PMID- 31204078 OWN - NLM STAT- MEDLINE DCOM- 20191014 LR - 20191210 IS - 1095-6859 (Electronic) IS - 0090-8258 (Linking) VI - 154 IP - 2 DP - 2019 Aug TI - Safety, clinical activity and biomarker assessments of atezolizumab from a Phase I study in advanced/recurrent ovarian and uterine cancers. PG - 314-322 LID - S0090-8258(19)31265-X [pii] LID - 10.1016/j.ygyno.2019.05.021 [doi] AB - 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 /= 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. CI - Copyright (c) 2019 Elsevier Inc. All rights reserved. FAU - Liu, Joyce F AU - Liu JF AD - Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215-5450, United States. Electronic address: Joyce_Liu@dfci.harvard.edu. FAU - Gordon, Michael AU - Gordon M AD - HonorHealth Research Institute, 10510 N 92nd St, Suite 200, Scottsdale, AZ 85258, United States. Electronic address: Michael.Gordon@HonorHealth.com. FAU - Veneris, Jennifer AU - Veneris J AD - University of Chicago Medicine, 5841 S Maryland Ave, Chicago, IL 60637, United States. Electronic address: Jennifer_Veneris@dfci.harvard.edu. FAU - Braiteh, Fadi AU - Braiteh F AD - Comprehensive Cancer Centers of Nevada, 3730 S Eastern Avenue, Las Vegas, NV 89169, United States. Electronic address: fadi.braiteh@usoncology.com. FAU - Balmanoukian, Ani AU - Balmanoukian A AD - The Angeles Clinic and Research Institute, 11818 Wilshire Blvd #200, Los Angeles, CA 90025, United States. Electronic address: abalmanoukian@theangelesclinic.org. FAU - Eder, Joseph Paul AU - Eder JP AD - Yale Cancer Center, Medical Oncology, PO Box 208028, New Haven, CT 06520-8028, United States. Electronic address: joseph.eder@yale.edu. FAU - Oaknin, Ana AU - Oaknin A AD - 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. FAU - Hamilton, Erika AU - Hamilton E AD - Tennessee Oncology/Sarah Cannon Research Institute, 250 25th Ave N, Nashville, TN 37203, United States. Electronic address: ehamilton@tnonc.com. FAU - Wang, Yulei AU - Wang Y AD - Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: wang.yulei@gene.com. FAU - Sarkar, Indrani AU - Sarkar I AD - Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: sarkar.indrani@gene.com. FAU - Molinero, Luciana AU - Molinero L AD - Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: molinero.luciana@gene.com. FAU - Fasso, Marcella AU - Fasso M AD - Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: fasso.marcella@gene.com. FAU - O'Hear, Carol AU - O'Hear C AD - Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: ohearc@gene.com. FAU - Lin, Yvonne G AU - Lin YG AD - Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, United States. Electronic address: lin-liu.yvonne@gene.com. FAU - Emens, Leisha A AU - Emens LA AD - UPMC Hillman Cancer Center, 300 Halket St, Suite 4628, Pittsburgh, PA 15213, United States. Electronic address: emensla@upmc.edu. LA - eng SI - ClinicalTrials.gov/NCT01375842 PT - Clinical Trial, Phase I PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20190614 PL - United States TA - Gynecol Oncol JT - Gynecologic oncology JID - 0365304 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents) RN - 0 (Biomarkers, Tumor) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 52CMI0WC3Y (atezolizumab) SB - IM MH - Adult MH - Aged MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Antibodies, Monoclonal, Humanized MH - Antineoplastic Agents/*administration & dosage/adverse effects MH - Biomarkers, Tumor MH - Carcinoma, Ovarian Epithelial/*drug therapy MH - Dose-Response Relationship, Drug MH - Female MH - Humans MH - Middle Aged MH - Neoplasm Recurrence, Local/*drug therapy MH - Ovarian Neoplasms/*drug therapy MH - Programmed Cell Death 1 Receptor MH - Uterine Neoplasms/*drug therapy MH - Young Adult OTO - NOTNLM OT - Atezolizumab OT - Epithelial ovarian cancer OT - Immune checkpoint inhibitor OT - Molecular markers OT - PD-L1 OT - Uterine cancer EDAT- 2019/06/18 06:00 MHDA- 2019/10/15 06:00 CRDT- 2019/06/18 06:00 PHST- 2019/03/22 00:00 [received] PHST- 2019/05/21 00:00 [revised] PHST- 2019/05/27 00:00 [accepted] PHST- 2019/06/18 06:00 [pubmed] PHST- 2019/10/15 06:00 [medline] PHST- 2019/06/18 06:00 [entrez] AID - S0090-8258(19)31265-X [pii] AID - 10.1016/j.ygyno.2019.05.021 [doi] PST - ppublish SO - Gynecol Oncol. 2019 Aug;154(2):314-322. doi: 10.1016/j.ygyno.2019.05.021. Epub 2019 Jun 14.