Background To determine the safety, preliminary efficacy, pharmacokinetics, and immunogenicity of a single cycle of RM-1929 photoimmunotherapy, an anti-EGFR antibody cetuximab conjugated with a light-activatable dye (IRDye®700DX), in Japanese patients with recurrent head and neck squamous cell carcinoma (rHNSCC). Methods Patients received a single fixed dose (640 mg/m2) of RM-1929 and a fixed light treatment dose (50 J/cm2 for superficial illumination; 100 J/cm fiber diffuser length for interstitial illumination). Safety, tumor response (modified RECIST v1.1 by central radiology review), pharmacokinetics, and immunogenicity were evaluated. Results Three Japanese patients were enrolled who had failed ≥ 3 prior lines of therapy including radiation, chemotherapy, cetuximab, and immunotherapy. Target lesions were: submental lesion; right superficial cervical node lesion and oropharynx lesion; and external auditory canal lesion. All patients experienced ≥ 1 treatment-emergent adverse event (TEAE), but none were considered dose-limiting. TEAEs were mild to moderate in severity except for one grade 3 application-site pain, which was transient, resolved without sequelae within 24 h, and did not affect study treatment administration. Thirteen of 17 TEAEs reported were possibly or probably related to study treatment. Three patient reports of application-site pain and localized edema were deemed probably related to study treatment. Objective response was observed in two patients (both partial responses). The third patient had disease progression. RM-1929 concentrations and pharmacokinetic parameters were similar in all patients. No patients tested positive for anti-drug antibodies. Conclusions RM-1929 photoimmunotherapy showed a manageable safety profile in rHNSCC. Tumor response in these heavily pre-treated patients was clinically meaningful and warrants further investigation. Clinical trial registration The trial was registered with the Japanese registry of clinical trials as jRCT2031200133.

Squamous cell carcinoma of the head and neck is characterized by an immunosuppressive environment and evades immune responses through multiple resistance mechanisms. A breakthrough in cancer immunotherapy employing immune checkpoint inhibitors has evolved into a number of clinical trials with antibodies against programmed cell death 1 (PD-1), its ligand PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) for patients with squamous cell carcinoma of the head and neck. CheckMate141 and KEYNOTE-048 were practice-changing randomized phase 3 trials for patients with platinum-refractory and platinum-sensitive recurrent or metastatic squamous cell carcinoma of the head and neck, respectively. Furthermore, many combination therapies using anti-CTLA-4 inhibitors, tyrosine kinase inhibitors and immune accelerators are currently under investigation. Thus, the treatment strategy of recurrent or metastatic squamous cell carcinoma of the head and neck is becoming more heterogeneous and complicated in the new era of individualized medicine. Ongoing trials are investigating immunotherapeutic approaches in the curative setting for locoregionally advanced disease. This review article summarizes knowledge of the role of the immune system in the development and progression of squamous cell carcinoma of the head and neck, and provides a comprehensive overview on the development of immunotherapeutic approaches in both recurrent/metastatic and locoregionally advanced diseases.

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Purpose: We sought to evaluate the efficacy and safety of the combination of cetuximab (Cmab) and paclitaxel (PTX) in patients with squamous cell carcinoma of the head and neck (SCCHN) who had unresectable recurrent or metastatic (R/M) disease after platinum-based chemoradiotherapy.Materials and Methods: Data on 23 patients with SCCHN who received paclitaxel and cetuximab (Cmab) for R/M disease no more than 6 months after CRT completion were retrospectively reviewed. PTX and Cmab were given in a 28-day cycle (PTX, 80 mg/m2 on days 1, 8, and 15; Cmab, loading dose 400 mg/m2 followed by a weekly 250 mg/m2). The differences in prognosis between subgroups in different clinical settings were also assessed.Results: CRT had been delivered as definitive treatment in 13 cases (57%) and as adjuvant treatment in 10 (43%). Median time from CRT completion to disease recurrence or metastasis was 73 days (1–152). The best objective response and disease control rates were 52 and 83%, respectively, with 12 partial responses and seven cases of stable disease by Response Evaluation Criteria in Solid Tumors (RECIST). A total of 17 of 23 patients (74%) achieved a degree of tumor shrinkage. Median progression-free survival (PFS) and overall survival (OS) were 7.0 (95% confidence interval [CI]: 3.7–8.4) and 16.3 months (95% CI: 7.8–23.3), respectively. Patients with a longer duration (≥60 d) from CRT completion to disease progression had a statistically significantly longer OS than the others (median OS 22.3 vs. 8.1 months, log-rank test; p = 0.034). Main Grade 3 toxicities included neutropenia (13%), anemia (13%), and hypomagnesemia (13%). No Grade 4 toxicity or treatment-related death was seen.Conclusion: PTX and Cmab is a tolerable and effective option in SCCHN patients with symptomatic CRT-refractory disease. Its favorable effects on tumor shrinkage will help relieve tumor-associated symptoms.

BackgroundWe investigated the tolerability of cetuximab plus radiotherapy in Japanese patients with untreated locally advanced squamous cell carcinoma of the head and neck.MethodsPatients with epidermal growth factor receptor-expressing locally advanced squamous cell carcinoma of the head and neck received cetuximab (400 mg/m2 initial dose then 250 mg/m2 weekly) for 7 weeks plus concomitant boost radiotherapy (weeks 2–7: once daily [1.8 Gy] for 3.6 weeks, then twice daily [1.8 Gy morning and 1.5 Gy afternoon] for 2.4 weeks). The primary endpoint was treatment completion rate (the rate of treated patients completing ≥70% of the planned cetuximab dose and the full dose of radiotherapy within 2 weeks over the planned schedule).ResultsTwenty-two patients were evaluable. The treatment completion rate was 100% (95% confidence interval 85–100). The response rate 8 weeks post-radiotherapy was 82% (95% confidence interval 60–95). The most common grade 3/4 treatment-emergent adverse events were mucosal inflammation (73%); dermatitis (27%); and infection, radiation skin injury and stomatitis (23% each).ConclusionsCetuximab plus concomitant boost radiotherapy can be safely administered to Japanese patients with locally advanced squamous cell carcinoma of the head and neck. Tolerability and efficacy were in line with those reported in the Phase III Bonner trial in a Western population of patients with locally advanced squamous cell carcinoma of the head and neck.