Combining bempegaldesleukin, pembrolizumab, and radiation therapy for treatment of head and neck squamous cell carcinoma.
Description
We report a phase II clinical trial (NCT04936841) evaluating combined palliative external beam radiotherapy, bempegaldesleukin (BEMPEG), and pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). In this single-arm study, we report 40% ORR and 4.2 months PFS in five patients treated prior to a decision by Nektar Therapeutics to stop further clinical investigation of BEMPEG. Upon two cycles of BEMPEG and pembrolizumab treatment, radiotherapy increased the effector:regulatory T-cell ratio and CD122+CD8+ T-cell infiltration in tumor biopsies. In preclinical HNSCC tumor models, 90Y-NM600 radiopharmaceutical therapy synergized with BEMPEG to promote an antitumor response and promoted increased tumor infiltration by CD122+CD8+ T cells. Both clinical and preclinical data showed increased PD-L1-expressing regulatory monocyte infiltration and, in preclinical models, combination therapy that included a PD-L1 inhibitor promoted the development of anti-tumor immune memory. This study suggests that a combination of radiotherapy, BEMPEG, and immune checkpoint blockade could be effective in HNSCC and identifies a novel effect of low-dose radiation in increasing CD122+CD8+ tumor-infiltrating T cells.