Abstract 244: Abscopal responses in patients with refractory metastatic NSCLC treated with concurrent radiotherapy and CTLA-4 immune checkpoint blockade: evidence for the in situ vaccination hypothesis of radiotherapy

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background: The current median survival for patients with metastatic NSCLC is ∼7 mos. Novel approaches, such as immunotherapy, are warranted. Recent success with immune checkpoint blockade in metastatic NSCLC has been reported for blocking antibodies to PD-L1 and PD-1, but not to CTLA-4. We demonstrated pre-clinically that radiotherapy (RT) incites immunogenic cell death and enables cross-priming of tumor specific effector T-cells by DCs to eliminate in field and abscopal (ab-scopus, away from the target) metastases. We reported the 1st complete abscopal response in a patient with metastatic NSCLC, treated with RT and ipilimumab, who remains disease free >2.5 yrs. Thus, we initiated a prospective clinical trial (NYU S14-00208) to test this regimen in similar patients. We report the preliminary results on eight evaluable patients, who completed treatment. Methods: Eligible patients had chemo-resistant metastatic NSCLC, progressed on at least 1 chemotherapy regimen, ≥2 measurable lesions, ECOG PS ≤1, life expectancy >3 mos, non-steroid dependent, and no active intracranial disease. The first cohort consisted of patients treated with 6Gy x5 plus ipilimumab (3mg/kg x4 cycles). Patients were evaluated with pre and post-treatment (day 81 from treatment inception) PET/CTs. Results: Eight patients treated are currently evaluable (Table). The median prior chemotherapy regimens was 2, prior RT courses was 1.5, and time from diagnosis of metastatic disease was 6.75 mos. Conclusion: Metastatic NSCLC is only marginally responsive to CTLA-4 blockade alone; yet, our preliminary data suggest that with the addition of RT, objective responses are more common. This novel approach to treating metastatic NSCLC holds tremendous promise. The trial continues the planned accrual of 29 patients. | # | Time from Metastatic Disease (Mos) | # of Prior Treatments | Irradiated Site | irRECIST PET/CT | Best Abscopal Response | Maximum Toxicity | |:-- | ---------------------------------- | --------------------- | ---------------------------------------- | --------------- | -------------------------- | ---------------- | | 1 | 4.3 | 3 chemo | L para-spinal mass | SD (-37.5%) | L hilar lymph node | G2 fatige | | | | 2 RT | | | PR (-68%) | | | 2 | 38.5 | 4 chemo | L fissural nodule | SD (+7.2%) | L diaphragmatic lymph node | G2 rash | | | | 3 RT | | | SD (-16.7%) | | | 3 | 0.9 | 2 chemo | R anterior pleural nodule | CR (-100%) | R pleural nodule | G2 rash | | | | 2 RT | | | CR (-100%) | | | 4 | 3.5 | 1 chemo | R hilum | CR (-100%) | L Sclav lymph node | G3 (ALT) | | | | 1 RT | | | CR (-100%) | | | 5 | 7 | 1 chemo | R upper lobe nodule | POD (+57%) | R Sclav lymph node | G1 pruritis | | | | | | | SD (+10%) | | | 9 | 18.4 | 2 chemo | Porta hepatis lymph nodes | SD (+15%) | Peripancreatic lymph node | G1 fatigue | | | | 2 RT | | | PR (-65%) | | | 10 | 16 | 2 chemo | R lower lobe, posterior to the hilum | POD (+47.9%) | R peri-hilar lymph node | G2 pruritis | | | | | | | SD (+10%) | | | 11 | 6.5 | 1 chemo | Posterior L lower lobe subpleural nodule | POD (+479%) | Medial L lung base | G2 dyspnea | | | | | | | SD (-6.25%) | | Table: CR = complete response, PR = partial response, SD = stable disease, POD = progression of disease Citation Format: Encouse B. Golden, Abraham Chachoua, Maria Fenton-Kerimian, Sandra Demaria, Silvia C. Formenti. Abscopal responses in patients with refractory metastatic NSCLC treated with concurrent radiotherapy and CTLA-4 immune checkpoint blockade: evidence for the in situ vaccination hypothesis of radiotherapy . [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 244. doi:10.1158/1538-7445.AM2015-244