245 - Phase I Dose Escalation/Dose Expansion Trial of NBTXR3/SBRT in Combination with Nivolumab or Pembrolizumab for the Treatment of anti-PD-1 Naïve or Resistant Patients with Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Presenter(s)
C. Shen1, A. Sukari2, W. A. Stokes3, G. Q. Yang4, N. F. Saba5, J. Weiss6, J. M. Frakes7, J. J. Caudell4, P. Chang8, S. Murgu9, M. Lohr10, J. W. Chan11, K. Kirtane12, D. Rolando13, O. I. Vivar13, Z. Gooi14, A. Juloori15, T. Hackman16, and A. J. Rosenberg17; 1Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, 2Karmanos Cancer Institute, Detroit, MI, 3Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, 4H. Lee Moffitt Cancer Center and Research Institute, Department of Radiation Oncology, Tampa, FL, 5Emory University, Atlanta, GA, 6University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 7Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 8University of Chicago, Chicago, IL, 9UChicago Medicine, Chicago, IL, 10Sanford Health, Sioux Falls, SD, United States, 11Department of Radiation Oncology, University of California San Francisco, San Francisco, CA, 12H. Lee Moffitt Cancer Center, Tampa, FL, 13Nanobiotix, Paris, France, 14Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of Chicago, Chicago, IL, 15Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, 16Department of Otolaryngology, University of North Carolina School of Medicine, Chapel Hill, NC, 17Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL
Purpose/Objective(s): Immune checkpoint inhibitors (ICIs) alone or in combination with chemotherapy are now a standard of care in recurrent/metastatic (R/M) HNSCC, but their efficacy is limited. While locoregional recurrence is the most clinically significant pattern of failure for both morbidity and mortality, distant failure also contributes meaningfully to outcomes in this patient population. As such, optimizing control of one or both addresses unmet needs. NBTXR3 is a novel radioenhancer composed of functionalized hafnium oxide nanoparticles administered by a single intratumoral injection which locally amplifies radiotherapy (RT). NBTXR3/RT has also demonstrated an ability to trigger local and systemic immune responses in pre-clinical models. Here we report outcomes in patients with R/M HNSCC who were either naïve to or continued ICI therapy combined with NBTRX3/RT after primary or secondary resistance to ICI alone.
Materials/Methods: In a phase I dose escalation and expansion trial [NCT03589339] evaluating NBTXR3/RT followed by nivolumab or pembrolizumab, two cohorts of patients with locoregionally recurrent or metastatic HNSCC naïve or resistant to prior ICI were treated. Patients had H&N lesions, lung, liver, or soft tissue metastases. Stereotactic body RT (SBRT) doses and techniques were delivered: H&N 35 Gy in 5 fractions; lung 45 Gy in 5 fractions; liver 45 Gy in 3 fractions. Primary objective was safety and establishing the RP2D of NBTXR3/RT/anti-PD-1 combination. Secondary objectives include efficacy.
Results: 89 patients were treated: 39 ICI naïve, 50 ICI resistant with median age of 64 years, 57% ECOG 1, and 48% HPV negative. NBTXR3 injection was feasible with an acceptable safety profile. There were 15 patients (16.9%) who experienced G=3 treatment emergent adverse events (TEAEs), of whom 4 patients (4.5%) experienced G=3 NBTXR3-related TEAEs. One patient had a Grade 5 DLT (pneumonitis) after receiving RT to the neck while receiving ICI. The RP2D was 33%. 30 ICI-naïve and 38 ICI-resistant patients were evaluable for efficacy. In ICI naïve, the objective response rate was 46.7% (14/30) and disease control rate was 73.3% (22/30). In ICI resistant, the objective response rate was 28.9% (11/38) and disease control rate was 65.8% (25/38). There were observed responses in injected lesions as well as in some non-injected target lesions. Survival outcomes in naïve and resistant patients will be presented.
Conclusion: Use of NBTXR3 when combined with SBRT and anti PD-1 was both feasible and well tolerated in patients with R/M HNSCC. These data compare favorably to historical controls and merit further investigation in randomized trials in this population.