Phase II study of atezolizumab in combination with bevacizumab in patients with advanced cervical cancer

Claire F Friedman, Alexandra Snyder Charen, Qin Zhou, Michael A Carducci, Alexandre Buckley De Meritens, Bradley R Corr, Siqing Fu, Travis J Hollmann, Alexia Iasonos, Jason A Konner, Panagiotis A Konstantinopoulos, Susan C Modesitt, Elad Sharon, Carol Aghajanian, Dmitriy Zamarin, Claire F Friedman, Alexandra Snyder Charen, Qin Zhou, Michael A Carducci, Alexandre Buckley De Meritens, Bradley R Corr, Siqing Fu, Travis J Hollmann, Alexia Iasonos, Jason A Konner, Panagiotis A Konstantinopoulos, Susan C Modesitt, Elad Sharon, Carol Aghajanian, Dmitriy Zamarin

Abstract

Background: There are limited treatment options for patients with metastatic or recurrent cervical cancer. Platinum-based chemotherapy plus the anti-vascular endothelial growth factor antibody bevacizumab remains the mainstay of advanced treatment. Pembrolizumab is Food and Drug Agency approved for programmed death ligand 1 (PD-L1) positive cervical cancer with a modest response rate. This is the first study to report the efficacy and safety of the PD-L1 antibody atezolizumab in combination with bevacizumab in advanced cervical cancer.

Methods: We report the results from a phase II, open-label, multicenter study (NCT02921269). Patients with advanced cervical cancer were treated with bevacizumab 15 mg/kg intravenous every 3 weeks and atezolizumab 1200 mg intravenous every 3 weeks. The primary objective was to measure the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results: In the total evaluable population (n=10), zero patients achieved an objective response as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1, resulting in a confirmed ORR of 0%. Of note, there were two patients who achieved an unconfirmed PR. The DCR by RECIST V.1.1 was 60% (0% complete response, 0% partial response, 60% stable disease). Median PFS was 2.9 months (95% CI, 1.8 to 6) and median OS was 8.9 months (95% CI, 3.4 to 21.9). Safety results were generally consistent with the known safety profile of both drugs, notably with two high-grade neurologic events.

Conclusions: The combination of bevacizumab and atezolizumab did not meet the predefined efficacy endpoint, as addition of bevacizumab to PD-L1 blockade did not appear to enhance the ORR in cervical cancer.

Keywords: combination; drug therapy; female; genital neoplasms; programmed cell death 1 receptor; tumor biomarkers.

Conflict of interest statement

Competing interests: DZ reports clinical research support to his institution from Astra Zeneca and Genentech; personal/consultancy fees from Merck, Synlogic Therapeutics, Biomed Valley Discoveries, Trieza Therapeutics, Tesaro, Bristol Myers Squibb, and Agenus; and travel support from Genenetech. These are all outside of the scope of the submitted work. CF reports clinical research support to her institution from Merck, Bristol Myers Squibb and Genentech; personal/consultancy fees from Astra Zeneca, as well as participation in steering committees (compensation waived) for Merck and Genentech. These are outside the scope of the submitted work. AS reports that she is now an employee of Merck and declares Merck stock ownership. ABM reports no conflicts of interest. SF reports clinical research support to his institution from the following: AstraZeneca; Abbisko; Anaeropharma Science; Arrien Pharmaceuticals; BeiGene; BioAtla, LLC; Boehringer Ingelheim; Eli Lilly & Co; Hookipa Biotech GmBH; Huya Bioscience International; IMV, Inc; Innovent Biologics, Co, Ltd; Lyvgen Biopharm, Co, Ltd; MacroGenics; Medivir AB; Millennium Pharmaceuticals, Inc; Nerviano Medical Sciences; NeuPharma, Inc; NIH/NCI; Novartis; OncoMed Pharmaceuticals; Parexel International, LLC; Sellas Life Sciences Group; Soricimed Biopharma, Inc; Tolero Pharmaceuticals. BC reports advisory committees for GSK, Novocure, and Merck. He reports research funding from Clovis. These are all outside the scope of the submitted work. TH reports research funding from Bristol Myers Squibb which is outside the scope of the submitted work.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Clinical efficacy of atezolizumab plus bevacizumab in patients with advanced cervical cancer. (A) Spider plot of target lesions assessed per RECIST V.1.1. (B) PFS. (C) OS. OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria In Solid Tumors.
Figure 2
Figure 2
Baseline tumor microenvironment and genomic characteristics of the treated patients. (A) Representative multiparameter immunofluorescence images from the patients with SqCC and AdC in CB and no benefit (NB) groups. (B) Heatmaps of the indicated staining parameters performed in tumor and stromal regions. (C) Quantification of the individual indicated immune cell populations in tumor and stroma separated by benefit versus no benefit. (D) Quantification of PD-L1+ and CD31+ cells in tumor and stroma separated by benefit versus no benefit. (E) Targeted genetic sequencing results from the archival tissues from six patients with available data. AdC, adenocarcinoma; CB, clinical benefit; PD-L1, programmed death ligand 1; SqCC, squamous cell carcinoma; TMB, tumor mutational burden.

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