CRS-207 shows promise, says Aduro

BERKELEY, Calif.—Aduro Biotech Inc. announced June 3 the presentation of updated data from an ongoing Phase 1b clinical trial of its immunotherapy product candidate CRS-207 in combination with pemetrexed and cisplatin (standard of care chemotherapy) as front-line treatment for patients with unresectable malignant pleural mesothelioma (MPM). The results from the first of two cohorts were presented in a poster presentation at the 2016 American Society of Clinical Oncology Meeting (ASCO) held in Chicago.

Of the 36 evaluable patients, disease control was observed in 94 percent, including 3 percent with a complete response, 56 percent with partial responses and 36 percent experiencing stable disease following treatment with CRS-207 and chemotherapy. Prior to receiving chemotherapy, 31 percent of patients experienced some tumor shrinkage in the range of 1 percent to 43 percent of size after receiving CRS-207 alone. The estimated median overall survival was 16.4 months. CRS-207 was generally well-tolerated with no treatment-related serious adverse events or cumulative toxicities when administered with chemotherapy.

“The observed responses with the combination of CRS-207 and standard chemotherapy are unprecedented in mesothelioma,” said Dr. Dean Fennell, professor of thoracic medical oncology at the University of Leicester in the United Kingdom and president of the International Mesothelioma Interest Group. “Pleural mesothelioma is a devastating disease, and these data suggest that immunotherapy has the potential to advance treatment options for these patients.”

Dr. Dirk G. Brockstedt, executive vice president of research and development at Aduro added, “These results demonstrate that CRS-207 induces antitumor activity in patients with malignant pleural mesothelioma. We are looking forward to the results from the study’s second cohort, which is evaluating the addition of immune modulating doses of cyclophosphamide to the CRS-207 chemotherapy combination. Preclinical data suggest that the simultaneous inhibition of regulatory T cells through the addition of a checkpoint inhibitor may amplify the tumor response and overall survival seen with CRS-207. As such, the combination of CRS-207 with a checkpoint inhibitor could be the regimen we advance in our mesothelioma program going forward.”

The multicenter Phase 1b study enrolled chemotherapy-naïve patients with unresectable MPM and good performance status (ECOG 0 or 1) to receive two doses of CRS-207, followed by up to six cycles of chemotherapy and two additional CRS-207 doses. Clinically stable patients receive CRS-207 maintenance every eight weeks and are followed every eight weeks until disease progression. Objectives of the study are safety, immunogenicity, objective tumor responses and tumor marker kinetics.

A second cohort of 22 patients is receiving an immunomodulatory dose of cyclophosphamide one day prior to each CRS-207 administration in the same treatment regimen utilized in the first cohort. This cohort is fully enrolled and patient follow-up is ongoing.

Mesothelioma is a form of cancer that affects the smooth layer of mesothelial cells that surround the chest, lungs, heart and abdomen. 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 United States alone. MPM is an aggressive disease with a poor prognosis; most 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 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. LADD is Aduro's proprietary platform of live, attenuated double-deleted Listeria monocytogenes strains that have been engineered to generate a potent innate immune response and to express tumor-associated antigens to induce tumor-specific T cell-mediated immunity.