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SIR 2026

Scientific Session

Interventional Oncology

Session: IO - Ablation Science

338 - Phase I Trial of Cryoablation and Immunotherapy in Patients with Adaptive Immunotherapy Resistance, the CEDAR Trial: Cryoablation Challenge Evaluated in Adaptive-Immune Resistance

Wednesday, April 15, 2026
11:42 AM - 11:51 AM ET
Purpose: We hypothesized that cryoablation performed in metastatic cancer patients, who have previously responded to immunotherapy but who now have disease progression, will be safe and re-initiate an immunological response in the setting of continued standard of care immunotherapy. The primary endpoint was best objective response by iRECIST within 12 months of cryoablation.

Materials and Methods: This study is an open-label, single center trial that enrolled patients with adaptive immunotherapy resistance (prior response to PD1/PD-L1 based therapy followed by progression as defined by RECIST 1.1). Cryoablation and pre- and post-treatment biopsies were performed. Tumor response was assessed by iRECIST. Correlative studies were performed on tumor tissue and peripheral blood.

Results: Fifteen metastatic solid tumor patients with adaptive immunotherapy resistance were consented and fourteen patients were treated with cryoablation and immunotherapy (5 pembrolizumab, 5 nivolumab, 2 nivolumab + ipilimumab, 1 avelumab, 1 atezolizumab). Twelve patients were evaluable for efficacy (8 RCC, 1 esophageal, 1 melanoma, 1 urothelial, 1 peritoneal mesothelioma). Cryoablation was successful with no post-procedural complications. The best overall response was: 58.3% (7/12) iSD, and 41.7% (5/12) iPD. Median PFS and median OS were 7.3 months and 31.9 months. Paired tumor tissue demonstrated a paucity of viable tissue with limited changes in immune cell populations by Nanostring. Peripheral blood flow cytometry analysis demonstrated similar immune populations in pre- and post-cryoablation samples and no upregulation in the expression of inhibitory or activation markers was evident. Pre- and post-cryoablation single-cell RNA sequencing of the subset of metastatic RCC patients revealed a largely inactive immune environment with T-cell dysfunction and lack of checkpoint receptor expression.

Conclusion: Cryoablation combined with immunotherapy failed to reverse T-cell dysfunction in metastatic cancer patients who have developed adaptive resistance to prior immunotherapy.