275 - FLT3 Ligand (CDX-301) and Stereotactic Radiotherapy for Advanced Non-Small Cell Lung Cancer

12:50pm - 01:00pm ET

Room 156

Presenter(s)

Nitin Ohri, MD, MS - Albert Einstein College of Medicine, Bronx, NY

N. Ohri¹, B. Halmos¹, M. K. Garg², J. Levsky¹, H. Cheng¹, R. Gucalp¹, W. R. Bodner III¹, R. Kabarriti², T. Keler³, S. Kalnicki¹, and C. Guha¹; ¹Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, ²Department of Radiation Oncology, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, ³Celldex Therapeutics, Hampton, NJ

Purpose/Objective(s):

In a murine non–small cell lung cancer (NSCLC) model, we previously demonstrated synergy between localized radiotherapy and the dendritic cell growth factor fms-like tyrosine kinase 3 (FLT3) ligand. We now report long-term results from a phase II clinical trial evaluating this combination in patients with advanced NSCLC.

Materials/Methods:

Patients with advanced NSCLC and multifocal active disease after at least one line of systemic therapy received five daily subcutaneous injections of the FLT3 ligand CDX-301 (75 µg/kg) administered concurrently with stereotactic body radiotherapy (SBRT) to a single disease site. SBRT was delivered with a dose of 30–54 Gy in 1–5 fractions, based on target size and location. PET/CT imaging was performed at baseline and every two months for one year. Serial blood samples were collected for analyses of immune activation. Additional “cycles” of SBRT and CDX-301 could be administered at least four months after initial treatment, at the discretion of the treating physicians. The primary endpoint was progression-free survival at four months (PFS4), with the hypothesis that the PFS4 rate would exceed 40%. Secondary endpoints included overall survival (OS), PET response (PERCIST criteria), CT response (RECIST criteria), and dose-limiting toxicities (grade =3 adverse events within 30 days). Lesions treated with SBRT were excluded from response assessments. The planned sample size was 29 patients.

Results:

Twenty-nine patients received study therapy between October 2016 and January 2020. Participants had received a median of three prior lines of systemic therapy (range, 1–5), including PD-1/PD-L1 checkpoint inhibitors in 26 patients (90%). No dose-limiting toxicities were observed. Correlative immune analyses will be presented at the meeting. The PFS4 rate was 55%, meeting the pre-specified efficacy objective. With a median follow-up of 6.5 years among surviving patients, median OS was 18 months. Partial responses of lesions not treated with SBRT (“abscopal responses”) were observed in 9 patients (31%) using PET criteria and in 4 patients (14%) using CT criteria. Seven patients (24%) received a second course of SBRT and CDX-301. Only eight patients (28%) received additional systemic therapy after study treatment. Exploratory analyses suggest improved outcomes among patients with limited disease burden at study entry: median OS was 29 months for the 16 patients with 2–4 active lesions, compared with 6 months for the 13 patients with =5 active lesions (log-rank p = 0.020).

Conclusion:

CDX-301 combined with SBRT is well tolerated and demonstrates systemic activity in advanced NSCLC. Additional trials evaluating this in situ vaccination strategy are planned.