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 solid tumors

Background Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1) + /CD141(BDCA-3) + myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. Methods In this phase II clinical trial, anti-PD-...

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Published in:Cancer Immunology, Immunotherapy : CII Immunotherapy : CII, 2024-07, Vol.73 (9), p.167, Article 167
Main Authors: Vounckx, Manon, Tijtgat, Jens, Stevens, Latoya, Dirven, Iris, Ilsen, Bart, Vandenbroucke, Frederik, Raeymaeckers, Steven, Vekens, Karolien, Forsyth, Ramses, Geeraerts, Xenia, Van Riet, Ivan, Schwarze, Julia Katharina, Tuyaerts, Sandra, Decoster, Lore, De Ridder, Mark, Dufait, Ines, Neyns, Bart
Format: Article
Language:English
Subjects:
Cancer Research
CD1c antigen
Clinical trials
Dendritic cells
Effector cells
Immune checkpoint inhibitors
Immunology
Leukapheresis
Lymphocytes T
Medicine
Medicine & Public Health
Melanoma
Metastasis
NCT
NCT04571632
Non-small cell lung carcinoma
Oncology
Patients
PD-1 protein
Pembrolizumab
Pneumothorax
Radiation therapy
Response rates
Small cell lung carcinoma
Solid tumors
Tumor microenvironment
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Summary:Background Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1) + /CD141(BDCA-3) + myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB. Methods In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1) + /CD141(BDCA-3) + myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS). Results Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event. Conclusion SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint. Trial registration number : Clinicaltrials.gov: NCT04571632 (09 AUG 2020). EUDRACT: 2019-003668-32. Date of registration : 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.
ISSN:1432-0851
0340-7004
1432-0851
DOI:10.1007/s00262-024-03751-0