Top KOLs Discussing MOIO
MOIO Key Slides & Visuals
ESMO 2026 slides
| Standard ICI | Reduced ICI (every 12 weeks) | HR (96.16% CI); one-sided P | |
|---|---|---|---|
| mITT population, n | 152 | 156 | — |
| PFS events, n (%) | 54 (35.5) | 66 (42.3) | — |
| Median PFS, months (95% CI) | 25.0 (19.4–NE) | 21.9 (12.1–31.6) | 1.35 (0.90–2.04); P = 0.0635 |
| Randomized and treated population, n | 171 | 168 | — |
| PFS events, n (%) | 60 (35.09) | 70 (41.67) | — |
| Median PFS, months (95% CI) | 25.00 (19.35–NE) | 23.49 (12.12–32.69) | 1.28 (0.86–1.90); P = 0.0976 |
| Patients at risk at 12 / 24 months (mITT) | 82 / 27 | 62 / 24 | — |
Same slides also posted by @Tony_Calles.
| Standard ICI | Reduced ICI (every 12 weeks) | HR (95% CI); P | |
|---|---|---|---|
| mITT: deaths, n (%) | 16 (10.5) | 31 (19.9) | — |
| mITT: median OS | Not reached | Not reached | 2.04 (1.08–3.85); two-sided P = 0.0286 |
| Randomized and treated: deaths, n (%) | 18 (10.53) | 32 (19.05) | — |
| Randomized and treated: median OS | Not reached | Not reached | 1.89 (1.03–3.48); P = 0.0400 |
| Patients at risk at 12 / 24 months (mITT) | 100 / 47 | 95 / 37 | — |
Same slides also posted by @Tony_Calles.
| Standard ICI | Reduced ICI (every 12 weeks) | |
|---|---|---|
| Median age, years (IQR) | 69.0 (60–75) | 71.0 (63–76) |
| Complete / partial response at randomization | 32.9% / 67.1% | 29.5% / 70.5% |
| First-line treatment at randomization | 74.3% | 75.0% |
| PD-1 / PD-L1 inhibitor | 80.9% / 19.1% | 80.1% / 19.9% |
| Lung cancer | 46 (30.3%) | 47 (30.1%) |
| Urothelial carcinoma | 40 (26.3%) | 38 (24.4%) |
| Renal cell carcinoma | 29 (19.1%) | 29 (18.6%) |
| Head and neck cancer | 11 (7.2%) | 10 (6.4%) |
| Other tumor types (10 types, 0–6 patients each per arm) | 26 (17.1%) | 32 (20.5%) |
KOL-Made Infographics
Summary graphics designed by physicians (not conference slides), made from the abstract before the presentation. Values are as the authors drew them. Context: graphics quoting the abstract’s “exceeding the prespecified futility boundary” refer to the one-sided P value (0.0635) being above the 0.0192 stopping threshold; the presented slide states the threshold was not crossed. Click to enlarge.
@ChandrakanthMv
@ChandrakanthMv
@ChandrakanthMv
@ChandrakanthMv
@DrRishabhOnco
@jryckman3De-escalation, margins and a mixed population
Is one non-inferiority margin right for every tumor type?
Naidoo asked whether a non-inferiority HR of 1.3 is acceptable for all ICI-eligible tumors, and who should set it: clinicians, patients or regulators. Her slide noted that non-inferiority margins are poorly defined in oncology trials, with the margin justified in 33.3% and missing in 54.3% of non-inferiority trials in the literature she cited. ESMO reports her view that the threshold used to define non-inferiority needs to be closely examined, with input from clinicians, patients and regulators. Prof. Tom John asked the same question on X: “Who defines non-inferiority?”
LBA10 discussant slides (Jarushka Naidoo, ESMO 2026) · ESMO Insights, Oct 26, 2026A pragmatic, pan-tumor design
MOIO enrolled 14 tumor types, multiple ICI combinations and a range of responses at 6 months. Naidoo concluded that pan-tumor non-inferiority “may not have been the ideal trial, given heterogeneity of ICI responses & pharmacology,” and that ICI de-intensification is unlikely to be “one-size-fits-all.” Tom John called the design “Pragmatic but messy” with “small numbers,” and Stephen V Liu, MD, highlighted “lessons on trial design, non-inferiority, and pragmatism.”
LBA10 discussant slides (Jarushka Naidoo, ESMO 2026)Why every 3 months, and what comes next
Naidoo asked whether the authors were unlucky with the 3-monthly interval and what its biologic justification was, pointing to receptor occupancy data and the lack of a clear dose-response relationship for nivolumab across melanoma, NSCLC and renal cell carcinoma. Her view of the field: “The field is open: exploring dose, duration, interval & omission, based on biology, pharmacology & clinical principles.” She pointed to designs that have informed the field, such as beat-the-threshold and biomarker-informed trials, and suggested multi-arm multi-stage designs, which may allow several intervals to be tested. Antonio Calles, MD, wrote that personalized dosing can be justified but that “reduced frequency administration of ICI may led to worse clinical outcomes.”
LBA10 discussant slides (Jarushka Naidoo, ESMO 2026) · ESMO Insights, Oct 26, 2026Physician reactions to MOIO
#ESMO26 🚀 Presidential session #3 📌 MOIO is an academic, multicentre, phase III non-inferiority trial conducted across 36 French centres. 🗣️ Dr. Gravis 👫🏽 Pts with locally advanced/metastatic solid tumors in partial or complete response (CR) after 6 months of standard-dose IO were eligible (melanoma in CR excluded) 👉🏽 14 different tumor types 👉🏽 Multiple #ICI combinations 👉🏽👉🏽 Inconclusive study! ❓ Worse OS for NSLC and urothelial ❓ Better OS in HNSCC and RCC ⚠️Are we ok for a HR of 1.3 for non-inferiority threshold? Great discussion by @DrJNaidoo @OncoAlert @myESMO @ASCO @_SEOM @VHIO @brunolarvol 👇🏽👇🏽
MOIO at #ESMO26: 12-week vs standard ICI in patients responding at 6 months. Stopped early, futility bar not crossed. 📉 mITT PFS HR 1.35, median 21.9 vs 25.0 months ⚠️ OS HR 2.04 (1.08 to 3.85), 31 vs 16 deaths (stopped by DSMC) 🧪 UC PFS HR 2.91 (1.27 to 6.67), RCC 0.68 (0.32 to 1.44). Hypothesis-generating. No safety advantage. Results can't support 12-week dosing in responders. Congrats on this huge effort, inferiority trials hard to run, pragmatic trial to better understand schedule of IO therapy. #ESMO26 #GUonc #Immunotherapy
Beautiful discussion of #MOIO at #ESMO26 - a masterclass in distilling a high impact clinical trial into clinically relevant take home messages! Bravo @DrJNaidoo! @OncoAlert https://t.co/pXjqCvBe0J
🚨 3rd Presidential Session at #ESMO26! 💉 Can we safely reduce the frequency of immunotherapy in advanced solid cancers? The phase III MOIO trial tested 12-weekly versus standard immune checkpoint inhibitor administration in responding patients. ⚠️ Unexpected and concerning results! 📉 PFS: HR 1.35 (96.16% CI 0.90–2.04) 🚨 OS: HR 2.04 (95% CI 1.08–3.85), favouring standard treatment! The trial stopped enrolment early following an unexpected OS imbalance. A superb and thought-provoking discussion by @DrJNaidoo Her key messages: -Statistically inconclusive , but clinically reassuring? Certainly not! -Non-inferiority margins matter! Would we really be comfortable accepting a potential 30% increase in the hazard of progression simply to reduce treatment frequency? -One size does not fit all! Different tumour types, different immunotherapy regimens, different biology. Can a pan-tumour de-escalation strategy really work? -Pragmatic does not mean compromising scientific rigour. The take-home message: De-escalation remains an important goal, but it must be biologically justified, clinically meaningful and supported by robust evidence. Doing less is only progress if we can demonstrate that patients are not paying the price in efficacy or survival. 👏 Congratulations to @DrJNaidoo for an outstanding discussion! #ESMO26 #ESMOAmbassadors #Immunotherapy #MOIO #DeEscalation #Oncology
What an elegant discuss. for a negative trial. Managed to contextualize, compare trial designs, and, even when considering worsening HRs when using IO only for 3 months, @DrJNaidoo managed to be quite hopeful on how future IO trials, for de-escalation, are to be designed. #ESMO26 https://t.co/VW8da7Dwoy
@DrJNaidoo : Excellent job summarising the MOIO data and asking key questions. Heterogenous population and choice of endpoints perhaps not ideal. Who defines non-inferiority? Can we use biomarkers? Are there better designs? A brilliant, thought provoking discussion, #LCSM #ESMO26 https://t.co/h6Yp1kbjh4
Excellent discussion by @DrJNaidoo at presidential #ESMO26 on non-inferiority trials and treatment de-escalation in oncology. Less treatment w|out compromising efficacy? The challenges: defining acceptable margins, selecting right patients, ensuring clinically meaningful outcomes https://t.co/IcRG7zwk79
#ESMO26 Dr. Jarushka Naidoo @DrJNaidoo with a fantastic discussion on de-escalation trials in oncology. A call out on why de-escalation studies are important and their limitations. And for MOIO in particular - lessons on trial design, non-inferiority, and pragmatism. A must-listen to all involved in trial design. #ESMOAmbassadors
Gravis: MOIO study looking to show that reduced frequency IO is non-inferior to SoC. Non-inferiority not met. Study stopped early because reduced IO did not reduce toxicity or appear to improve survival. Pragmatic but messy design and small numbers. #LCSM #ESMO26 https://t.co/0qh2ZCBLvK
‼️ While understanding of PK/PD for immune-checkpoint is not fully explained, and personalization in an individualized basis can be justified, reduced frequency administration of ICI may led to worse clinical outcomes. ⚠️ Prospective MOIO non-inferiority trial suggests and stopped earlier due to futility, potential harm ❌ 🫥 When data does not meet wishes. #ESMO26 #LCSM
Context: the presented slide states that the prespecified futility threshold (one-sided P below 0.0192) was not crossed (one-sided P = 0.0635). ESMO reports that the trial was discontinued at the first interim analysis on the recommendation of the independent data monitoring committee, when early overall survival signals appeared to favor standard dosing.
MOIO reduced Hz IO; n340; after 6/12 randomised to standard vs 12w IO; non inferiority design; IDMC stopped and recommended reversion to standard arm; mOS HR 2.04; inferiority esp lung urothelial, not renal;#ESMO26 https://t.co/uhbMkXi6hE
🚨 3rd Presidential Session at #ESMO26! Can we safely reduce the frequency of immunotherapy in advanced solid cancers? The phase III MOIO trial tested 12-weekly versus standard immune checkpoint inhibitor administration in responding patients. ⚠️ Unexpected and concerning OS results! 📉 PFS: HR 1.35 (96.16% CI 0.90–2.04) 🚨 OS: HR 2.04 (95% CI 1.08–3.85), favouring standard treatment! The trial stopped enrolment early following an unexpected OS imbalance. Key message: De-escalation is attractive, but less treatment is not necessarily better! I want to congratulate the authors anyway to run such important study . More follow-up is essential. #ESMO26 #ESMOAmbassadors #Immunotherapy #MOIO #CancerResearch
🚨 #ESMO26 | MOIO (LBA10) Less immunotherapy ≠ same outcomes! Can responding cancer patients receive IO every 3 months? ❌ Phase III MOIO raises a red flag. 📉 PFS: 25 vs 21.9 months (HR 1.35) ⚠️ Death HR: 2.0 ❌ No meaningful safety benefit De-escalation needs evidence, not assumptions. @myesmo @ESMO_open #Immunotherapy @OncoAlert
Posted on October 26 before the presentation, from the abstract released that morning.
MOIO | ESMO 2026 | LBA10 Can we give immunotherapy less often in responders? A phase III non-inferiority trial tested 3-monthly IO versus standard intervals after ≥6 months of response. 🔹 PFS: 21.9 vs 25.0 months | HR 1.35 — non-inferiority NOT established. 🔹 OS: HR 2.00 — concerning survival signal. 🔹 Tumour heterogeneity: Greatest PFS concern in urothelial cancer (HR 2.9); exploratory RCC and H&N estimates remain inconclusive. 🔹 Grade 3–4 immune AEs: 9.5% vs 10.5% — no meaningful safety gain. Take-home: Responding ≠ safe to de-escalate. Routine 3-monthly IO is not supported by these interim findings. Tumour-specific de-escalation requires stronger evidence. Ref: Gravis G et al. MOIO, ESMO 2026, LBA10. @myESMO @OncoAlert #ESMO26 #Immunotherapy #MVOnco
Posted on October 26 before the presentation, from the abstract released that morning.
MOIO (LBA10): IO every 3 months did not achieve PFS noninferiority. 📌 Randomized phase 3 noninferiority trial, 340 pts w/ advanced/metastatic cancer in PR/CR after 6 mo of standard IO; melanoma CR excluded. 📌 Continue standard IO vs the same dose every 3 mo. Interim mITT n=308; median follow-up 18.6 mo. 📌 mPFS 25 vs 21.9 mo; HR 1.35 (95% CI 0.9-2.0), reduced vs standard IO. Prespecified futility boundary exceeded. 📌 Death HR 2.0 (95% CI 1.1-3.9), reduced vs standard IO. 📌 G3-4 irAEs 10.5% vs 9.5%; serious AEs 26.3% vs 25.0% (standard vs reduced IO). https://t.co/cLGRcK0dg9 #ESMO26
Posted on October 26 before the presentation, from the abstract released that morning. Context: abstract LBA10 reports one-sided P = 0.0635 “exceeding the prespecified futility boundary”; the stopping rule was one-sided P below 0.0192, and the presented slide states the futility threshold was not crossed.
ESMO 2026 | A cautionary tale for immunotherapy de-escalation! MOIO Trial (LBA10) – Phase III non-inferiority trial testing 3-monthly immunotherapy vs standard dosing in responding patients with advanced/metastatic cancer. 📊 Key results (N=308): • Median PFS: 21.9 vs 25 months (reduced vs standard; HR 1.35) • Risk of death: HR 2.0 (95% CI 1.1–3.9; p=0.0143) ⚠️ • PFS HR in urothelial cancer: 2.9 • Grade 3–4 immune-related AEs: 9.5% vs 10.5% ❌ Non-inferiority NOT demonstrated. ❌ No meaningful safety advantage. ⚠️ Signal of inferior survival with reduced-frequency IO. 💡 Take-home: Less frequent immunotherapy is not necessarily equally effective! Important: These are interim results with relatively small numbers and heterogeneous tumour types. #ESMO26 #MOIO #Immunotherapy #Oncology @OncoAlert @myESMO
Posted on October 26 before the presentation, from the abstract released that morning.
Can Less Immunotherapy Be Enough? MOIO Tests Treatment De-escalation Can we give less immunotherapy without losing benefit? MOIO tests the same ICI every 3 months vs standard frequency after 6 months of response. Phase III, n=646; PFS non-inferiority is key. Presented by Gwenaëlle Gravis. @myESMO @GroupeUnicancer #ESMO26
Posted on October 21, before the presentation.
MOIO Trial Design
MOIO asked whether patients whose advanced cancer responds to immune checkpoint inhibitors can keep the benefit with less frequent dosing. It is an academic trial sponsored by UNICANCER, the French network of comprehensive cancer centers, and funded by the French National Cancer Institute (INCa, PHRC-K20-150) and La Ligue contre le cancer. Results of the first interim analysis were presented by Gwenaëlle Gravis, MD, at ESMO 2026 (LBA10, Presidential Symposium III, October 26, 2026), with Jarushka Naidoo, MD, as discussant.
Study Design
Randomized 1:1, phase 3 non-inferiority trial (NCT05078047; EUCT 2024-513707-14-00) at 36 French centers. Planned 646 patients; 340 randomized between March 2022 and November 2025. Stratified by response (CR vs PR), PD-1 vs PD-L1 inhibitor, tumor type and line of treatment.
Population
Adults with locally advanced or metastatic solid tumors in complete or partial response after 6 months of standard ICI (RECIST v1.1 or PERCIST v1.0, by investigators), ECOG 0–1; melanoma in complete response excluded. mITT population: lung 30%, urothelial 25%, renal cell 19%, head and neck 7%, 10 other tumor types.
Interventions
Standard arm: continue the same ICI at the same dose and schedule. Reduced arm: the same ICI at the same dose every 12 weeks, until progression, unacceptable toxicity or other stopping criteria. ICIs could be given alone or with another ICI, chemotherapy, bevacizumab or a TKI.
Endpoints
Primary: PFS (non-inferiority margin HR 1.30, upper bound of the 90% CI, final analysis, both co-primary populations). Secondary: OS, response duration and safety; CT.gov also lists cost-effectiveness, iPFS, ORR and quality of life.
Interim Analysis
Futility analyses planned at about 25% and 50% of 498 PFS events; stopping if one-sided P below 0.0192. First interim: 120 events, futility threshold not crossed; trial discontinued on the data monitoring committee’s recommendation (ESMO).
Data Cut
Data cut-off December 1, 2025; median follow-up 18.6 months (standard) and 18.7 months (reduced). mITT 308 patients (152 vs 156); randomized and treated 339 (171 vs 168).
MOIO in the News
MOIO Questions
What is the MOIO trial?
MOIO (NCT05078047; UC-IMM-2101) is an academic, randomized phase 3 non-inferiority trial sponsored by UNICANCER and run at 36 French centers. Adults with an advanced or metastatic solid tumor in complete or partial response after 6 months of standard immune checkpoint inhibitor (ICI) treatment were randomized 1:1 to continue the same ICI on its standard schedule or to receive the same dose every 12 weeks (every 3 months). Melanoma in complete response was excluded. Funding came from the French National Cancer Institute (INCa) and La Ligue contre le cancer.
What did MOIO show at ESMO 2026?
At the first interim analysis (data cut-off December 1, 2025; median follow-up 18.6–18.7 months; 120 PFS events), median PFS in the mITT population was 25.0 months with standard dosing vs 21.9 months with 12-weekly dosing, HR 1.35 (96.16% CI 0.90–2.04), one-sided P = 0.0635. There were 16 vs 31 deaths (10.5% vs 19.9%): OS HR 2.04 (95% CI 1.08–3.85), two-sided P = 0.0286. Results were presented by Gwenaëlle Gravis, MD (LBA10, Presidential Symposium III, October 26, 2026).
Was reduced-frequency immunotherapy non-inferior?
Non-inferiority was not demonstrated. The plan required the upper bound of the 90% CI for the PFS HR to be 1.30 or lower at the final analysis, in both co-primary populations; the trial stopped before a final analysis, and at the interim the 96.16% CI upper bound was 2.04 (the interim analysis tested futility; the non-inferiority test was reserved for the final analysis). The abstract concludes that reduced dose intensity “did not achieve PFS non-inferiority.”
Was reduced-frequency dosing inferior?
Both readings come from the same interim data. The prespecified futility threshold for PFS (one-sided P below 0.0192) was not crossed (P = 0.0635), so inferiority on the primary endpoint was not formally shown. ESMO reports that the independent data monitoring committee recommended stopping the trial at this first interim analysis, after 120 of 498 planned PFS events, when early OS signals appeared to favor standard dosing in key subgroups. OS is a secondary endpoint with medians not reached. The discussant, Jarushka Naidoo, said the study “should be considered neither inferior nor non-inferior,” while the authors’ abstract describes “a signal of inferior survival.”
Did results differ by tumor type?
The abstract reports that the treatment effect differed by the stratification factors tumor type and treatment line. PFS HRs (95% CI) for reduced vs standard dosing were 2.9 (1.3–6.7) in urothelial cancer, 1.6 (0.8–3.1) in lung cancer, 0.7 (0.3–1.5) in renal cell carcinoma and 0.6 (0.1–2.4) in head and neck cancer, and 2.9 beyond first line (the abstract prints the 95% CI as 0.9–4.9). These are exploratory subgroup estimates from small groups (for example, 21 patients with head and neck cancer), and the trial was not powered for them.
Did 12-weekly dosing reduce side effects?
No meaningful difference was seen. Grade 3–4 immune-related adverse events occurred in 10.5% with standard dosing vs 9.5% with 12-weekly dosing, and serious adverse events in 26.3% vs 25.0% (abstract). ESMO reports adverse events leading to treatment discontinuation in 7.0% vs 4.8%.
Does MOIO change how checkpoint inhibitors are dosed?
No drug approval is at stake. The checkpoint inhibitors in MOIO are approved at their labeled schedules, and a 12-week interval is not one of them. Some US labels include a longer-interval option at a higher dose: pembrolizumab (KEYTRUDA) 400 mg every 6 weeks (alongside 200 mg every 3 weeks) and nivolumab (OPDIVO) 480 mg every 4 weeks (alongside 240 mg every 2 weeks). MOIO tested a different approach: the same dose given less often. Other approaches to de-intensification are still being tested, including REFINE-Lung (NCT05085028), which compares pembrolizumab every 9 to 18 weeks with every 6 weeks in NSCLC.