Clinical Summary: 

• Design/Population: The phase 3 MOIO trial evaluated standard-frequency versus reduced-frequency immune checkpoint inhibitor treatment in patients with locally advanced or metastatic solid tumors who achieved a partial or complete response after 6 months of standard-dose immunotherapy.

• Key Outcomes: Reduced-frequency immunotherapy failed to demonstrate noninferiority for progression-free survival compared with standard treatment and was associated with a higher risk of death. No meaningful differences in grade 3/4 immune-related adverse events or serious adverse events were observed between treatment groups.

• Clinical Relevance: These findings challenge routine immunotherapy de-escalation in patients with responding advanced or metastatic cancer, highlighting potential risks associated with extending dosing intervals and supporting further investigation of individualized, biomarker-guided treatment strategies.

Results from the phase 3 MOIO trial demonstrated that reducing the frequency of immune checkpoint inhibitor treatment failed to establish progression-free survival (PFS) noninferiority compared with standard dosing in patients with responding advanced or metastatic solid tumors, with a signal of inferior overall survival (OS) and no meaningful safety advantage.

These findings were presented by Gwenaëlle Gravis, MD, Institut Paoli-Calmettes, Marseille, France, during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress.

In this multicenter, noninferiority trial, 340 patients with locally advanced or metastatic solid tumors who had achieved a partial or complete response after 6 months of standard-dose immunotherapy were randomized to continue standard-frequency treatment or receive reduced-frequency immunotherapy every 3 months at the same dose.Patients with melanoma who had achieved a complete response were excluded from trial enrollment. 

The primary end point was PFS, with noninferiority defined by a hazard ratio (HR) margin of 1.3. Secondary end points included OS, duration of response, and safety.

The trial planned to enroll up to 646 patients and included 2 prespecified interim futility analyses to evaluate whether reduced-frequency treatment should continue to be investigated.

At a median follow-up of 18.6 months, the modified intent-to-treat analysis included 308 patients. Median PFS was 25 months with standard-frequency immunotherapy compared with 21.9 months with reduced-frequency treatment. Reduced-frequency immunotherapy did not demonstrate PFS noninferiority and crossed the prespecified futility boundary (HR, 1.35; 95% confidence interval [CI], 0.9 to 2; P = .0635).

A signal of inferior OS was also observed with reduced-frequency immunotherapy, which was associated with a higher risk of death compared with standard-frequency treatment (HR, 2; 95% CI, 1.1 to 3.9; P = .0143).

Treatment effects varied according to tumor type and line of therapy. Among patients with urothelial cancer, the HR for PFS was 2.9 (95% CI, 1.3 to 6.7), while the HR was 1.6 (95% CI, 0.8 to 3.1) among patients with lung cancer.

In contrast, PFS estimates numerically favored reduced-frequency treatment in patients with renal cell carcinoma (HR, 0.7; 95% CI, 0.3 to 1.5) and head and neck cancer (HR, 0.6; 95% CI, 0.1 to 2.4), although the confidence intervals were wide.

Among patients receiving immunotherapy beyond the first-line setting, the HR for PFS was 2.9 (95% CI, 0.9 to 4.9).

Grade 3/4 immune-related adverse events occurred in 10.5% of patients receiving standard-frequency immunotherapy compared with 9.5% receiving reduced-frequency treatment. Serious adverse events were reported in 26.3% and 25% of patients, respectively.

The similar rates of severe immune-related adverse events and serious adverse events indicate that reducing immunotherapy frequency did not provide a meaningful safety advantage.

The investigators concluded that reduced-frequency immune checkpoint inhibitor treatment failed to establish PFS noninferiority and was associated with a signal of inferior survival, arguing against a uniform immunotherapy de-escalation strategy in patients with responding advanced or metastatic cancer. Further evaluation of biomarker-driven approaches may help identify patients who could safely receive less intensive treatment.

Source: 

Gravis G, Barthelemy P, Korakis I, 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. Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA10.