A phase II randomized trial of cobimetinib plus chemotherapy, with or without atezolizumab, as first-line treatment for patients with locally advanced or metastatic triple-negative breast cancer (COLET): primary analysis

•Cobimetinib plus paclitaxel trended toward a numerical increase in progression-free survival and objective response rate.•The triplet combination of atezolizumab, cobimetinib, taxane did not appear to showed trend improved rate patients with programmed death-ligand 1 (PD-L1)-positive disease.•These results demonstrate the potential activity immunotherapy for this difficult-to-treat patient subgroup. BackgroundResistance standard chemotherapy metastatic triple-negative breast cancer (mTNBC) is associated upregulation mitogen-activated protein kinase (MAPK) pathway. Cobimetinib, an MAPK/extracellular signal-regulated (MEK) inhibitor, may sensitivity taxanes inhibitors. COLET three-cohort phase II study evaluating first-line cobimetinib chemotherapy, or without locally advanced mTNBC.Patients methodsPatients were ?18 years mTNBC. Following safety run-in, cohort I randomized 1:1 (60 mg, D3-D23 each 28-day cycle) placebo, (80 mg/m2, D1, 8, 15). Additional (1:1) III receive atezolizumab (840 D1 D15) either (cohort II) nab-paclitaxel [cohort (100 D8, D15)]. Primary endpoints investigator-assessed (PFS) I) confirmed (ORR) (cohorts II/III). Safety tolerability also assessed.ResultsIn expansion stages, median PFS was 5.5 months cobimetinib/paclitaxel versus 3.8 placebo/paclitaxel [hazard ratio 0.73; 95% confidence interval (CI) 0.43-1.24; P = 0.25]. In I, ORR 38.3% (95% CI 24.40-52.20) 20.9% 8.77-33.09) placebo/paclitaxel; ORRs cohorts 34.4% 18.57-53.19) 29.0% 14.22-48.04), respectively. Diarrhea most common grade ?3 adverse events across all cohorts.ConclusionsCobimetinib added lead statistically significant ORR, although nonsignificant observed. Cobimetinib ORR. This demonstrates combinatorial MEK population. Resistance Patients assessed. cohorts.