1038 - Final Report of a Phase I/II Study of BMS-986156 (Glucocorticoid-Induced TNFR-Related Gene [GITR] Agonist) with Ipilimumab or Nivolumab with/without Stereotactic Ablative Radiotherapy in Patients with

X. Xu¹, J. W. Welsh¹, G. Shroff², N. I. Comeaux³, W. Li⁴, J. Rodon⁴, D. Karp⁴, E. E. Dumbrava⁴, A. B. Chen¹, D. S. Hong⁴, and J. Y. Chang¹; ¹Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ²Department of Thoracic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, ³Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁴Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX

Purpose/Objective(s): BMS-986156 is a fully human IgG1 agonist mAb that binds GITR and promotes T effector cell activation and possible inactivation of T regulatory cells. Combined anti-GITR, anti-PD-1, anti-CLTA-4 antibodies and radiotherapy improve tumor control in pre-clinical studies. Here we describe the final results of safety and therapeutic efficacy of BMS-986156 + Ipilimumab or Nivolumab with/without Stereotactic Ablative Radiotherapy (SABR) in patients with advanced solid cancers (NCT04021043). Materials/

Methods: This is an open-label, multi-group and pan-cancer phase 1/2 study conducted in a single center. Patients with histologically confirmed stage IV solid cancer who failed to standard treatments but eligible for immunotherapy and SABR were prospectively enrolled. Group 1 (n=20) received four cycles of Ipilimumab (3 mg/kg) plus BMS-986156 (30 or 100mg), Q3W. Group 2 (n=10) received four cycles of Ipilimumab (3 mg/kg) plus BMS-986156 (dose as determined in Group 1) ,Q3W with SABR (50Gy/4fx or 60-70Gy/10fx, targeted at 1-4 liver/lung lesions). Group 3 (n=20) received four cycles of Nivolumab (480mg) plus BMS-986156 (30mg), Q3W with SABR. Maintenance Nivolumab could be given up to two years. Tumor responses were assessed every three months until progression, using Immune Related Response Criteria (irRC). Global, in-radiation field and out-of-field responses were assessed separately.
Results: Fifty patients were enrolled between Oct 9, 2019 and Dec 14, 2021. Median follow-up was 32.3 (95%CI 8.6-56.0) months. Median overall survival was 8.3 (95%CI 4.3-12.3) months. Patients received a median of three (IQR 2–4.25) treatment cycles. 100 mg BMS-986156 with Ipilimumab was tolerated well. Five discontinued BMS-986156 with Ipilimumab due to treatment-related adverse events (TRAEs). Twenty-two patients (44%) experienced grade (G) 1-3 TRAEs. Six (12%) had G3 TRAES, with elevated alanine aminotransferase (n=3) and aspartate aminotransferase (n=2) being the most common. There were no G4/5 TRAEs. Thirty-nine patients were eligible for efficacy assessment with adequate follow-up imaging before salvage therapy due to rapid progression. Overall, nineteen (48.7%) had stable disease and three (7.7%) achieved partial response. Among 26 patients receiving SABR, only one had in-field recurrence (3.8%). Out-of-field (abscopal) disease control rate (ACR) and out-of-field (abscopal) response rate (ARR) were 38.5% and 7.7%, respectively, with highest ACR (50%, 9/18) and ARR (11.1%, 2/18) in group 3.
Conclusion: BMS-986156 was well-tolerated with Ipilimumab, Nivolumab, with or without SABR. Overall, more than half of patients had stable disease/partial response. The disease control rate and abscopal effect observed in those receiving SABR seem higher than reported in prior studies.