Roche provides details on vismodegib proof-of-concept in advanced skin cancer
Basel/Nantes – Roche has presented details of its clinical Phase II proof-of-concept study with its sonic hedgehog pathway blocker vismodegib (RG3616/GDC-0449) on patients with advanced basal cell carcinoma. The single-arm, two-cohort, open-label study enrolled 104 patients with advanced BCC, including laBCC and mBCC. The 71 laBCC patients had lesions that were inappropriate for surgery (inoperable, or for whom surgery would result in substantial deformity) and for which radiotherapy was unsuccessful or contraindicated. mBCC (33 patients) was defined as BCC that had spread to other parts of the body, including the lymph nodes, lung, bones and/or internal organs. Study participants received 150mg vismodegib orally, once daily until disease progression or intolerable toxicity. Overall response rate was 43 percent in the laBCC cohort, and 30 percent in the mBCC group. Progression-free survival (PFS) for both metastatic and locally advanced BCC patients was 9.5 months. The clinical benefit rate – defined as patients who experienced response as well as prolonged stable disease for more than 24 weeks – showed vismodegib shrank tumours or healed visible lesions, or prevented them from growing any further in 75 percent of patients. As announced in March, the most common adverse events included muscle spasms, hair loss, altered taste sensation, weight loss, fatigue, nausea, decreased appetite and diarrhoea. Serious adverse events (SAEs) were observed in 25 percent of patients, but only 4 percent were considered to be related to treatment with vismodegib. Fatal events were reported in 7 percent of patients but none were considered by investigators to be related to treatment with vismodegib. In all cases, patients had other pre-existing diseases or symptoms that were related to their presumed cause of death. Vismodegib was developed by Roche in collaboration with Curis Inc. for BCC, colorectal cancer and medulloblastoma, all of which show activation of sonic hedgehog signalling.