Results from a biomarker study to accompany a phase II trial of RRx-001 with reintroduced platinum-based chemotherapy in relapsed small cell carcinoma.

Background

In a Phase II study RRx-001 was combined with Etoposide platinum (EP) in previously platinum treated SCLC. We correlated expression of the M2 marker, CD206, on HLA-DRlow/- monocytes, a phenotype that correlates with a poor prognosis, with response to RRx-001. Research design and methods: Patients received 4 mg RRx-001 once weekly until progression followed by the start of EP (etoposide 100 mg/m2 IV on days 1-3 of a 21-day cycle and either cisplatin 80 mg/m2 IV on day 1 or carboplatin AUC 5-6 IV on day 1). Treatment continued until progression or intolerable toxicity. Peripheral blood was collected in Cell Preparation Tubes with sodium citrate from 14 patients for exploratory studies during screening and after therapy on Days 1, 8, and 15. Peripheral blood mononuclear cells (PBMCs) were isolated from blood by centrifugation and multiparameter flow cytometric analysis was performed.

Results

CD206 expression on HLA-DRlow/- monocytes was associated with response to chemotherapy and overall survival.

Conclusion

During treatment with RRx-001, reduced expression of the protumorigenic M2 marker CD206 on peripheral monocytes positively correlated with increased response and survival.