While 5-year survival rates for early stage disease are approximately 90%, survival drops to 30% in advanced stage disease. Symptoms preceding diagnosis are often non-specific and vague. Moreover, there is no effective screening test. As a result, over 75% of patients are diagnosed with advanced stage disease, which leads to the high mortality rate. Regardless of BRCA mutation status, patients who develop recurrent disease will all ultimately progress to develop therapy resistant disease and ultimately die. The use of PARP inhibitor maintenance therapy after either a complete or partial response to frontline platinum based therapy has demonstrated a more dramatic improvement in progression free survival, with the largest benefit noted in those patients with a BRCA mutation, followed by those whose tumors are noted to be homologous recombination deficient and lastly a modest benefit for those cancers that are BRCA wild-type and homologous recombination proficient. This trial will employ the combination of vismodegib and atezolizumab as it has been shown that inhibition of hedgehog signaling in the tumor stroma can reverse tumor desmoplasia. The benefit-risk ratio for atezolizumab in combination with vismodegib is expected to be acceptable in this setting.
This trial will treat patients with platinum resistant ovarian, fallopian tube or primary peritoneal cancer as defined by a progression free interval within six months of completion of most recent platinum-based treatment with a combination of vismodegib and atezolizumab. Despite recent improvements in treatment of ovarian cancer with the introduction of PARP inhibitors, response rates to therapy in the platinum resistant setting remain dismal with response rates of only 10-20% reported for single agent cytotoxic therapies. Given the poor prognosis and limited treatment options for these patients, this population is considered appropriate for trials of novel therapeutic candidates.