Preliminary 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

Abstract

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. Method(s): 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 withMSI-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 notmature 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 Conclusion(s): TSR-042 demonstrated robust clinical activity in patients with previously treated recurrent or advanced MSI-HEC 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.