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Gynecol Oncol. 2019 Aug;154(2):314-322. doi: 10.1016/j.ygyno.2019.05.021. Epub 2019 Jun 14.

Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers.

Author information

1
Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215-5450, United States. Electronic address: Joyce_Liu@dfci.harvard.edu.
2
HonorHealth Research Institute, 10510 N 92nd St, Suite 200, Scottsdale, AZ 85258, United States. Electronic address: Michael.Gordon@HonorHealth.com.
3
University of Chicago Medicine, 5841 S Maryland Ave, Chicago, IL 60637, United States. Electronic address: Jennifer_Veneris@dfci.harvard.edu.
4
Comprehensive Cancer Centers of Nevada, 3730 S Eastern Avenue, Las Vegas, NV 89169, United States. Electronic address: fadi.braiteh@usoncology.com.
5
The Angeles Clinic and Research Institute, 11818 Wilshire Blvd #200, Los Angeles, CA 90025, United States. Electronic address: abalmanoukian@theangelesclinic.org.
6
Yale Cancer Center, Medical Oncology, PO Box 208028, New Haven, CT 06520-8028, United States. Electronic address: joseph.eder@yale.edu.
7
Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Centro Cellex, Calle Natzaret, 115-117, 08035 Barcelona, Spain. Electronic address: aoaknin@vhio.net.
8
Tennessee Oncology/Sarah Cannon Research Institute, 250 25th Ave N, Nashville, TN 37203, United States. Electronic address: ehamilton@tnonc.com.
9
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: wang.yulei@gene.com.
10
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: sarkar.indrani@gene.com.
11
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: molinero.luciana@gene.com.
12
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: fasso.marcella@gene.com.
13
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: ohearc@gene.com.
14
Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: lin-liu.yvonne@gene.com.
15
UPMC Hillman Cancer Center, 300 Halket St, Suite 4628, Pittsburgh, PA 15213, United States. Electronic address: emensla@upmc.edu.

Abstract

OBJECTIVE:

Patients with advanced/recurrent epithelial ovarian and uterine cancers have limited treatment options beyond platinum chemotherapy. Both tumor types can express programmed death-ligand 1 (PD-L1), providing a potential therapeutic target for these patients. Here we present data from the ovarian and uterine cancer cohorts of the Phase I atezolizumab monotherapy study (PCD4989g).

METHODS:

This Phase I, multi-center, first-in-human, open-label, dose-escalation/expansion clinical trial investigated single-agent atezolizumab in cohorts of patients with recurrent epithelial ovarian or uterine cancer. The primary objective was to evaluate the safety and tolerability of single-agent atezolizumab. Anti-tumor activity and preliminary assessment of potential biomarkers were evaluated as secondary and exploratory objectives, respectively.

RESULTS:

The ovarian and uterine cancer cohorts enrolled 12 and 15 patients, respectively (10 [83%] and 5 [33%], respectively, had PD-L1 ≥ 5% on tumor-infiltrating immune cells). Atezolizumab was generally well tolerated with no new safety signals identified. The safety profiles in both cohorts were consistent with the known profile of atezolizumab monotherapy. Treatment-related adverse events (AEs) were mostly Grade ≤ 2, with no treatment-related Grade ≥ 4 AEs reported. Preliminary anti-tumor activity, with long durations of response, was observed in 2 patients from each cohort (ovarian cancer, 8.1 and 30.6+ months; uterine cancer, 7.3 and 16.6+ months). High microsatellite instability and tumor mutational burden were noted in the responders from the uterine cancer cohort.

CONCLUSIONS:

Atezolizumab monotherapy was well tolerated in patients with epithelial ovarian or uterine cancer and may have clinical activity warranting further investigation.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier: NCT01375842.

KEYWORDS:

Atezolizumab; Epithelial ovarian cancer; Immune checkpoint inhibitor; Molecular markers; PD-L1; Uterine cancer

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