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

被引：6

作者：

Alhalabi, Omar ^{[1
,2
]}

Groisberg, Roman ^{[3
]}

Zinner, Ralph ^{[4
]}

Hahn, Andrew W. ^{[5
]}

Naing, Aung ^{[2
]}

Zhang, Shizhen ^{[2
]}

Tsimberidou, Apostolia M. ^{[2
]}

Rodon, Jordi ^{[2
]}

Fu, Siqing ^{[2
]}

Yap, Timothy A. ^{[2
]}

Hong, David S. ^{[2
]}

Sun, Ming ^{[2
]}

Jiang, Yunfang ^{[2
]}

Pant, Shubham ^{[2
]}

Shah, Amishi Y. ^{[1
]}

Zurita, Amado ^{[1
]}

Tannir, Nizar M. ^{[1
]}

Vikram, Raghunandan ^{[6
]}

Roszik, Jason ^{[7
,8
]}

Meric-Bernstam, Funda ^{[2
]}

Subbiah, Vivek ^{[2
]}

机构：

[1] Univ Texas MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Div Canc Med, Houston, TX USA

[2] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, Div Canc Med, Houston, TX 77030 USA

[3] Rutgers State Univ, Dept Med Oncol, New Jersey, NJ USA

[4] Univ Kentucky, Dept Thorac Oncol, Lexington, KY USA

[5] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX USA

[6] Univ Texas MD Anderson Canc Ctr, Dept Abdominal Imaging, Div Diagnost Imaging, Houston, TX USA

[7] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Div Canc Med, Houston, TX USA

[8] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Div Canc Med, Houston, TX USA

来源：

NPJ PRECISION ONCOLOGY | 2023年 / 7卷 / 01期

关键词：

INHIBITION; TUMORS; EVEROLIMUS;

D O I：

10.1038/s41698-023-00369-w

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页数：10

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