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 Gounder, Ciara Kelly, Mary Louise Keohan, Sujana Movva, Katherine Thornton, Evan Rosenbaum, Ping Chi, Benjamin Nacev, Jason E. Chan, Emily K. Slotkin, Hannah Kiesler, Travis 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 and William D. Tap
Additional contact information
Sandra P. D’Angelo: Memorial Sloan Kettering Cancer Center
Allison L. Richards: Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
Anthony P. Conley: The University of Texas MD Anderson Cancer Center
Hyung Jun Woo: Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
Mark A. Dickson: Memorial Sloan Kettering Cancer Center
Mrinal Gounder: Memorial Sloan Kettering Cancer Center
Ciara Kelly: Memorial Sloan Kettering Cancer Center
Mary Louise Keohan: Memorial Sloan Kettering Cancer Center
Sujana Movva: Memorial Sloan Kettering Cancer Center
Katherine Thornton: Memorial Sloan Kettering Cancer Center
Evan Rosenbaum: Memorial Sloan Kettering Cancer Center
Ping Chi: Memorial Sloan Kettering Cancer Center
Benjamin Nacev: Memorial Sloan Kettering Cancer Center
Jason E. Chan: Memorial Sloan Kettering Cancer Center
Emily K. Slotkin: Memorial Sloan Kettering Cancer Center
Hannah Kiesler: Memorial Sloan Kettering Cancer Center
Travis Adamson: Memorial Sloan Kettering Cancer Center
Lilan Ling: Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
Pavitra Rao: Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
Shreyaskumar Patel: The University of Texas MD Anderson Cancer Center
Jonathan A. Livingston: The University of Texas MD Anderson Cancer Center
Samuel Singer: Memorial Sloan Kettering Cancer Center
Narasimhan P. Agaram: Memorial Sloan Kettering Cancer Center
Cristina R. Antonescu: Memorial Sloan Kettering Cancer Center
Andrew Koff: Program in Molecular Biology, Memorial Sloan Kettering Cancer
Joseph P. Erinjeri: Memorial Sloan Kettering Cancer Center
Sinchun Hwang: Memorial Sloan Kettering Cancer Center
Li-Xuan Qin: Memorial Sloan Kettering Cancer Center
Mark T. A. Donoghue: Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
William D. Tap: Memorial Sloan Kettering Cancer Center

Nature Communications, 2022, vol. 13, issue 1, 1-11

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-30874-8

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