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

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 and Padmanee Sharma ()
Additional contact information
Matthew T. Campbell: The University of Texas MD Anderson
Surena F. Matin: The University of Texas MD Anderson Cancer Center
Alda L. Tam: The University of Texas of MD Anderson Cancer Center
Rahul A. Sheth: The University of Texas of MD Anderson Cancer Center
Kamran Ahrar: The University of Texas of MD Anderson Cancer Center
Rebecca S. Tidwell: The University of Texas MD Anderson Cancer Center
Priya Rao: The University of Texas MD Anderson Cancer Center
Jose A. Karam: The University of Texas MD Anderson Cancer Center
Christopher G. Wood: The University of Texas MD Anderson Cancer Center
Nizar M. Tannir: The University of Texas MD Anderson
Eric Jonasch: The University of Texas MD Anderson
Jianjun Gao: The University of Texas MD Anderson
Amado J. Zurita: The University of Texas MD Anderson
Amishi Y. Shah: The University of Texas MD Anderson
Sonali Jindal: The University of Texas MD Anderson Cancer Center
Fei Duan: The University of Texas MD Anderson Cancer Center
Sreyashi Basu: The University of Texas MD Anderson Cancer Center
Hong Chen: The University of Texas MD Anderson Cancer Center
Alexsandra B. Espejo: The University of Texas MD Anderson Cancer Center
James P. Allison: The University of Texas MD Anderson Cancer Center
Shalini S. Yadav: The University of Texas MD Anderson Cancer Center
Padmanee Sharma: The University of Texas MD Anderson

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26415-4

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