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- Title
Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma.
- Authors
D'Angelo, Sandra P.; Richards, Allison L.; Conley, Anthony P.; Woo, Hyung Jun; Dickson, Mark A.; Gounder, Mrinal; Kelly, Ciara; Keohan, Mary Louise; Movva, Sujana; Thornton, Katherine; Rosenbaum, Evan; Chi, Ping; Nacev, Benjamin; Chan, Jason E.; Slotkin, Emily K.; Kiesler, Hannah; Adamson, Travis; Ling, Lilan; Rao, Pavitra; Patel, Shreyaskumar
- 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.
- Subjects
HEDGEHOG signaling proteins; NIVOLUMAB; SARCOMA; NOMOGRAPHY (Mathematics); ISOLATION perfusion; ADVERSE health care events; PILOT projects
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-30874-8