USG: study design, data interpretation and preparation of manuscript. further 25 patients (45%) had a relevant increase of intratumoral CD8+ cells (median increase by a factor of 3.0). Adverse event (AE) grade 3C4 appeared in 38 patients (68%) and mainly consisted of leukopenia (43%) and infections (29%). Six patients (11%) developed grade 3C4 immune-related AE. Univariate analysis computed p16 positivity, programmed death ligand 1 immune cell area and intratumoral CD8+ cell density as predictors of pCR. On multivariable analysis, intratumoral CD8+ cell density predicted pCR independently (OR 1.0012 per cell/mm2, 95% CI 1.0001 to 1 1.0022, p=0.016). In peripheral blood CD8+ cells, the coexpression of programmed death protein 1 significantly increased especially in patients with pCR. Conclusions Single cycle induction treatment with cisplatin/docetaxel and durvalumab/tremelimumab is usually feasible and achieves a high biopsy-proven pCR rate. strong class=”kwd-title” Keywords: radioimmunotherapy, head and neck neoplasms, CD8-Positive T-lymphocytes, clinical trials, Phase II as topic, combined modality therapy Introduction Immune checkpoint inhibitors directed against programmed death protein 1 (PD-1) have become standard treatment in patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC).1 2 A first phase Ib trial proved the feasibility of the PD-1 inhibitor pembrolizumab in combination with radiochemotherapy with weekly administration of cisplatin in locally advanced tumors.3 The ongoing phase III trials Keynote-412 and Javelin head and neck 100 add anti-PD(L)1 agents to standard radiochemotherapy with three administrations of high-dose Hoechst 33258 analog 2 cisplatin in locally advanced tumors. However, recently it was reported in a press release COG5 that Javelin head and neck 100 will not meet its primary endpoint. Beside primary radiochemotherapy, the strategy of induction chemotherapy followed by radio(chemo)therapy has become a treatment option for laryngeal cancer.4 However, when this strategy was expanded to other locations in the head and neck, randomized trials failed to Hoechst 33258 analog 2 prove a survival benefit compared with radiochemotherapy alone.5 In more recent trials using induction chemotherapy, excellent responders were identified after three cycles and subsequently treated with dose and volume-reduced radiotherapy in order to minimize late toxicity.6 7 The CheckRad-CD8 study was conducted to develop an efficient single cycle induction therapy, which allows patient selection for a further chemotherapy-free treatment based on pathologic response evaluation. Induction treatment consisted of cisplatin, docetaxel, durvalumab and tremelimumab. Patients with pathologic Hoechst 33258 analog 2 response joined definitive radiation therapy combined with durvalumab and tremelimumab followed by durvalumab maintenance, here called radioimmunotheapy. The combination of durvalumab with platinum-based chemotherapy was studied in the phase III CASPIAN trial in extensive-stage small cell lung cancer. In this trial, the addition of durvalumab increased overall survival (OS) without relevant increase in toxicity.8 The combination of durvalumab and tremelimumab with chemotherapy was studied in the Canadian phase IB IND226 trial mainly in patients with lung cancer. This was the first trial that proved the feasibility of a quadruple combination consisting of durvalumab and tremelimumab in combination with platinum-doublet chemotherapy and provided first dose recommendations.9 In this interim analysis of the CheckRad-CD8 trial the safety, antitumor activity and biological response of this single cycle induction treatment were studied in locally advanced HNSCC. To our knowledge, this is the first report on safety and antitumor activity of a combination scheme consisting of chemotherapy, programmed cell death ligand 1 (PD-L1) and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) antagonists. Material and methods Trial design and treatment CheckRad-CD8 is usually a multicenter open-label phase II study Hoechst 33258 analog 2 with a single treatment arm in patients with locally advanced HNSCC. Eligible patients received a single cycle of induction treatment in week 1 with cisplatin 30 mg/m2 body surface area (BSA) on days 1C3 and Hoechst 33258 analog 2 docetaxel 75 mg/m2 BSA on day 1. In patients with impaired renal function, cisplatin could be replaced by carboplatin.