Purpose We investigated the mixture from the MEK inhibitor, cobimetinib, and also the pan-PI3K inhibitor, pictilisib, within an open-label, phase Ib study. Experimental Design Patients with advanced solid tumors were signed up for 3 dose escalation schedules: (1) both agents once-daily for 21-days-on 7-days-off (“21/7″) (2) intermittent cobimetinib and 21/7 pictilisib (“intermittent”) or (3) both agents once-daily for 7-days-on 7-days-off (“7/7″). Beginning doses for that 21/7, intermittent, and sevenOrseven schedules were 20/80, 100/130, and 40/130 mg of cobimetinib/pictilisib, correspondingly. Nine indication-specific expansion cohorts interrogated the suggested phase II dose and schedule. Outcomes Of 178 enrollees (dose escalation: n = 98), 177 patients were dosed. The utmost tolerated doses for cobimetinib/pictilisib (mg) were 40/100, 125/180, and never arrived at, for that 21/7, intermittent, and sevenOrseven schedules, correspondingly. Six dose-restricting toxicities incorporated grade 3 (G3) elevated lipase, G4 elevated creatine phosphokinase, and G3 occasions including fatigue concurrent having a serious adverse event (SAE) of diarrhea, decreased appetite, and SAEs of hypersensitivity and lack of fluids. Common drug-related adverse occasions incorporated nausea, fatigue, vomiting, decreased appetite, dysgeusia, rash, and stomatitis. Pharmacokinetic parameters from the drugs utilized in combination were unaltered when compared with monotherapy exposures. Confirmed partial responses were noticed in patients with BRAF-mutant melanoma (n = 1) and KRAS-mutant endometrioid adenocarcinoma (n = 1). 18 patients continued to be on study ≥6 several weeks. Biomarker data established effective blockade of MAP kinase (MAPK) and PI3K pathways. The metabolic response rate documented by FDG-PET looked like that observed with cobimetinib monotherapy. Conclusions Cobimetinib and pictilisib combination therapy in patients with solid tumors had limited tolerability and effectiveness.