A phase Ib/II trial of atezolizumab with cobimetinib or idasanutlin in metastatic estrogen receptor positive breast cancer.

Despite the availability of numerous treatment options for metastatic estrogen receptor positive breast cancer, additional strategies are needed, particularly when tumors become endocrine resistant. This phase Ib/II study examined the clinical activity and safety of the novel combination of atezolizumab with molecularly targeted therapy inhibiting 1) the Ras/Raf/MEK signaling pathway with cobimetinib in TP53-mutant tumors (arm COBI) or 2) the TP53 regulator MDM2 with idasanutlin in TP53-wild-type tumors (arm IDA). Twelve patients were enrolled before the study closed early due to slow accrual. 2/7 patients in arm IDA had durable responses to treatment. 1/5 patients in arm COBI had stable disease. Interestingly, conservation of tumor-specific HLA-ABC expression was observed in nearly all patients with clinical benefit. There were several grade 3-4 toxicities, particularly cytopenias in arm IDA. While this study was limited by small sample sizes, there were observations of clinical activity, including one exceptional responder, that warrant further investigation.