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.
| Original language | English |
|---|---|
| Article number | 37 |
| Journal | npj Precision Oncology |
| Volume | 7 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 2023 |
Bibliographical note
Publisher Copyright:© 2023, The Author(s).
Funding
The authors thank all the patients who participated in these studies and their families, as well as all the investigators and site staff who helped conduct this study. We would like to acknowledge the late Dr. Kenneth R. Hess, PhD who made valuable contributions to statistical design of this study. V. Subbiah is an Andrew Sabin Family Foundation Fellow at The University of Texas MD Anderson Cancer Center. V. Subbiah acknowledges support of The Jacquelyn A. Brady Fund. V. Subbiah is supported by NIH grant R01CA242845. MD Anderson Cancer Center Department of Investigational Cancer Therapeutics is supported by the Cancer Prevention and Research Institute of Texas (RP1100584), the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (1U01 CA180964), the Center for Clinical and Translational Sciences (NCATS) Grant UL1 TR000371, and the MD Anderson Cancer Center Support Grant (P30 CA016672). Figure was created with BioRender.com. This study was supported by Millennium Pharmaceuticals Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. The funders had no role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication. Final approval of manuscript: All authors. Agree to be accountable for all aspects of the work, which includes ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: All authors. Trial results were in part presented as an e-poster at the virtual AACR Annual Meeting 2021.
| Funders | Funder number |
|---|---|
| Millennium Pharmaceuticals Inc | |
| National Institutes of Health (NIH) | R01CA242845 |
| Cancer Prevention and Research Institute of Texas | RP1100584 |
| National Center for Advancing Translational Sciences (NCATS) | UL1 TR000371 |
| University of Texas Anderson Cancer Center | P30 CA016672 |
| Center for Clinical and Translational Sciences, University of Texas Health Science Center at Houston | |
| Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy | 1U01 CA180964 |
ASJC Scopus subject areas
- Oncology
- Cancer Research
