Efficacy and Safety of Ultra-Low-Dose Immunotherapy in Relapsed Refractory Solid Tumors: Phase III Superiority Randomized Trial (DELII)

Clinical Snapshot

Key Findings

• P Value: P = 0.022

• Effect Size: Hazard ratio 0.80 (20% reduction in death risk)

• Primary Outcome: Median overall survival: 5.88 months (ultra-low nivolumab) vs 4.70 months (chemotherapy)

• Nnt Or Sensitivity: Number needed to treat approximately 10 patients to prevent one additional death at 1 year (based on 10.4% absolute survival difference)

• Confidence Interval: 95% CI 0.66 to 0.97

Clinical Application

Highly feasible - uses existing infrastructure, reduces drug costs substantially, and decreases toxicity burden Significant implications for PBS funding given potential 90% cost reduction while maintaining efficacy. May require TGA review of current nivolumab dosing recommendations. Aligns with COSA guidelines for palliative care focusing on quality of life Australian patients with advanced solid tumors who have progressed on standard therapy, particularly head and neck and lung cancers

Abstract

PURPOSE: Immune checkpoint inhibitors (ICIs) achieve sufficient receptor occupancy at much lower than standard approved doses. We hypothesized that ultra-low-dose nivolumab would retain clinical efficacy. PATIENTS AND METHODS: In this phase III randomized superiority trial, patients with advanced solid tumors (Eastern Cooperative Oncology Group 0-1) and progression on ≥1 prior line of systemic therapy were randomly assigned 1:1 to ultra-low-dose nivolumab (20 mg intravenously once every 2 weeks) or standard chemotherapy (docetaxel or paclitaxel, as per tumor type). Treatment continued until progression or intolerable toxicity. The primary end point was overall survival (OS). RESULTS: From June 2020 to February 2024, we enrolled 500 patients: 250 per arm; 52% had head and neck and 36% lung cancers. The median number of prior lines of therapy was 1 (range, 1-8); 29% had received ≥2 prior lines. Median OS was significantly longer with ultra-low-dose nivolumab: 5.88 months (95% CI, 4.99 to 7.13) versus 4.70 months (95% CI, 3.91 to 5.65; hazard ratio [HR], 0.80 [95% CI, 0.66 to 0.97]; P = .022). One-year OS was 27.3% versus 16.9%. Median progression-free survival was similar: 2.04 months (95% CI, 2.00 to 2.10) with ultra-low-dose nivolumab and 2.09 months (95% CI, 2.04 to 2.17) with chemotherapy (HR, 1.03 [95% CI, 0.86 to 1.23]; P = .77). Grade ≥3 treatment-related adverse events were less frequent with ultra-low-dose nivolumab (42.5% v 60.8%; P < .001). Quality of life (QoL) was significantly better with ultra-low-dose nivolumab. CONCLUSION: Ultra-low-dose nivolumab significantly improves OS versus chemotherapy in pretreated solid tumors, with fewer severe toxicities and better QoL. These findings support re-evaluation of ICI dosing strategies and may enhance global access.

References

1. 1.Noronha, V., Patil, V., Menon, N., Shah, M., Ostwal, V., Ramaswamy, A., Bhargava, P., Shah, S., Nawale, K., Shetake, A., Mathrudev, V., Sahu, L., Mehta, S., Deshmukh, C., Gaikwad, S., Chavan, S., Narayan, R., Ingale, R., Dhumal, S., Kaushal, R. K., Pai, T., Purandare, N., Janu, A., Chakrabarty, N., Sahu, A., Haria, P., Vaidyanathan, A., Trikha, M., Gedela, S., Banavali, S., Badwe, R. A., & Prabhash, K. (2026). Efficacy and safety of ultra-low-dose immunotherapy in relapsed refractory solid tumors: Phase III superiority randomized trial (DELII). Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-01546