Pilot study of Tremelimumab with and without cryoablation in patients with metastatic renal cell carcinoma View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-11-04

AUTHORS

Matthew T. Campbell, Surena F. Matin, Alda L. Tam, Rahul A. Sheth, Kamran Ahrar, Rebecca S. Tidwell, Priya Rao, Jose A. Karam, Christopher G. Wood, Nizar M. Tannir, Eric Jonasch, Jianjun Gao, Amado J. Zurita, Amishi Y. Shah, Sonali Jindal, Fei Duan, Sreyashi Basu, Hong Chen, Alexsandra B. Espejo, James P. Allison, Shalini S. Yadav, Padmanee Sharma

ABSTRACT

Cryoablation in combination with immune checkpoint therapy was previously reported to improve anti-tumor immune responses in pre-clinical studies. Here we report a pilot study of anti-CTLA-4 (tremelimumab) with (n = 15) or without (n = 14) cryoablation in patients with metastatic renal cell carcinoma (NCT02626130), 18 patients with clear cell and 11 patients with non-clear cell histologies. The primary endpoint is safety, secondary endpoints include objective response rate, progression-free survival, and immune monitoring studies. Safety data indicate ≥ grade 3 treatment-related adverse events in 16 of 29 patients (55%) including 6 diarrhea/colitis, 3 hepatitis, 1 pneumonitis, and 1 glomerulonephritis. Toxicity leading to treatment discontinuation occurs in 5 patients in each arm. 3 patients with clear cell histology experience durable responses. One patient in the tremelimumab arm experiences an objective response, the median progression-free survival for all patients is 3.3 months (95% CI: 2.0, 5.3 months). Exploratory immune monitoring analysis of baseline and post-treatment tumor tissue samples shows that treatment increases immune cell infiltration and tertiary lymphoid structures in clear cell but not in non-clear cell. In clear cell, cryoablation plus tremelimumab leads to a significant increase in immune cell infiltration. These data highlight that treatment with tremelimumab plus cryotherapy is feasible and modulates the immune microenvironment in patients with metastatic clear cell histology. More... »

PAGES

6375

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-021-26415-4

DOI

http://dx.doi.org/10.1038/s41467-021-26415-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1142390888

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/34737281


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