935PDPreliminary safety, efficacy, and PK/PD characterization from GARNET, a phase I clinical trial of the anti–PD-1 monoclonal antibody, TSR-042, in patients with recurrent or advanced MSI-H endometrial cancer

Background: TSR-042, a humanized monoclonal antibody, targets programmed death (PD)–1 effectively blocking interaction with its ligands PD-L1 and PD-L2. TSR-042 is being evaluated in patients with advanced solid tumors in the ongoing phase 1 GARNET trial (NCT02715284).1 We present safety and efficacy data from the microsatellite instability-high (MSI-H) endometrial cancer (EC) cohort, pharmacokinetics (PK) and receptor occupancy (RO) at the recommended phase 2 dose (RP2D), as well as biomarker analyses. Methods: Patients with previously treated MSI-H EC were evaluated. Patients received the RP2D of TSR-042: 500 mg Q3W for the first 4 cycles and 1000 mg Q6W thereafter. Antitumor activity was assessed by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Serum and peripheral blood mononuclear cells were collected for PK and RO measurements, respectively.1 Results: Twenty-five patients with MSI-H EC were enrolled and treated; median age was 66 years old and 56% had received prior therapy for metastatic/recurrent disease (median=1.0 line of treatment). Seventeen patients had at least 1 tumor assessment (week 12) and also underwent biomarker profiling. Partial responses (confirmed and unconfirmed) occurred in 9 patients (53%), 1 (6%) had stable disease, and 6 (35%) had progressive disease; one patient was not evaluable. Duration of response data for this cohort is not mature yet. Of the 25 patients, 18 (72%) had ≥1 adverse event (AE) with grade ≥3 AEs reported in 11 patients (44%). Treatment-emergent AEs (TEAEs) occurred in 18 patients (72%) with grade ≥3 TEAEs in 1 patient (4%) who experienced grade ≥3 leukopenia and grade ≥3 neutropenia. TSR-042 PK was dose-proportional. Maximal RO was observed at RP2D consistent with results in Parts 1 and 2A.1 Conclusions: TSR-042 demonstrated robust clinical activity in patients with previously treated recurrent or advanced MSI-H EC and an acceptable toxicity profile. PK was consistent across patients. Maximal RO was attained at RP2D. 1. Sachdev JC et al. Ann Oncol. 2017(suppl 5):28:420;1185P. Clinical trial identification: NCT02715284. Editorial acknowledgement: Editorial support, funded by Tesaro, Inc. (Waltham, MA, USA) and coordinated by Ted Paunescu, PhD of Tesaro, Inc., was provided by Dena McWain of Ashfield Healthcare Communications (Middletown, CT, USA). Legal entity responsible for the study: Tesaro, Inc. Funding: Tesaro, Inc. Disclosure: A. Oaknin: Advisory boards: Roche, AstraZeneca, PharmaMar, Clovis Oncology, Tesaro, Inc.; Support for travel or accommodation: Roche, AstraZeneca, PharmaMar. S.L. Ellard: Advisory boards: AstraZeneca, Astellas; Honoraria: AstraZeneca. C. Leath, III: Advisory boards: Mateon, Celsion. W. Guo, S. Lu, D. Jenkins, K. McEachern, K. Yu Jen, S. Dunlap, E. Im: Employment and stock and other ownership interests: Tesaro, Inc. L. Gilbert: Advisory boards: AstraZeneca, Roche. All other authors have declared no conflicts of interest.