VISMO is a first-in-class Hedgehog pathway inhibitor approved for the treatment of adult pts with advanced BCC. Pts with multiple BCCs, including those with BCC nevus syndrome, require long-term treatment with VISMO; however, continuous treatment may not be optimal over extended periods due to risk of chronic low-grade toxicity. MIKIE (NCT01815840) was designed to assess the efficacy and safety of two long-term intermittent VISMO dosing regimens in pts with multiple BCCs.
Pts with ≥1 histopathologically confirmed BCC and ≥6 clinically evident BCCs were randomized in a 1:1 ratio to receive VISMO 150 mg once daily on one of two intermittent schedules for 72 weeks: VISMO for 12 weeks alternating with placebo for 8 weeks (Regimen A), or VISMO for 24 weeks followed by placebo for 8 weeks alternating with VISMO for 8 weeks (Regimen B). The primary end point was % reduction in number of clinically evident BCC lesions from baseline to Week 73. At selected sites, samples for PK analysis were obtained at pre-dose and 2 hours post dose at Week 13, and at pre-dose at all subsequent visits. PK outcomes measured included an average plasma concentration of total and unbound VISMO. The PK analysis population included all randomized pts who received ≥1 dose of study treatment and had at least one PK assessment.
A total of 229 pts were randomized to Regimen A (n = 116) or Regimen B (n = 113). At clinical cut-off for the primary analysis (August 27, 2015), the mean reduction from baseline in the total number of clinically evident BCC lesions at Week 73 was 62.7% for Regimen A and 54.0% for Regimen B. The PK analysis population comprised 68 pts (58.6%) in Regimen A and 57 pts (50.4%) in Regimen B. PK outcomes for each study arm will be presented and discussed.
The reduction in total number of clinically evident BCCs at Week 73 demonstrates that intermittent VISMO dosing schedules are effective in pts with multiple BCCs. The PK analysis of the MIKIE study will characterize the PK profiles for each dosing regimen and will be helpful in informing PK modeling to further optimize the dosing schedule.
Clinical trial identification
Legal entity responsible for the study
D. Schadendorf: Consultant or Advisory Role: GSK, Roche, Novartis, BMS, Amgen Honoraria: GSK, Roche, Novartis, BMS, Amgen. A. Hauschild: Consulting/Advisory, Honoraria, Trial Grants: Amgen, BMS, Celgene, Eisai, GSK, MedImmune, MelaSciences, Merck Serono, MSD/Merck, Novartis, Oncosec, Roche Pharma. S. Fosko: Saint Louis University received monies on behalf of his work with Genentech with regard to consultant, advisory panel and speakers bureau activities. Funding for this clinical trial was provided by Genentech to Saint Louis University. D. Zloty: Consulting/Advisory, Honoraria, Speakers Bureau, Travel, Accommodations, Expenses: Roche. J.J. Grob: Consulting/Advisory:GSK, BMS, Roche, Amgen, Merck, Novartis Honoraria:GSK, Roche, BMS Speakers' Bureau: GSK Research Funding: Roche, BMS, author institution Travel, Accommodations, Expenses: Roche. S. Puig: Cons: Roche, BMS, AMGEN, Leo, Novartis; Honor: Roche, BMS, Merck, MSD, ISDIN, MEDA, La Roche Posay, Leo; Spkr Bur: Roche, BMS, MSD, ISDIN, La Roche Posay, Leo, Almirall, Novartis; Resrch: Roche, BMS, Merck, MEDA, La Roche Posay, Leo, Almirall, AMGEN, GSK. M. Makrutzki: Employee Hoffman-La Roche. I. Templeton: Employment, Stock or Other Ownership: Genentech. G. Rogers: Consulting/Advisory, Honoraria, Research: Genentech. B. Dreno: Consulting/Advisory: BMS, GSK, Roche, Novartis Speaker Bureau: BMS, GSK, Roche Research: BMS, GSK Travel, Accommodations, Expenses: BMS, Roche. R. Kunstfeld: Consulting/Advisory: Roche, Novartis, Menarini, Meda‐Pharma, Spirig, Leo Pharma Honoraria: Roche, Novartis, Menarini, Meda‐Pharma. All other authors have declared no conflicts of interest.