Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W. ClinicalTrials.gov ID: NCT02718911 (Registration Date: May 3, 2011).

Comprehensive Cancer Care Department Faculty of Medicine Masaryk Memorial Cancer Institute Brno Czech Republic

Department of Medical Oncology GZA Sint Augustinus Oosterveldlaan Wilrijk Belgium

Department of Medical Oncology Sarah Cannon Research Institute Tennessee Oncology Nashville TN USA

Department of Medicine Division of Hematology Oncology Columbia University College of Physicians and Surgeons New York NY USA

Department of Medicine Medical Oncology NYU Langone Health New York NY USA

Department of Oncology Clinical Research Institute at Rambam Rambam Medical Center Haifa Israel

Department of Oncology Sharett Institute of Oncology Hadassah Medical Center Jerusalem Israel

Department of Oncology University Antwerpen Universitair Ziekenhuis Antwerpen Drie Eikenstraat Edegem Belgium

Drug Development Unit Sarah Cannon Research Institute at HealthONE 1800 Williams St Ste 300 Denver CO USA

Drug Research Unit Universitair Ziekenhuis Gent Corneel Heymanslaan Ghent Belgium

Eli Lilly and Company Indianapolis IN USA

Eli Lilly and Company Windlesham Surrey UK

Hematologic Oncology Florida Cancer Specialists Sarah Cannon Research Institute Sarasota FL USA

Technion Israel Institute of Technology Haifa Israel

The Ella Institute for Immuno Oncology Sheba Medical Center Oncology Institute Tel Hashomer Ramat Gan Israel

The Faculty of Medicine The Wohl Institute for Translational Medicine Hadassah Medical Center Jerusalem Israel

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Targeting tumor-associated macrophages for successful immunotherapy of ovarian carcinoma

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ClinicalTrials.gov
NCT02718911