Aduro Presents Positive Early Data from Phase 1b Mesothelioma Trial Evaluating Combo Treatment

Aduro Presents Positive Early Data from Phase 1b Mesothelioma Trial Evaluating Combo Treatment

Combining the cancer vaccine CRS-207 with standard of care chemotherapy and cyclophosphamide looks like a promising first-line treatment for patients with unresectable malignant pleural mesothelioma, according to preliminary data from the second cohort of an ongoing Phase 1b trial, recently presented by Aduro Biotech.

The poster presentation took place at the Society for Immunotherapy of Cancer (SITC) 2016 Annual Meeting Nov. 9-13 in National Harbor, Maryland, and revealed promising anti-tumor activity, with more than half of patients achieving a partial response to treatment.

The mesothelioma trial is an open-label, Phase 1b safety and effectiveness study (NCT01675765) evaluating the cancer vaccine CRS-207, a weakened and genetically altered form of Listeria monocytogenes that activates immune cells to recognize mesothelin-expressing tumors.

The vaccine is being assessed in combination with Alimta (pemetrexed) and Platinol (cisplatin) chemotherapy, with or without cyclophosphamide, as a front-line therapy for adult malignant pleural mesothelioma patients.

The poster presentation included preliminary data from 22 patients in the second cohort of the trial and demonstrated an 82 percent disease control rate, with a partial response seen in 55 percent of patients, and stable disease achieved in 27 percent of patients.

The data also showed that the combination treatment resulted in tumor shrinkage in 77 percent of patients (17 of 22), eight of whom experienced tumor shrinkage after two doses of cyclophosphamide combined with CRS-207, but before chemotherapy initiation. A partial response was seen in 14 percent of these combo-treated patients. There were no reports of serious adverse events or unexpected toxicities.

Compared to baseline, two patients treated with two doses of cyclophosphamide in combination CRS-207 exhibited a marked infiltration of immune effector cells into the tumor microenvironment (TME), including CD8-positive T-cells and dendritic cells.

These preliminary results indicate that the combo treatment-induced remodeling of the TME may be an important component of the clinical responses seen in these 22 patients.

“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,” Dirk G. Brockstedt, PhD, executive vice president of research and development for Aduro, said in a press release.

“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,” he added.

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