On October 23, 2014 Aduro BioTech reported the presentation of updated safety and efficacy data from an ongoing Phase 1b clinical trial of its novel immunotherapy CRS-207 in combination with standard chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM) (Press release Aduro BioTech, OCT 23, 2014, View Source [SID:1234500871]). Of 16 evaluable patients with response data, 75% (12/16) had confirmed durable partial responses (PR) and 19% (3/16) experienced stable disease (SD) after CRS-207 and chemotherapy, for a 94% rate of disease control (PR and SD). At the time of the presentation, estimated progression-free survival was 7.5 months with one patient on study for more than 19 months, currently receiving maintenance therapy with CRS-207 following the combination treatment.
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The results were presented by Raffit Hassan, M.D., winner of the 2014 Wagner Medal for his career work in mesothelioma and co-chief of the Thoracic and GI Oncology Branch at the National Cancer Institute, in an oral presentation at the International Mesothelioma Interest Group (iMig) Conference held in Cape Town, South Africa. 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.
"We continue to be excited by the results from this trial of our novel immunotherapy in combination with chemotherapy in this difficult-to-treat patient population," said Stephen T. Isaacs, chairman, president and chief executive officer of Aduro. "While the findings warrant further investigation, we believe CRS-207 may prove to be a very attractive therapeutic option in the armamentarium to improve overall response rates and boost the duration of those responses."
Dirk G. Brockstedt, Ph.D., senior vice president of research and development at Aduro, added, "These results continue to support the promise of our technology as a method to boost and rally a patient’s immune system to target tumors. We plan to further evaluate CRS-207 in combination with chemotherapy in a randomized, controlled Phase 2 clinical trial in mesothelioma, which we anticipate to begin in the first half of 2015."
The multi-center Phase 1b study is open to patients with unresectable MPM who are chemotherapy-naïve, have good performance status (ECOG 0 or 1) and adequate organ function. Under the trial design, eligible patients receive 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 then two CRS-207 boost vaccinations three weeks apart. Clinically stable patients are eligible to receive CRS-207 maintenance vaccinations every eight weeks. Subjects are followed every eight weeks until disease progression. Objectives of the study are to assess safety, immunogenicity, objective tumor responses and tumor marker kinetics. Twenty-three patients have been enrolled thus far and additional response, follow-up and immune response data are pending.
At the time of the presentation, the median time on study was 229 days (range: 155-570 days). No treatment-related serious adverse events or unexpected toxicities were observed. The most common adverse events associated with CRS-207 were infusion-related chills and fever, which were transient, mild and self-limiting.