Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma
Sandra P. D’Angelo, Allison L. Richards, Anthony P. Conley, Hyung Jun Woo, Mark A. Dickson, Mrinal M. Gounder, Ciara M. Kelly, Mary Louise Keohan, Sujana Movva, Katherine A. Thornton, Evan Rosenbaum, Ping Chi, Benjamin A. Nacev, Jason E. Chan, Emily K. Slotkin, Hannah Kiesler, Travis E. Adamson, Lilan Ling, Pavitra Rao, Shreyaskumar Patel, Jonathan A. Livingston, Samuel Singer, Narasimhan P. Agaram, Cristina R. Antonescu, Andrew Koff, Joseph P. Erinjeri, Sinchun Hwang, Li‐Xuan Qin, Mark T.A. Donoghue, William D. Tap
Abstract
PD-1 blockade (nivolumab) efficacy remains modest for metastatic sarcoma. In this paper, we present an open-label, non-randomized, non-comparative pilot study of bempegaldesleukin, a CD122-preferential interleukin-2 pathway agonist, with nivolumab in refractory sarcoma at Memorial Sloan Kettering/MD Anderson Cancer Centers (NCT03282344). We report on the primary outcome of objective response rate (ORR) and secondary endpoints of toxicity, clinical benefit, progression-free survival, overall survival, and durations of response/treatment. In 84 patients in 9 histotype cohorts, all patients experienced ≥1 adverse event and treatment-related adverse event; 1 death was possibly treatment-related. ORR was highest in angiosarcoma (3/8) and undifferentiated pleomorphic sarcoma (2/10), meeting predefined endpoints. Results of our exploratory investigation of predictive biomarkers show: CD8 + T cell infiltrates and PD-1 expression correlate with improved ORR; upregulation of immune-related pathways correlate with improved efficacy; Hedgehog pathway expression correlate with resistance. Exploration of this combination in selected sarcomas, and of Hedgehog signaling as a predictive biomarker, warrants further study in larger cohorts.