Phase I Study of Bevacizumab and Temsirolimus Combination Therapy in Advanced Malignancies: Safety, Efficacy, and Ovarian Cancer Expansion

Authors

Sarina A Piha-Paul
Chieh Tseng
Emily Thompson
R Jason Stafford
Hung Le
Lei Kang
Siqing Fu
Apostolia Tsimberidou
George Blumenschein
Jordi Rodon Ahnert
John M Slopis
David Hong
Aung Naing
Funda Meric-Bernstam
Chaan S Ng
Shannon Westin
Anil K Sood

Publication Date

2-5-2026

Journal

The Oncologist

DOI

10.1093/oncolo/oyaf413

PMID

41389341

PMCID

PMC12923152

PubMedCentral® Posted Date

12-13-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Background: Bevacizumab and temsirolimus target angiogenic and mTOR pathways in cancer progression.

Methods: This phase I study enrolled 48 heavily pretreated patients with advanced solid tumors, including an ovarian cancer expansion cohort. Patients received bevacizumab biweekly plus temsirolimus weekly in a 3 + 3 design to assess safety, maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs). Exploratory analyses included tumor genomic profiling and dynamic contrast-enhanced MRI (DCE-MRI).

Results: Patients had a median age of 59 and median four prior therapies. Common tumor types were ovarian (27%) and head and neck (15%). Treatment-related adverse events occurred in 93.8%, with 31.3% ≥grade 3. Five patients experienced DLTs, including grade 3 enteritis, fatigue, bowel obstruction/abdominal ileus/pulmonary embolism, bowel perforation and grade 3/4 elevated liver enzymes. MTD was bevacizumab 10 mg/kg biweekly plus temsirolimus 20 mg weekly. Overall, objective response rate (ORR) was 7.3% and 19.5% achieved stable disease ≥6 months (clinical benefit rate [CBR] 26.8%). In ovarian cohort, ORR was 16.7% and CBR 33.3%. Patients with tumor regression on DCE-MRI had lower ΔKtrans values.

Conclusion: Combination therapy showed acceptable safety and modest activity. Molecular and imaging findings were exploratory and limited. These preliminary observations could inform future biomarker studies. (ClinicalTrials.gov Identifier: NCT01552434).

Keywords

Humans, Female, Bevacizumab, Middle Aged, Sirolimus, Ovarian Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Aged, Adult, Maximum Tolerated Dose, phase I trial, bevacizumab, temsirolimus, mTOR inhibitor, anti-VEGF

Published Open-Access

yes

Recommended Citation

Piha-Paul, Sarina A; Tseng, Chieh; Thompson, Emily; et al., "Phase I Study of Bevacizumab and Temsirolimus Combination Therapy in Advanced Malignancies: Safety, Efficacy, and Ovarian Cancer Expansion" (2026). Faculty, Staff and Student Publications. 6319.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6319