Researchers claim that they conducted a Phase I trial to assess the efficacy and safety of paclitaxel, sapanisertib, and serabelisib. This was an open-label cohort trial comparing sapanisertib (TAK-228) and serabelisib (TAK-117) to weekly paclitaxel in patients with recurrent or metastatic solid tumors. For a study, researchers employed a standard 3 + 3 dose escalation design with 5 dosing groups. The researchers also looked at results as reported by patients. Around 19 patients with severe pretreatment were enrolled (10 ovarian, 3 breasts, and 6 endometrial cancers). Prior to enrollment, thorough genetic profiling was performed on all patients. For RP2D, 3 or 4 mg of sapanisertib and 200 mg of serabelisib on days 2, 4, 9, 11, 16, and 25 of every 28-day cycle, followed by paclitaxel 80 mg/m2 on days 1, 8, and 15. There was 1 patient in Cohort 5 who had a DLT, necessitating dose reductions for the whole cohort. Decreased white blood cell count (20%), nonfebrile neutropenia (12%), anemia (9%), increased liver enzymes (4%), and hyperglycemia (11%). There were 3 complete responses, 4 partial responses, and 4 long-term stable diseases. In 15 patients who were evaluable, the ORR was 47%, and the CBR was 73%. Overall, PFS was 11 months across the entire cohort of 19, and the median OS was 17 months. Overall, patients tolerated and responded favorably to the combination of sapanisertib, serabelisib, and paclitaxel. The preliminary efficacy was impressive in a neglected region, particularly for patients with PI3K/AKT/mTOR pathway abnormalities. Positive results and persistent clinical benefit were observed in patients who had previously been resistant to platinum and who had tried and failed taxanes, everolimus, and temsirolimus.