DELII Trial: Ultra-Low-Dose Nivolumab in Relapsed Refractory Solid Tumors
Noronha V, Patil V, Menon N, et al. Efficacy and Safety of Ultra-Low-Dose Immunotherapy in Relapsed Refractory Solid Tumors: Phase III Superiority Randomized Trial (DELII). Journal of Clinical Oncology 2026.
The Clinical Question
Immune checkpoint inhibitors cost approximately $5,000/month. The average Indian monthly income is $175 to $233. At Tata Memorial Hospital, only 2.8% of eligible patients could receive ICIs.
The pharmacology suggests much lower doses should work: efficacy requires a serum concentration of just 1.2 µg/mL, while standard dosing achieves approximately 33.7 µg/mL.
Can one-twelfth the standard dose of nivolumab still improve survival?
Study Design
Phase III superiority trial at Tata Memorial Hospital, Mumbai. 500 patients with relapsed solid tumors randomized 1:1 to ultra-low-dose nivolumab (20 mg IV q2w) vs standard chemotherapy. 52% head and neck cancer, 36% lung cancer. 77% PD-L1 positive.
Primary endpoint: Overall survival
Key Results
Overall Survival
Median OS | 5.88 months | 4.70 months |
1-Year OS | 27.3% | 16.9% |
HR (95% CI) | 0.80 (0.66-0.97) | — |
p-value | 0.022 | — |
20% reduction in death risk with one-twelfth the standard dose.
Progression-Free Survival
Median PFS | 2.04 months | 2.09 months |
HR (95% CI) | 1.03 (0.86-1.23) | — |
p-value | 0.77 | — |
OS benefit without PFS benefit, consistent with KEYNOTE-048 and CheckMate 057.
Safety and Quality of Life
Grade 3+ AEs | 60% | 42% |
QoL (global health) | — | Better (P = .014) |
Significantly fewer toxicities and better quality of life with immunotherapy.
Head and Neck Cancer Subgroup
The largest subgroup: 259 patients (52%). Buccal mucosa (29%) and oral tongue (13.6%) primaries.
HNC overall | 0.86 (0.67-1.11) | .247 |
Smokers | 0.62 | .004 |
Squamous histology | 0.78 | .038 |
Consistent benefit in HNC. Strong signal in smokers and squamous histology.
The Cost Equation
Nivolumab 20 mg: approximately $211/dose
Nivolumab 240 mg: $2,520/dose
55% of new cancer cases occur in Asia and Africa
70-80% of LMIC patients lack health insurance
For most patients worldwide, this cost difference determines access or no treatment.
Limitations
Single-center, open-label trial
Mixed tumor types, not powered for subgroup analyses
No PK/PD or biomarker studies
No comparison to standard-dose immunotherapy
Bottom Line
Ultra-low-dose nivolumab at one-twelfth the standard dose significantly improves overall survival — 20% reduction in death risk, fewer severe toxicities, better quality of life.
For HNC patients in resource-limited settings with no access to standard-dose ICIs, this could open the door to immunotherapy where none was previously available.
The unanswered question: how does ultra-low-dose compare to standard-dose? The authors call for evaluation earlier in treatment and in curative-intent settings.
Full Paper: https://doi.org/10.1200/JCO-25-01546
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Krishnakumar Thankappan
Head and Neck Oncology Journal Club