OPTIM: a randomized phase II trial of nivolumab followed by nivolumab-ipilimumab or docetaxel at progression in recurrent/metastatic squamous cell carcinoma of the head and neck (OPTIM; AIO-KHT-0117)

BACKGROUND: Treatment options after PD-1 inhibition for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN) remain limited. We investigated whether staggered immune checkpoint inhibition could improve outcomes compared with docetaxel in nivolumab-refractory disease. METHODS: In this randomized phase II trial, adults with platinum-refractory R/M-SCCHN received nivolumab and were randomized at progression to nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (NIVO-IPI) or docetaxel 75 mg/m² every 3 weeks (DOCE) until progression or intolerance. The primary endpoint was objective response rate (ORR) per RECIST 1.1; progression-free survival (PFS), overall survival (OS), and safety were secondary endpoints. PD-L1 expression was assessed in all patients. RESULTS: Among 14 patients in the NIVO-IPI arm and 17 in the DOCE arm, ORR was 0% versus 17.6%, median PFS was 1.97 versus 3.66 months (P = 0.036), and median OS was 3.97 versus 11.9 months (P = 0.356), respectively. Twelve-month OS rates were 28.6% and 44.6%. Outcomes were similar irrespective of PD-L1 status. Treatment-emergent adverse events occurred in 84.6% versus 81.3% of patients, with grade ≥3 events in 38.5% and 68.8%. CONCLUSIONS: NIVO-IPI did not improve efficacy over docetaxel and showed numerically inferior survival, whereas docetaxel was associated with greater toxicity. CLINICAL TRIAL REGISTRATION: EudraCT Nr. 2017-003349-14.