Aduro Biotech, Inc., a clinical-stage immuno-oncology company, has completed enrollment in the 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).

The multi-center phase 1b trial enrolled 38 patients who were chemotherapy-naïve, had unresectable MPM, had good performance status (ECOG 0 or 1), and adequate organ function. The company plans to advance directly to a phase 3 clinical trial with CRS-207 in combination with standard-of-care chemotherapy in patients with unresectable MPM in the first half of 2016.

"Based on compelling data from the phase 1b trial, as well as recent meetings with the US Food and Drug Administration, Paul-Ehrlich-Institut and thought leaders in the field, we believe that we have strong rationale to advance the combination regimen with CRS-207 into a pivotal phase 3 clinical trial in the front-line setting," said Dirk G. Brockstedt, Ph.D., senior vice president of research and development at Aduro.

"We expect this approach may accelerate our ability to offer patients with mesothelioma, a particularly grievous and aggressive disease, an attractive therapeutic alternative. We are currently working with our key clinical advisors and regulatory authorities to finalize the design of a global Phase 3 pivotal study."

Thomas Dubensky, Ph.D., chief scientific officer at Aduro, added, "We are thrilled to advance our LADD technology into another late-stage programme. We believe this platform offers significant promise in generating potent innate and tumor-specific adaptive immune responses and we look forward to continuing to explore its potential as a therapeutic alternative for patients."

In the phase 1b trial, 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 received CRS-207 maintenance vaccinations every eight weeks and were followed every eight weeks until disease progression. Objectives of the study were safety, immunogenicity, objective tumour responses and tumour marker kinetics.

Interim data presented at the 2015 American Society of Clinical Oncology Meeting (ASCO) indicate that the combination of CRS-207 with standard-of-care chemotherapy may elicit strong and durable responses in patients with unresectable MPM. Of the 32 evaluable patients enrolled at the time, disease control was observed in 94 per cent (30/32), including 60 per cent (19/32) with partial responses and 34 per cent (11/32) experiencing stable disease following treatment with CRS-207 and chemotherapy.

The study sites will remain open to enroll an additional cohort of patients who will receive low-dose cyclophosphamide with CRS-207 and standard-of-care chemotherapy. Preclinical data indicate this combination may further enhance immune response, tumour-specific efficacy and overall survival.

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 estimated 13,000 cases a year worldwide. 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 tumours.

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 tumour-associated antigen mesothelin, which is over-expressed in many cancers including mesothelioma and pancreatic, non-small cell lung, ovarian and gastric cancers.