2391 - Phase I Study of Neoadjuvant Atezolizumab plus Concurrent SBRT in Borderline Resectable or Unresectable Cutaneous Squamous Cell Carcinoma: Preliminary Safety and Efficacy Results
Presenter(s)
K. Vo1, B. Modi2, J. Li3, T. Abuali1, S. Szeja4, S. Maroongroge5, E. Maghami6, T. Gernon6, K. Patel6, P. Malekzadeh7, K. Mahuron7, I. PAZ7, T. M. Williams1, and A. Amini5; 1City of Hope, Duarte, CA, 2Department of Dermatology, City of Hope National Medical Center, Duarte, CA, 3Division of Biostatistics, City of Hope National Medical Center, Duarte, CA, 4City of Hope, Upland, CA, 5Department of Radiation Oncology, City of Hope National Medical Center, Duarte, CA, 6Department of Surgery, City of Hope National Medical Center, Duarte, CA, 7City of Hope National Medical Center, Duarte, CA
Purpose/Objective(s): Borderline resectable and unresectable locally advanced cutaneous squamous cell carcinoma (cSCC) carries high risk of local recurrence and significant morbidity. Preclinical data show concurrent stereotactic body radiotherapy (SBRT) synergizes with programmed death-ligand 1 (PD-L1) blockade by preventing T-cell exhaustion critical for anti-tumor immunity. We hypothesized that concurrent atezolizumab plus SBRT would be safe and produce meaningful treatment response.
Materials/Methods:
This single-center, single-arm, phase I study (NCT0508549) enrolled patients with histologically confirmed borderline resectable/unresectable cSCC (head and neck/extremity), ECOG =2, and measurable disease per modified RECIST v1.1. Patients received atezolizumab 1200 mg IV on weeks 1,4, and 7 with concurrent SBRT (6-8 Gy × 5 fractions) to gross disease with cycle 1, starting at 40 Gy with de-escalation to 30 Gy for dose-limiting toxicities (DLTs). Elective nodal radiation was permitted to 25 Gy in 5 fractions. Surgery/repeat biopsies were performed at week 10 with PET/CT. Primary endpoints include safety and tolerability defined by DLTs per CTCAE v5.0. Secondary endpoints assessed clinical/pathologic response and disease control rate (DCR) at 3 months. Peripheral blood was collected at baseline, week 10, and 3 months for immune correlatives and circulating tumor DNA. Descriptive statistical analysis was performed for objective response rates per RECIST v1.1.Results:
Between April 2022–December 2025, 10 patients were enrolled; 8 were evaluable (1 deceased pre-treatment, 1 insufficient follow-up). Median follow-up was 8 months (range: 2-32). All patients received 40 Gy in 5 fractions, and no DLTs or treatment-related deaths occurred. Grade 1-2 toxicities included dermatitis (63%), fatigue, pain of skin, and dry mouth (38% each). One patient had grade 3 wound complication requiring surgical intervention. Of 8 evaluable patients, 5 patients underwent tissue evaluation (biopsy, n=2; surgery, n=3); 2 had clinical/radiographic complete responses (CR) with no residual lesion at week 10; one had partial response (PR) but unable to undergo tissue evaluation due to progressing comorbidities and subsequently passed away. Pathologic/clinical CR was observed in 4/5 (80%) patients with tissue evaluation. One patient had PR with 60% viable disease at surgery; complete resection was achieved and is patient remains disease-free at 32 months. All evaluable patients achieved disease control (DCR 100%) with no locoregional nodal recurrence, and none required additional therapy after treatment completion. Tissue and blood correlatives are currently being analyzed and will be reported subsequently.Conclusion:
Neoadjuvant atezolizumab plus concurrent SBRT showed promising clinical and pathologic complete response and disease-control rates in patients with locoregionally advanced cSCC with manageable low grade toxicity profile.