Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies
In preclinical studies, the mTORC1/2 inhibitor sapanisertib restored sensitivity to platinum-based therapies and enhanced paclitaxel-induced cancer cell death. The phase I clinical trial NCT03430882 enrolled patients with tumors exhibiting mTOR pathway alterations to receive a combination of sapanisertib, carboplatin, and paclitaxel. The primary objective was to assess safety; secondary objectives included clinical response and survival outcomes.
At dose level 4, one patient experienced a dose-limiting toxicity. No unexpected toxicities were reported. Grade 3–4 treatment-related adverse events included anemia (21%), neutropenia (21%), thrombocytopenia (10.5%), and transaminitis (5%).
Among 17 evaluable patients, 2 achieved partial responses and 11 had stable disease. Notable responders included a patient with unclassified renal cell carcinoma harboring an EWSR1–POU5F1 fusion and a patient with castration-resistant prostate cancer with PTEN loss. The median progression-free survival was 3.84 months.
Overall, sapanisertib combined with carboplatin and paclitaxel showed a manageable safety profile and early signs of antitumor activity in advanced cancers with ART0380 mTOR pathway aberrations.