Phase 3 trial of efficacy and safety of ultra-low-dose immunotherapy for relapsed or refractory solid tumors

Immune checkpoint inhibitors (ICIs) achieve sufficient receptor occupancy at lower than standard approved doses. The phase 3 DELII trial, at Tata Memorial Hospital (Mumbay, India) evaluated ultra-low dose (ULD) nivolumab (20 mg intraveneously once every 2 weeks) for patients with advanced solid tumors, with ECOG performance status 0 or 1 and progression on at least one prior line of systemic therapy. Patients were randomized 1:1 to ULD nivolumab (n=250) or standard chemotherapy (docetaxel or paclitaxel, as per tumor type; n=250). Most patients had head and neck cancer (52%) or lung cancer (36%). The median number of prior lines of therapy was 1 (range 1-8); 29% had received 2 or more prior lines. The primary endpoint was overall survival (OS). Median OS was significantly longer with ULD nivolumab compared with chemotherapy: 5.88 months versus 4.70 months HR 0.80; p=0.022) with one-year OS 27.3% versus 16.9%. Median progression-free survival was similar in the two groups: 2.04 months versus 2.09 months (HR 1.03; p=0.77). Grade ≥ 3 treatment-related adverse events were less frequent with ULD nivolumab (42.5% versus 60.8%; p<0.001), whereas quality of life was significantly better with ULD nivolumab. The authors conclude that ULD nivolumab significantly improves OS versus chemotherapy in pretreated solid tumors, with fewer severe toxicity and better quality of life.