Synapse - Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma

Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma Journal Article

Authors:	D'Angelo, S. P.; Richards, A. L.; Conley, A. P.; Woo, H. J.; Dickson, M. A.; Gounder, M.; Kelly, C.; Keohan, M. L.; Movva, S.; Thornton, K.; Rosenbaum, E.; Chi, P.; Nacev, B.; Chan, J. E.; Slotkin, E. K.; Kiesler, H.; Adamson, T.; Ling, L.; Rao, P.; Patel, S.; Livingston, J. A.; Singer, S.; Agaram, N. P.; Antonescu, C. R.; Koff, A.; Erinjeri, J. P.; Hwang, S.; Qin, L. X.; Donoghue, M. T. A.; Tap, W. D.
Article Title:	Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma
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. The activity of PD-1 blockade in patients with sarcoma has been modest so far. Here, the authors report the results of a pilot clinical trial to assess the efficacy and safety of bempegaldesleukin, a CD122-preferential interleukin-2 (IL-2) pathway agonist, in combination with the PD1 blockade (nivolumab) in patients with locally advanced or metastatic high-grade sarcoma.
Keywords:	prevalence; mutations; expression; soft-tissue sarcoma; tumor-infiltrating lymphocytes; sensitivity; hedgehog pathway; open-label; cancer; pd-1 blockade
Journal Title:	Nature Communications
Volume:	13
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Date Published:	2022-06-16
Start Page:	3477
Language:	English
ACCESSION:	WOS:000812995300019
DOI:	10.1038/s41467-022-30874-8
PROVIDER:	wos
PMCID:	PMC9203519
PUBMED:	35710741
Notes:	Article -- 3477 -- Source: Wos