A phase II study of cryoablation (cryo) of an enlarging tumor in patients (pts) with advanced lung cancer or melanoma receiving post-progression immune checkpoint inhibition (ICI).

Abstract

e14243 Background: Image-guided percutaneous cryoablation is an established minimally invasive oncologic treatment. Through direct modulation of the tumor, it is theorized that this local therapy may modify the immune microenvironment. We hypothesized that it can augment an anti-tumor response when used concurrently with ICI. Methods: In this phase II single-arm study, pts with advanced lung cancer or melanoma progressing on ICI undergo cryo of an enlarging lesion and ICI is continued for a minimum 2 additional cycles. Computed tomography is performed at 4-6 weeks following cryo to determine tumor response in non-ablated lesions per RECIST1.1, with confirmatory scans at 8-10 weeks. The primary endpoint is safety and feasibility. Secondary endpoints are overall response rate (ORR) and disease control rate (DCR) with DCR defined as the percentage of pts who achieve complete response (CR), partial response (PR), and stable disease (SD). Correlative analysis on pre- and post-cryo biopsy specimen, when evaluable, will be performed. A planned analysis to document preliminary safety and feasibility in the first 11 patients was performed. Results: 11 pts (out of planned 40) have been enrolled. 8 with melanoma, 3 with lung cancer. All pts received prior PD-1/PD-L1 monotherapy with 8 pts treated with pembrolizumab, 2 with nivolumab and 1 with atezolizumab. Treated lesions were in lung (n = 4), bone (n = 3), lymph nodes (n = 2), liver (n = 1) and adrenal gland (n = 1). No immune related adverse events occurred. There was one treatment-related CTCAE grade 3 event (osteomyelitis) but no grade 4/5 events. One pt. experienced grade 3 hyponatremia, unrelated to cryo. In evaluable pts (n = 10), ORR was 10% and DCR was 50% (4 SD, 1 PR). Conclusions: During this scheduled safety analysis, cryo following progression on ICI was feasible and had an acceptable side effect profile. Early efficacy data of this potentially synergistic approach is encouraging but warrants further investigation. Clinical trial information: NCT03290677. [Table: see text]