) Listeria monocytogenes immunotherapy platform that induces a potent innate and T cell-mediated adaptive immune response. 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, endometrial and gastric cancers.
Aduro Biotech, Inc. is a clinical-stage immunotherapy company focused on the discovery, development and commercialization of therapies that transform the treatment of challenging diseases. Aduro's technology platforms, which are designed to harness the body's natural immune system, are being investigated in cancer indications and have the potential to expand into autoimmune and infectious diseases. Aduro's LADD technology platform is based on proprietary attenuated strains of Listeria that have been engineered to express tumor-associated antigens to induce specific and targeted immune responses. Based on compelling clinical data in advanced cancers, this platform is being developed as a treatment for multiple indications, including pancreatic, lung and prostate cancers, mesothelioma and glioblastoma. Aduro's cyclic dinucleotide platform is designed to activate the intracellular STING receptor, resulting in a potent tumor-specific immune response. Aduro is collaborating with leading global pharmaceutical companies to expand its products and technology platforms.