Phase I study of sapanisertib with carboplatin and paclitaxel in mTOR pathway altered solid malignancies

Pre-clinically, the mTORC1/2 inhibitor sapanisertib restored sensitivity to platinums and enhanced paclitaxel-induced cancer cell killing. NCT03430882 enrolled patients with mTOR pathway aberrant tumors to receive sapanisertib, carboplatin and paclitaxel. Primary objective was safety and secondary o...

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Published in:NPJ precision oncology 2023-04, Vol.7 (1), p.37-37, Article 37
Main Authors: Alhalabi, Omar, Groisberg, Roman, Zinner, Ralph, Hahn, Andrew W., Naing, Aung, Zhang, Shizhen, Tsimberidou, Apostolia M., Rodon, Jordi, Fu, Siqing, Yap, Timothy A., Hong, David S., Sun, Ming, Jiang, Yunfang, Pant, Shubham, Shah, Amishi Y., Zurita, Amado, Tannir, Nizar M., Vikram, Raghunandan, Roszik, Jason, Meric-Bernstam, Funda, Subbiah, Vivek
Format: Article
Language:English
Subjects:
631/154/1438
692/4028/67/1059/153
Cancer
Cancer Research
Chemotherapy
Gene Therapy
Human Genetics
Inflammation
Inhibitor drugs
Internal Medicine
Kidney cancer
Medicine
Medicine & Public Health
Neutropenia
Oncology
Prostate cancer
Protocol
Side effects
Targeted cancer therapy
Thrombocytopenia
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Summary:Pre-clinically, the mTORC1/2 inhibitor sapanisertib restored sensitivity to platinums and enhanced paclitaxel-induced cancer cell killing. NCT03430882 enrolled patients with mTOR pathway aberrant tumors to receive sapanisertib, carboplatin and paclitaxel. Primary objective was safety and secondary objectives were clinical response and survival. One patient had a dose-limiting toxicity at dose level 4. There were no unanticipated toxicities. Grade 3–4 treatment-related adverse events included anemia (21%), neutropenia (21%), thrombocytopenia (10.5%), and transaminitis (5%). Of 17 patients evaluable for response, 2 and 11 patients achieved partial response and stable disease, respectively. Responders included a patient with unclassified renal cell carcinoma harboring EWSR1-POU5F1 fusion and a patient with castrate resistant prostate cancer harboring PTEN loss. Median progression free survival was 3.84 months. Sapanisertib in combination with carboplatin plus paclitaxel demonstrated a manageable safety profile, with preliminary antitumor activity observed in advanced malignancies harboring mTOR pathway alterations.
ISSN:2397-768X
2397-768X
DOI:10.1038/s41698-023-00369-w