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

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• The mTORC1/2 inhibitor sapanisertib demonstrated preclinical efficacy in restoring platinum sensitivity and enhancing paclitaxel activity.
• Aberrant mTOR pathway signaling is implicated in various advanced malignancies, presenting a therapeutic target.

Purpose of the Study:

• To evaluate the safety and efficacy of sapanisertib in combination with carboplatin and paclitaxel in patients with mTOR pathway aberrant tumors.
• To assess clinical response and survival outcomes in this patient cohort.

Main Methods:

• A Phase I/II clinical trial (NCT03430882) enrolled patients with mTOR pathway aberrant tumors.
• Patients received sapanisertib, carboplatin, and paclitaxel, with safety, clinical response, and survival as primary and secondary objectives.

Main Results:

• The combination therapy exhibited a manageable safety profile with no unanticipated toxicities. Grade 3-4 treatment-related adverse events included anemia, neutropenia, and thrombocytopenia.
• Among 17 evaluable patients, 2 achieved partial response and 11 had stable disease. Notable responses were seen in unclassified renal cell carcinoma and castrate-resistant prostate cancer.
• Median progression-free survival was 3.84 months.

Conclusions:

• Sapanisertib combined with carboplatin and paclitaxel demonstrates a manageable safety profile in advanced malignancies with mTOR pathway alterations.
• Preliminary antitumor activity suggests potential therapeutic benefit, warranting further investigation of this combination regimen.