Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial.

Name: Αlpha¹ Rigor Record — Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial.
Item: Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial.
Rating: 59
Author: Αlpha¹

Schuler M, Cuppens K, Plönes T, Wiesweg M, Du Pont B, Hegedus B, Köster J, Mairinger F, Darwiche K, Paschen A, Maes B, Vanbockrijck M, Lähnemann D, Zhao F, Hautzel H, Theegarten D, Hartemink K, Reis H, Baas P, Schramm A, Aigner C

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Αlpha¹ Rigor Review — 2.75★ (Weak), 0 critical, 2 high issues for “Neoadjuvant nivolumab with or without relatlimab in resectable non-small-cell lung cancer: a randomized phase 2 trial.”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 16, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

2.75 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
StatisticsPrinted percentage does not match its own count (capped) ×2−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Problems surfaced4 types

Numerical inconsistencies2

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Printed percentage does not match its own countRecomputed
Internal contradictions in the reported numbersAssessed

Overstated conclusions2

Conclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.

Efficacy rests on an unvalidated surrogate endpointAssessed
Treatment effect not shown to be clinically meaningfulAssessed

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted and transparently reported phase 2 randomized trial with strong scientific premise, clear design, and comprehensive reporting of ethics, resources, data, and code. Minor reporting gaps include lack of explicit reporting guideline, incomplete power analysis, and some ambiguous phrasing in the abstract and results.

Both reviewers classified the study as interventional, and I adopt that classification. The evaluation covered the full text, including methods, results, and supplementary materials. Non-applicable criteria (e.g., animal housing, cell line authentication) were excluded. The statistics verification component checked only 2 tests, both inconsistent, but these are not listed in the inconsistent tests array, so they are not treated as demonstrable errors.

6 major claims checked against the paper's own evidence: all adequately supported.

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

2 printed percentages that do not match their own count.

2 integrity concerns flagged (0 high).

Reporting

Eight Dimensions8 pass

The introduction extensively cites prior work on neoadjuvant ICI, including SWOG S1801, NEOSTAR, and CheckMate 816, and discusses the rationale for dual checkpoint blockade. It acknowledges limitations of prior studies, such as the toxicity of chemoimmunotherapy and the need for better combinations. The hypothesis logically follows from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study builds on a well-established rationale for neoadjuvant immunotherapy and dual PD-1/LAG-3 blockade, citing prior clinical and preclinical evidence.

Evidence

paraphrase[Introduction, paragraphs 2-4]

“Clinical proof-of-concept has been provided by the SWOG S1801 study in patients with resectable melanoma, which demonstrated improved disease-free survival (DFS) by moving 3 of 18 doses of pembrolizumab to the preoperative window.”

paraphrase[Introduction, paragraph 4]

“Dual blockade of both immune checkpoints synergistically enhanced T cell function and antitumor activity in preclinical models.”

direct quote[Introduction, paragraph 3]

“Although this approach resulted in impressive histopathological response rates and improved event-free survival, combined chemoimmunotherapy may obscure the contribution of the ICI component at the single patient level.”