Background

We previously demonstrated, in a murine model, that localized radiotherapy and fms-like tyrosine kinase 3 (FLT3) ligand can act synergistically to control non-small cell lung cancer (NSCLC). Here we present preliminary results from an ongoing prospective clinical trial testing this combination in patients with advanced NSCLC.

Methods

Patients with advanced NSCLC that has previously been treated with at least one line of systemic therapy, at least two sites of active disease based on pre-treatment FDG-PET, and ECOG performance status 0-2 are eligible for this trial. Study subjects receive 5 daily subcutaneous injections of CDX-301 (75 µg/kg) concurrent with stereotactic body radiotherapy (SBRT) directed at a single intrathoracic site of disease. SBRT doses may range from 30 to 54 Gy, delivered over one week in 1, 3, or 5 fractions, depending on the target size and location. The primary study endpoint is survival without disease progression four months after treatment (PFS4). We hypothesize that the PFS4 rate will exceed 40%. Secondary endpoints include dose-limiting toxicities (grade ≥3 adverse events observed within 30 days of treatment and attributed to study therapy) and responses on PET based on total glycolytic activity (TGA), which is a volumetric measure of disease burden. Lesions targeted with SBRT are not included in radiographic response assessments. Based on PET Response Criteria in Solid Tumors (PERCIST) guidelines, a reduction in TGA of 45% or greater is classified as a partial response (PR).

Results

Nine subjects received study therapy between October 2016 and October 2017. Subjects were previously treated with a median of 2.5 courses of systemic therapy (range: 1-3). Seven subjects were previously treated with immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. No dose-limiting toxicities were observed. On PET performed two months after treatment, PR of lesions not targeted with SBRT (“abscopal effect”) was observed in 5/9 subjects. Responses were observed in unirradiated pulmonary, nodal, and osseous lesions. With a median follow-up duration of 5 months (range: 4 to 13 months), five subjects have developed disease progression, and two subjects have died. PFS4 was achieved in 5/9 subjects overall and in 5/5 subjects who demonstrated PR on PET. PR and PFS4 were achieved in 5/7 subjects who were previously treated with immunotherapy and in 0/2 subjects who were not previously treated with immunotherapy.

Conclusion

The combination of CDX-301 and stereotactic radiotherapy for advanced NSCLC has yielded promising early results, with frequent abscopal effects and a high PFS4 rate. This regimen may be particularly effective for patients who have previously been treated with immune checkpoint inhibitors targeting the PD-1/PD-L1 axis. Enrollment is ongoing to further characterize treatment efficacy and to explore the immunological effects of combining CDX-301 and SBRT.

Citation Format: Nitin Ohri, Balazs Halmos, Haiying Cheng, Tony Abraham, Tahir Yahya, Madhur Garg, William Bodner, Rafi Kabarriti, Shalom Kalnicki, Michael J. Yellin, Tibor Keler, Chandan Guha. FLT3 ligand (CDX-301) and stereotactic radiotherapy for advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT005.