Aduro reports on mesothelioma trial
BERKELEY, Calif.—Aduro Biotech Inc. recently announced preliminary data from an ongoing Phase 1 clinical study on the safety and efficacy of its novel immunotherapy, CRS-207, in unresectable malignant pleural mesothelioma in a poster presentation at the Annual Meeting of the Society for Immunotherapy of Cancer in National Harbor, Md. The findings reported were from the second cohort of patients using CRS-207 in combination with standard-of care-chemotherapy and immune-modulating doses of cyclophosphamide as a first-line treatment.
As of October 2016, of the 22 patients in that second cohort, 82 percent of patients had disease control, with 55 percent of patients achieving a partial response and 27 percent with stable disease. Also reported was tumor shrinkage observed in 77 percent, 36 percent responding after two doses of immunomodulatory doses of cyclophosphamide combined with CRS-207, but prior to initiation of standard-of-care chemotherapy. No treatment-related serious adverse events or unexpected toxicities were observed. Additional analysis of paired tumor biopsies obtained from two patients showed a marked infiltration of immune effector cells into the tumor microenvironment following two doses of CRS-207, and post-therapeutic changes included an increase in CD8+ cytotoxic T cells as well as an increase in other immune cell types that are thought to be essential for effective immunotherapy, including dendritic cells and natural killer cells, correlating with other positive clinical outcome.
“The data from the second cohort, which is a patient population with more advanced disease compared to the first cohort, demonstrate that the addition of immunomodulatory doses of cyclophosphamide, which has been shown to inhibit negative regulatory T cell populations, to the combination of CRS-207 and chemotherapy results in encouraging disease control and tolerability for patients with mesothelioma,” commented Dr. Dirk G. Brockstedt, executive vice president of research and development of Aduro. “Importantly, we believe these data, together with the results from the first cohort, support further investigation of CRS-207 in mesothelioma, and we intend to initiate a Phase 2 study of CRS-207 used in combination with an anti-PD-1 therapy as an immune-modulator in patients with mesothelioma who have failed at least one prior therapy.”
Aduro has had an interest in mesothelioma for some time, the basis for this research stemming from work done at Johns Hopkins University regarding GVAX. GVAX is a therapeutic cancer vaccine being investigated for its use in combination therapy in patients with pancreatic cancer, and Aduro is currently evaluating CRS-207 and GVAX Pancreas in combination with the checkpoint inhibitor, nivolumab, in the STELLAR trial, a Phase 2 randomized controlled trial in patients with metastatic pancreatic cancer.
“This has been studied for decades,” Brockstedt stated in an interview with DDNews regarding the use of the body’s innate immunity to trigger T cell response. “The first step was to develop a strain that was safe for patients.” He added that over 400 subjects have been treated specifically using Listeria, with most of the reactions being infusion site-related reactions and flu-like symptoms.
The initial cohort in the CRS-207 study started with 16 patients, but with promising results was expanded to 36 patients. While the first cohort experienced a pure combination therapy with two doses of CRS-207 given two weeks apart, the second cohort was given a low dose of cyclophosphamide 24 hours before the first dose of CRS-207. Due to the low patient number, Aduro is working on expanding data and hopes to report on the progression of this study in the next year, including an assessment of the difference between the two cohorts and whether or not varying results could be due to the difference in patients or treatments. Encouraged by the results observed in Phase 1 and preclinical data on immune modulation, Phase 2 is planned for the first half of 2017.
Aduro is an immunotherapy company focused on the discovery, development and commercialization of therapies that transform the treatment of challenging diseases. Aduro’s three 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.
CRS-207 is one of a family of product candidates based on Aduro’s LADD immunotherapy platform that 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.