Aduro BioTech, Inc., a clinical stage biotechnology company, today announced the presentation of safety and efficacy data from a Phase 1b clinical trial of its novel immunotherapy CRS-207 in combination with standard chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM). Of the 16 evaluable patients, 69% (11/16) had confirmed durable partial responses (PR) with 25% (4/16) experiencing stable disease (SD) after CRS-207 and chemotherapy. 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 poster presentation at the 2014 American Society of Clinical Oncology Meeting (ASCO) held in Chicago.
CRS-207, based on Aduro's live-attenuated, double-deleted (LADD) Listeria monocytogenes immunotherapy platform, has been engineered to induce a potent innate immune response as well as an adaptive immune response targeting mesothelin, an antigen over-expressed in MPM tumors.
"These results are particularly exciting and encouraging in this difficult-to-treat patient population," said Dr. Hassan, "While the findings warrant further investigation, I believe the addition of CRS-207 to the standard chemotherapy regimen used in this trial may enhance overall response rates and may boost the duration of those responses."
Dirk G. Brockstedt, Ph.D., senior vice president of Aduro added, "These early results continue to support the promise of our technology as a method to boost and rally a patient's immune system to target tumors. These data in mesothelioma are encouraging and support the notion that immunotherapy and conventional therapies such as chemotherapy have the potential to act synergistically."
The multi-center Phase 1b study enrolled 16 patients who were chemotherapy-naïve, had unresectable MPM, good performance status (ECOG 0 or 1) and adequate organ function. Under the trial design, eligible patients received two prime vaccinations 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 boost vaccinations three weeks apart. Clinically stable patients are eligible to recieve CRS-207 maintenance vaccinations every eight weeks. Subjects are followed every eight weeks until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.
As of March 31, the median time on study was 198 days (range: 88-402 days). No treatment-related serious adverse events or unexpected toxicities were observed. Treatment, follow-up and immune response evaluations are ongoing.
Aduro also announced that Dung Le, M.D. provided an overview of the company's Phase 2b ECLIPSE clinical trial of CRS-207 as a monotherapy and in combination with GVAX Pancreas in patients with metastatic pancreatic cancer in a poster session at ASCO. The ECLIPSE trial (Efficacy of Combination Listeria/GVAX Immunotherapy in the Pancreatic Cancer Setting) will involve over 20 clinical trial sites in the U.S. and Canada. The trial, which is randomized and controlled with three treatment arms, will evaluate the safety, immune response and efficacy of the combination immunotherapy of GVAX Pancreas (with low-dose cyclophosphamide (CY)) and CRS-207 compared to chemotherapy or to CRS-207 alone. The primary endpoint of the trial is overall survival.
The ECLIPSE trial follows the completed, randomized, controlled, multicenter Phase 2 trial in 93 patients in the same population, in which a statistically significant survival benefit was demonstrated in patients receiving the combination of CY/GVAX Pancreas and CRS-207 immunotherapies (Arm A) compared to patients receiving CY/GVAX Pancreas immunotherapy alone (Arm B). The median overall survival for patients receiving the combination was 6.1 months compared to 3.9 months for those receiving GVAX monotherapy.
For more information on the trials, please see clinicaltrials.org, identifier number NCT01675765 for the Phase 1b trial and NCT02004262 for the Phase 2b trial.
Mesothelioma and pancreatic cancer are among a number of potential applications for Aduro's LADD immunotherapy platform. Through a deal facilitated by the Johnson & Johnson Innovation center in California, Aduro announced last week that it has granted Janssen Biotech, Inc. an exclusive, worldwide license to certain product candidates specifically engineered for the treatment of prostate cancer based on its novel LADD immunotherapy platform in a deal valued at up to $365 million.