Pembrolizumab in combination with bevacizumab and pegylated liposomal doxorubicin in patients with platinum-resistant epithelial ovarian cancer.

person Judith Michels Gustave Roussy Comprehensive Cancer Center, Villejuif, France info_outline Judith Michels, François Ghiringhelli, Jean-Sebastien Frenel, Caroline Brard, Benoit You, Anne Floquet, Lauriane Eberst, Rastilav Bahleda, Catherine Genestie, Corinne Balleyguier, Sophie Broutin, Patricia Pautier, Emeline Colomba, Fanny Pommeret, Christophe Massard, Aurelien Marabelle, Alexandra Leary

Authors person Judith Michels Gustave Roussy Comprehensive Cancer Center, Villejuif, France info_outline Judith Michels, François Ghiringhelli, Jean-Sebastien Frenel, Caroline Brard, Benoit You, Anne Floquet, Lauriane Eberst, Rastilav Bahleda, Catherine Genestie, Corinne Balleyguier, Sophie Broutin, Patricia Pautier, Emeline Colomba, Fanny Pommeret, Christophe Massard, Aurelien Marabelle, Alexandra Leary Organizations Gustave Roussy Comprehensive Cancer Center, Villejuif, France, Department of Medical Oncology, Center GF Leclerc, Dijon, France, GINECO & Institut de Cancerologie de l'Ouest, Centre René Gauducheau, Saint-Herblain, France, Gustave Roussy Cancer Center, University of Paris Sud, Villejuif, France, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, EMR UCBL/HCL 3738, Lyon, GINECO & GINEGEPS, Lyon, France, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens, Bordeaux, France, Institut de Cancérologie de Strasbourg Europe, Strasbourg, France, Institut Gustave Roussy, Villejuif, France, Gustave Roussy Cancer Center, INSERM U981, Villejuif, France, Gustave Roussy Cancer Campus, Villejuif, France, GINECO, French Sarcoma Group and Gustave Roussy Cancer Center, Villejuif, France, Gustave Roussy Cancerology Institute, Villejuif, Gineco Group, France, Gustave Roussy, Villejuif, France, Gustave Roussy-Department of Therapeutic Innovation and Early Trials (DITEP), Paris, France, Gustave Roussy Cancer Campus, Department of Drug Development (DITEP), Villejuif, France, Gustave Roussy Cancer Center, Villejuif, France Abstract Disclosures Research Funding Pharmaceutical/Biotech Company MSD, Other Foundation Background: There is a medical unmet need for effective treatments in platinum resistant ovarian cancer patients. We assessed the safety and efficacy of a combination of pembrolizumab with bevacizumab and pegylated liposomal doxorubicin (PLD). Methods: This is an open-label phase 1b trial in patients ECOG 0 or 1 with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. The safety of the dual combinations of pembrolizumab with bevacizumab or with PLD were previously evaluated in 6 patients respectively. In the absence of dose limiting toxicities (DLT) the triple combination was evaluated at a maximum tolerated dose (MTD)-1 for PLD in 3 patients and in the absence of DLT at MTD. The sample size was calculated according to the modified toxicity probability interval design. The primary evaluation criteria was the safety, the secondary endpoint was the outcome. Pharmacokinetics of the flat dose of bevacizumab will be evaluated. Results: 22 patients were enrolled from September 2019 until June 2020 in six French centers. 3 initial patients have been treated at 20mg/m 2 of PLD (MTD-1) and 19 patients were treated at the dose of 30mg/m 2 of PLD (MTD) combined with 200mg of pembrolizumab until progression, unacceptable toxicity, or withdrawal of consent and 400mg of bevacizumab for a total of six cycles. The patients’ characteristics are reported in the table. No DLT occurred. Grade 3 palmar-plantar erythrodysesthesia were reported in 4 patients. The recommended phase II dose of PLD was 30mg/m 2 in combination with pembrolizumab and bevacizumab. For patients treated at MTD, the overall response rate was 32% (6 partial responses) with 74% of clinical benefit with a durable response in 10 patients (53%). Median number of cycles was 7.5 (2 to not reached). Two patients are still on treatment. Correlative studies are ongoing. Conclusions: The combination was well tolerated and demonstrated clinical benefit in 74% platinum resistant ovarian cancer patients with durable response (>6 months) in 53% of patients. Clinical trial information: NCT03596281 Characteristics n (%) Age median range 70 47-77 Origin of cancer, ovary 22 (100) Histology at diagnosis Serous high grade Clear cell other 19 (86) 2 (9) 1 (5) BRCA mutations BRCA1 1 BRCA2 2 no 3 (14) 1 (5) 15 (68) Prior antiangiogenic therapy 18 (82) Prior treatment with PARP inhibitors 9 (41) Prior chemotherapy regimens 1-2 >2 12 (54) 9 (41) Platinum-free interval at first relapse <6 months 9 (41) 1 Two germline and one somatic, 2 One somatic., MSD, Other Foundation.