Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2026
A Phase II Study of Stereotactic Ablative Radiotherapy plus Atezolizumab plus Tiragolumab in Treatment-Naïve Patients with Advanced Non-Small Cell Lung Cancer.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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10 authors.
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Abstract
purposeSKYROCKET is a single-center, single-arm phase II study that evaluated whether the addition of stereotactic body radiotherapy (SBRT) to atezolizumab plus tiragolumab enhances antitumor efficacy in PD-L1-positive non-small cell lung cancer (NSCLC). PATIENTS AND
methodsPatients received SBRT to all metastatic sites and subsequently received atezolizumab and tiragolumab every 3 weeks on day 1 of each 21-day cycle with 7 days of completion of SBRT. The primary endpoint was investigator-assessed progression-free survival (PFS) from the start of SBRT. Exploratory endpoints included single-cell RNA sequencing (scRNA-seq) obtained from tumor biopsies at baseline (BL) and on-treatment (OT) and were further characterized as clinical benefit [CB; partial response or stable disease (SD) ≥ 6 months] and non-clinical benefit (NCB; progressive disease or SD < 6 months).
resultsForty-one patients were enrolled. At a median duration of follow-up of 9.8 months, median PFS at the start of SBRT was 9.3 months [95% confidence interval (CI), 6.0-NR]. No new safety signal was observed. scRNA-seq of paired BL and OT (n = 3) and single-time point (n = 2) revealed that CD8 progenitor-exhausted (TPEX) cells markedly expanded after treatment, with high T-cell immunoreceptor with Ig and ITIM (TIGIT) and PD-1 expression in CD8 TPEX/TEX subsets. CD4 regulatory T cells (Treg) were reduced in the CB group but increased in the NCB group. The CB group showed reduced Treg suppression and NECTIN-TIGIT signaling, whereas NCB maintained proliferative CTLA4high/TIGIThigh Treg supported by ICAM/galectin-CTLA4 pathways.
conclusionsSBRT followed by atezolizumab plus tiragolumab showed encouraging clinical activity with manageable safety in PD-L1-positive metastatic NSCLC.
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