Investigators presented interim results from MOIO, an academic phase III randomized noninferiority trial, at the ESMO 2026 Congress in Madrid. The study evaluated whether reducing the frequency of immune checkpoint inhibitor (ICI) dosing to every three months, rather than continuing standard-dose intervals, could preserve efficacy in patients with locally advanced or metastatic solid tumors who had responded to at least six months of standard immunotherapy.
The trial did not meet its primary endpoint. Reduced-frequency ICI failed to demonstrate noninferiority for progression-free survival (PFS), with a hazard ratio (HR) that exceeded the prespecified noninferiority margin. Additionally, the reduced-frequency arm showed a statistically significant signal of worse overall survival (OS), raising concerns about the safety of a uniform de-escalation approach in this population.
Key finding
In the MOIO interim analysis, reducing ICI dosing frequency to every three months did not achieve noninferiority for PFS (HR 1.35; 95% CI 0.9–2.0) and was associated with a twofold higher risk of death (HR 2.0; 95% CI 1.1–3.9) compared with standard dosing, though the trial was stopped at an interim analysis and full enrollment was not completed.
Study Design
| Trial | MOIO — academic, multicentre, phase III randomized noninferiority trial; 36 French centers; NCT05078047 |
|---|---|
| Population | Adults with locally advanced or metastatic solid tumors in partial or complete response after ≥6 months of standard-dose ICI; melanoma patients in complete response were excluded |
| Treatment | Continued standard-dose ICI on standard schedule vs. reduced-frequency ICI at the same dose administered every 3 months; up to 646 patients planned for randomization |
| Primary endpoint | PFS; noninferiority margin defined as HR ≤1.3 |
| Key secondary endpoints | OS, duration of response (DOR), safety |
MOIO was designed with two interim futility analyses planned at 25% and 50% of 498 projected events, with a prespecified stopping rule if the one-sided p-value for HR=1 fell below 0.0192. The trial enrolled 340 patients between March 2022 and November 2025, and the second interim analysis, conducted at a median follow-up of 18.6 months in a modified intent-to-treat population of 308 patients, crossed the futility boundary, prompting early termination.
Results and Safety
For the primary endpoint, median PFS was 25 months (95% CI 19.4–not estimable) in the standard-dosing arm versus 21.9 months (95% CI 12.1–31.6) in the reduced-frequency arm (HR 1.35; 95% CI 0.9–2.0; p=0.0635). This HR exceeded the prespecified noninferiority margin of 1.3 and crossed the interim futility boundary, leading investigators to halt the trial. For OS, reduced-frequency ICI was associated with a significantly higher risk of death compared with standard dosing (HR 2.0; 95% CI 1.1–3.9; p=0.0143).
Exploratory analyses by tumor type revealed notable heterogeneity in the treatment effect. The HR for PFS was 2.9 (95% CI 1.3–6.7) in urothelial cancer and 1.6 (95% CI 0.8–3.1) in lung cancer, suggesting potential harm with de-escalation in these settings, whereas estimates in renal cell carcinoma (HR 0.7; 95% CI 0.3–1.5) and head and neck cancer (HR 0.6; 95% CI 0.1–2.4) were directionally favorable, though confidence intervals were wide and precluded firm conclusions. Patients treated beyond the first line showed a PFS HR of 2.9 (95% CI 0.9–4.9) with reduced-frequency dosing.
The safety profile did not demonstrate a meaningful advantage for the reduced-frequency strategy. Grades 3–4 immune-related adverse events occurred among 10.5% of patients in the standard arm and 9.5% in the reduced-frequency arm; serious adverse events were reported in 26.3% and 25.0%, respectively. Numerical differences were small, and no formal statistical comparisons of safety endpoints were reported in the abstract.
Clinical Context
Interest in ICI de-escalation strategies has grown alongside the expanding use of immunotherapy in advanced solid tumors, driven by goals of reducing cumulative toxicity, treatment burden, and cost, particularly for patients who have achieved durable responses. MOIO represents one of the more rigorous prospective attempts to test this concept in a broad, all-comer metastatic population. The trial’s early termination and survival signal add to the limited evidence base and suggest that a reduced dosing frequency among responders cannot be assumed to be a safe default across tumor types.
The investigators noted that heterogeneity in treatment effect across tumor type and line of therapy argues against a uniform de-escalation strategy, and called for biomarker-driven approaches to identify patients who may safely tolerate reduced ICI intensity. Key questions that remain unanswered include whether specific molecular or clinical subgroups could be prospectively identified as candidates for de-escalation, what the longer-term OS outcomes will look like as follow-up matures, and whether alternative de-escalation designs, such as treatment holidays or dose reductions rather than interval extensions, would yield different results.
Sources
- Gravis G, et al. MOIO: Interim analyses of a phase III randomized non inferiority trial assessing reduced frequency immune checkpoint inhibitors in responding patients with advanced/metastatic cancer. Abstract LBA10. Presented at ESMO 2026 Congress, Madrid, Spain.