Early interim results from a randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in non-small cell lung cancer (NSCLC)

Research output: Unpublished contribution to conferencePoster


Background: In preclinical models the combination of radiotherapy (RT, 3x8Gy) and immune checkpoint blockade (ICB) has shown to be synergistic. The presence of CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells (myDC) in the tumor microenvironment (TME) is a necessary prerequisite to induce an effector CD8+ T cell response and for response to ICB. Combining RT, ICB and intratumoral (IT) myDC administration has never been described before.
Brief methods: In this phase II clinical trial, oligoprogressive NSCLC patients progressing on PD-1 ICB (in monotherapy or combination therapy) were included. Patients underwent a leukapheresis followed by immunomagnetic bead isolation and cryopreservation of CD1c (BDCA-1)+ / CD141(BDCA-3)+ myDC. Progressive lesions were irradiated (3x8Gy over 5 days) followed by randomization (3:1) between immediate treatment arm (A) and a contemporary control arm (B). Patients in the immediate treatment arm received an IT injection of ipilimumab (10 mg) and avelumab (40 mg) into an accessible lesion in combination with intravenous (IV) administration of pembrolizumab (200 mg). The next day, all isolated myDC were injected in the same injected lesion. Patients continued to receive IT ipilimumab and avelumab with IV pembrolizumab q3w. For the contemporary control arm, IV pembrolizumab only was administered with a possibility of cross-over to intratumoral injections at progression. PET/CT was performed q12w. When safe, blood samples and tumor biopsies were collected at each treatment cycle.
Results: In this ongoing trial, at the cut-off date, 5 patients were enrolled (1 female), 4 in arm A and 1 in arm B. One patient crossed over from B to A. All but one patient were able to receive IT injection of myDC and ICB. Patients were on treatment for a median duration of 5.5 months (range 3-18). In patients that received at least 2 IT treatment administrations (incl myDC administration), a partial response was observed. Two patients were on treatment for 18 and 8 months, respectively. One patient died due to progressive disease. In one patient, IT treatment was not feasible due to rapid lesion regression after SBRT. There were no unexpected adverse events. One patient suffered a G3 pneumothorax. Translational research is ongoing (no conclusive results could be achieved yet due to low sample size) and includes cellular and molecular analysis.
IT injection of CD1c (BDCA-1)+ / CD141(BDCA-3)+ myDC in combination with repeated IT administration of ipilimumab and avelumab and systemic pembrolizumab has shown promising early results and no unexpected safety signals. It deserves further investigation in this ongoing trial.
Original languageEnglish
Publication statusPublished - 22 Sep 2022
EventImmunoRad: The International Conference on
Immunotherapy Radiotherapy Combinations
- New York, United States
Duration: 22 Sep 202224 Sep 2022


ConferenceImmunoRad: The International Conference on
Immunotherapy Radiotherapy Combinations
CountryUnited States
CityNew York
Internet address

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