Phase I study of RG7155, a novel anti-CSF1R antibody, in patients with advanced/metastatic solid tumors.

3005 Background: Tumor associated macrophages (TAM) suppress anti-tumor immunity and have been associated with poor prognosis in several types of cancer. CSF-1 is a critical survival and differentiation factor for TAM. Preclinically, TAM depletion has been shown to enhance/restore the activity of several clinically established treatment modalities and also novel immunotherapies. Here, we report on the phase I study of a monoclonal antibody (RG7155) that blocks the dimerization interface of the CSF1 receptor (CSF1R). Methods: In this dose-escalation and extension study, patients with advanced solid tumors or locally advanced pigmented villonodular synovitis (PVNS, a CSF1-driven "model disease" for clinical investigation of CSF1R targeting approaches) received RG7155 IV at dose levels between 100 – 3000mg Q2W. Primary objectives were to assess safety, tolerability, pharmaco-kinetics and –dynamics. Clinical activity was evaluated using FDG-PET (at 4 weeks after treatment start; EORTC criteria) and CT/MRI (every 6 weeks; RECIST 1.1). PD markers in pre- and on-treatment biopsies of tumor and surrogate skin tissue as well as peripheral blood were analyzed. Results: To date, data is available for 44 patients with solid tumors and 29 patients with PVNS. RG7155 treatment led to significant reduction of CSF1R+ and CD68/CD163+ macrophages in tumor and surrogate skin tissue and rapid elimination of CD14DimCD16Bright peripheral monocytes. In solid tumors, partial metabolic responses (FDG-PET) and disease stabilization were observed in 5/44 and 6/40 patients, respectively. 24/28 patients with PVNS experienced an objective response (best time point response). RG7155 was well tolerated. The MTD was not reached. Grade 3/4 AEs assessed as related to RG7155 were reported in 18% of patients (21/114). Most frequent AEs (any grade) were asthenia (70% of patients), peripheral edema (44%) and pyrexia (27%). Conclusions: RG7155 was well tolerated and biologically highly active. RG7155 is now being tested as a promising combination partner with immunotherapies (e.g. Phase Ib study (NCT02323191) in combination with Mab-PDL1 (MPDL3280A) is ongoing). Clinical trial information: NCT01494688.