Incyte announces positive results from ongoing Phase I/II clinical trial for INCB7839

Incyte Corporation (Nasdaq:INCY) announced today positive results from an ongoing Phase I/II clinical trial for its selective oral sheddase inhibitor, INCB7839, involving 46 patients with HER2 positive metastatic breast cancer. The results suggest that, when compared to a historical control study of trastuzumab as monotherapy, INCB7839 in combination with trastuzumab provided improvements in time to progression and response rate in patients with HER2 positive metastatic breast cancer. These improved outcomes were achieved despite the presence of more advanced disease in the study population when compared to the historical control (Baselga et al, 2005).

The improved response rate observed in this study are thought to result from an increased response in the p95HER2 positive subpopulation>

In this study, the combination of INCB7839 and trastuzumab was generally well tolerated with no EGFR kinase related toxicities (rash, diarrhea), no MMP inhibitor related toxicities (musculoskeletal), and no drug related liver enzyme elevations or bone marrow toxicities. There was also no increase in cardiomyopathy (5/46 patients experienced cardiomyopathy) and no increase in thrombotic events (5/46 patients experienced a thrombotic event) from that expected for this population. All patients received low dose warfarin and low dose aspirin daily because of prior data associating INCB7839 with an increased thrombosis risk and the high underlying rate of thrombosis in this patient population.

The 7839-202 study also demonstrated that INCB7839 significantly decreased the level of plasma ErbB ligands, another marker of poor clinical outcomes. In a separate poster researchers at Incyte showed that the ErbB ligands can circumvent the anti-tumor activity of trastuzumab and lapatinib for HER2+ breast cancer cell lines. ErbB ligand-induced resistance appeared to be mediated by signaling through p95HER2 and, by inhibiting sheddase activity, INCB7839 restored the anti-tumor activity of trastuzumab and lapatinib in the presence of ErbB ligands.