TY - JOUR
T1 - Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma
AU - D’Angelo, Sandra P.
AU - Richards, Allison L.
AU - Conley, Anthony P.
AU - Woo, Hyung Jun
AU - Dickson, Mark A.
AU - Gounder, Mrinal
AU - Kelly, Ciara
AU - Keohan, Mary Louise
AU - Movva, Sujana
AU - Thornton, Katherine
AU - Rosenbaum, Evan
AU - Chi, Ping
AU - Nacev, Benjamin
AU - Chan, Jason E.
AU - Slotkin, Emily K.
AU - Kiesler, Hannah
AU - Adamson, Travis
AU - Ling, Lilan
AU - Rao, Pavitra
AU - Patel, Shreyaskumar
AU - Livingston, Jonathan A.
AU - Singer, Samuel
AU - Agaram, Narasimhan P.
AU - Antonescu, Cristina R.
AU - Koff, Andrew
AU - Erinjeri, Joseph P.
AU - Hwang, Sinchun
AU - Qin, Li Xuan
AU - Donoghue, Mark T.A.
AU - Tap, William D.
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-022-30874-8
DO - 10.1038/s41467-022-30874-8
M3 - Article
C2 - 35710741
AN - SCOPUS:85132275841
SN - 2041-1723
VL - 13
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 3477
ER -