Phase I Study of Sapanisertib With Carboplatin and Paclitaxel in mTOR Pathway Altered Solid Malignancies

Authors

Omar Alhalabi
Roman Groisberg
Ralph Zinner
Andrew W Hahn
Aung Naing
Shizhen Zhang
Apostolia M Tsimberidou
Jordi Rodon
Siqing Fu
Timothy A Yap
David S Hong
Ming Sun
Yunfang Jiang
Shubham Pant
Amishi Y Shah
Amado Zurita
Nizar M Tannir
Raghunandan Vikram
Jason Roszik
Funda Meric-Bernstam
Vivek Subbiah

Publication Date

4-18-2023

Journal

NPJ Precision Oncology

Abstract

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.

Keywords

Drug development, Drug safety

DOI

10.1038/s41698-023-00369-w

PMID

37072571

PMCID

PMC10113233

PubMedCentral® Posted Date

4-18-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes