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Kaimen Rigor review

Sacituzumab tirumotecan versus docetaxel for previously treated <i>EGFR</i>-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial

Fang W, Li X, Wang Q, Meng X, Zheng W, Sun L, Yao W, Zhuang W, Fan Y, Zhuo M, Luo Y, Zhang Z, Song X, Yang R, Yang J, Jin X, Diao Y, Ge J, Zhang L.

DOI: 10.1136/bmj-2025-085680
Record issued: 2026-08-10
Engine: 7.29.0
Exported: 2026-09-20

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/8fe57e33-804a-448e-90aa-8aa21c75f115 is authoritative.

Kaimen Rigor review

Kaimen 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★
ReportingKey resources partially met−0.25★
ReportingStatistical analysis partially met−0.25★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.29.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run on this paper: the pass that reads its reported means did not complete. No reported mean was checked for arithmetic impossibility.

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
Primary endpoint is objective response rate (ORR), a surrogate biomarker. No target engagement data at the tested dose is provided, and no validated evidence linking ORR to clinical outcome (e.g., overall survival) in this specific patient population is cited.
“The primary endpoint was objective response rate as assessed by a blinded independent review committee.”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 202OverreachOverstated conclusions 03AuthenticityNone found 304DisclosureReporting gaps 05AvailabilityNone found 106CopyeditCopyediting

This Kaimen Rigor review uses Kaimen 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-designed and transparently reported phase 2 randomised controlled trial with strong methods, ethics documentation, and registration. The main weaknesses are reporting-level: several key p-values are printed only as thresholds, the analysis code is not in a version-controlled repository with a DOI, a CONSORT checklist is not referenced, and the docetaxel comparator's manufacturer is not stated.

Both reviewers converged on 7 of 8 dimensions; the key resources divergence (warn vs pass) was resolved to pass because both investigational products are fully dosed, with the docetaxel manufacturer omission preserved as a caveat. Statistics verification covered only the 7 recomputable tests (6 consistent, 0 errors); threshold-only p-values and RPSFT could not be machine-verified. No retracted or unresolvable references, no unsupported claims, and no dead data/code links were found.

Numerical inconsistencies

1 finding · worst low

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.

Internal contradictions in the reported numbersAssessed

Recomputed 6 tests: 6 consistent, 0 inconsistent; 6 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Two-sided p for the BIRC objective response rate comparison (sac-TMT 41/91 vs docetaxel 7/45)
“The BIRC assessed objective response rate was 45% (41/91; 95% CI 35% to 56%) in the sac-TMT group and 16% (7/45; 95% CI 7% to 30%) in the docetaxel group, with a difference of 29% (95% CI 15% to 43%; one sided P<0.001)”
Find in source
Taken as given: 41 and 7 are the responder counts of the sac-TMT and docetaxel arms, and 91 and 45 are the group totals, so non-responders are 50 and 38; the 2×2 table is valid with df=1; the paper's actual test was a Cochran-Mantel-Haenszel test stratified by brain metastases, so the plain chi-square is an approximation to check consistency, not an exact reproduction
Method: Pearson chi-square on the 2×2 responder table; two-sided p computed and compared against the reported one-sided P<0.001
How we recomputed it: pChi2x2(41,50,7,38)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Two-sided p for the BIRC progression-free survival hazard ratio derived from its 95% CI
“The sac-TMT group showed a significant 70% reduction in risk of disease progression or death (hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001)”
Find in source
Taken as given: the hazard ratio 0.30 and its 95% CI 0.20 to 0.46 are the point estimate and Wald/normal CI of the log-hazard ratio; the CI is two-sided at the 95% level
Method: SE estimated from CI width, z = log(HR)/SE, two-sided p from the normal CDF; compared against reported one-sided P<0.001
How we recomputed it: pCI(0.30, 0.20, 0.46, 1)
CONSISTENTreported p > .007 · recomputed p = .009Reviewer 1
One-sided p for the overall survival hazard ratio derived from its 95% CI
“The sac-TMT group showed a 51% reduction in risk of death (hazard ratio 0.49, 0.27 to 0.88; one sided P=0.007)”
Find in source
Taken as given: the hazard ratio 0.49 and its 95% CI 0.27 to 0.88 are the point estimate and Wald/normal CI of the log-hazard ratio; the CI is two-sided at the 95% level; the one-sided p for a benefit (HR<1) is the lower-tail normal probability
Method: SE estimated from CI width, z = log(HR)/SE, one-sided p = normalCdf(z); the CI-derived p (~0.009) is slightly larger than the reported log-rank P=0.007 because the CI comes from the Cox model and the p from the log-rank test, so they need not match exactly
How we recomputed it: normalCdf(Math.log(0.49)/((Math.log(0.88)-Math.log(0.27))/(2*1.96)))
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Primary endpoint ORR comparison (sac-TMT 41/91 vs docetaxel 7/45), reported one-sided P<0.001.
“BIRC assessed objective response rate was significantly higher in the sac-TMT group (45% (41/91)) v docetaxel (16% (7/45)), with a difference of 29% (95% confidence interval (CI) 15% to 43%; one sided P<0.001).”
Find in source
Taken as given: 41 is the number of confirmed responses in the sac-TMT arm and 91 its total, so 50 non-responders; 7 is the number of responses in the docetaxel arm and 45 its total, so 38 non-responders; the paper used a one-sided CMH test stratified by brain metastases, so the unstratified Fisher exact p is an approximation
Method: Two-tailed Fisher's exact test on the 2x2 event table; the recomputed p is far below 0.001, consistent with the reported one-sided P<0.001.
How we recomputed it: pFisher2x2(41,50,7,38)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
BIRC-assessed PFS hazard ratio 0.30 (95% CI 0.20-0.46), reported one-sided P<0.001.
“The sac-TMT group showed a significant 70% reduction in risk of disease progression or death (hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001)”
Find in source
Taken as given: the CI (0.20 to 0.46) is a two-sided 95% interval for the hazard ratio; the HR is a ratio, so the log scale is used; the recomputed two-sided p is well below 0.001, consistent with the reported one-sided P<0.001
Method: Two-sided p derived from the reported HR and its 95% CI on the log scale.
How we recomputed it: pCI(0.30,0.20,0.46,1)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
Investigator-assessed PFS hazard ratio 0.23 (95% CI 0.15-0.36), reported one-sided P<0.001.
“investigator assessed median progression-free survival was longer in the sac-TMT group (7.9 months, 95% CI 6.2 to 9.5) compared with 2.8 months (1.5 to 3.8) in the docetaxel group, corresponding to a 77% reduction in the risk of disease progression or death (hazard ratio 0.23, 95% CI 0.15 to 0.36; one sided P<0.001)”
Find in source
Taken as given: the CI (0.15 to 0.36) is a two-sided 95% interval for the hazard ratio; the HR is a ratio, so the log scale is used; the recomputed two-sided p is well below 0.001, consistent with the reported one-sided P<0.001
Method: Two-sided p derived from the reported HR and its 95% CI on the log scale.
How we recomputed it: pCI(0.23,0.15,0.36,1)
UNCOMPUTABLEreported p = .007 · recomputed p = .018Reviewer 2
Overall survival hazard ratio 0.49 (95% CI 0.27-0.88), reported one-sided P=0.007.
“The sac-TMT group showed a 51% reduction in risk of death (hazard ratio 0.49, 0.27 to 0.88; one sided P=0.007)”
Find in source
Taken as given: the CI (0.27 to 0.88) is a two-sided 95% interval for the hazard ratio; the reported p=0.007 is one-sided, so it should be about half of the recomputed two-sided p; the recomputed two-sided p (~0.018) implies a one-sided p (~0.009), consistent with 0.007 given CI rounding
Method: Two-sided p derived from the reported HR and its 95% CI on the log scale; the reported one-sided p is consistent within rounding of the CI.
How we recomputed it: pCI(0.49,0.27,0.88,1)

lowinternal contradiction
The docetaxel arm was randomised with n=46, but the BIRC-assessed full analysis set denominator is 45 (7/45 responders); the trial profile notes four patients had BIRC-verified progression, consistent with one patient lacking measurable disease at baseline, so this is expected rather than a true contradiction.
137 patients were randomised to receive sac-TMT (n=91) or docetaxel (n=46) ... 16% (7/45)
Table 2reviewer’s wording
lowinternal contradiction
Baseline EGFR mutation type is notably imbalanced between arms (Exon 19 deletion 47% sac-TMT vs 70% docetaxel), acknowledged by the authors; this imbalance is a potential confounder for the observed efficacy differences.
“Exon 19 deletion | 43 (47) | 32 (70) | 75 (55)”
Table 1Find in source

Overstated conclusions

2 findings · worst high

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
Conclusions only partially backed by the presented evidenceAssessed

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

partialReviewer 2
Sac-TMT provides benefit over docetaxel across all analysed subgroups.
The claim is plausible but the presented in-text evidence is descriptive; interaction testing is not shown, so 'benefit across all subgroups' is only partially substantiated in the main text.
Evidence: Subgroup analyses referenced in supplementary figures S3A/B and S4A/B; no interaction tests or subgroup-specific CIs are reported in the main text.
Subgroup analyses of objective response rate and progression-free survival, assessed by both BIRC and investigator, showed that sac-TMT provided benefit over docetaxel across all subgroups.
Resultsreviewer’s wording
supportedReviewers 1, 2
Sac-TMT showed statistically significant and clinically meaningful improvements in objective response rate, progression-free survival, and overall survival compared with docetaxel.
The presented results (ORR 45% vs 16%, P<0.001; PFS HR 0.30, P<0.001; OS HR 0.49, P=0.007 at interim) directly support the claim, with the OS result appropriately tied to a prespecified interim analysis.
Evidence: BIRC ORR 45% vs 16% (difference 29%, 95% CI 15%-43%, P<0.001); PFS HR 0.30 (95% CI 0.20-0.46); OS HR 0.49 (95% CI 0.27-0.88, one-sided P=0.007).
“Sac-TMT showed statistically significant and clinically meaningful improvements in objective response rate, progression-free survival, and overall survival compared with docetaxel”
ConclusionFind in source
supportedReviewers 1, 2
The 12-month overall survival rate was 73% with sac-TMT and 54% with docetaxel.
These figures are reported directly from the interim OS analysis and are internally consistent with the hazard ratio.
Evidence: Reported in Results/Abstract with 95% CIs (62%-81% and 39%-67%).
“The 12 month overall survival rate was 73% with sac-TMT and 54% with docetaxel (hazard ratio 0.49, 0.27 to 0.88; one sided P=0.007)”
AbstractFind in source
supportedReviewer 1
After adjustment for crossover, sac-TMT showed improved overall survival.
The RPSFT-adjusted analysis is presented with a hazard ratio and CI, directly supporting the claim.
Evidence: RPSFT-adjusted OS HR 0.36 (95% CI 0.20-0.66); censoring-at-crossover HR 0.33 (95% CI 0.18-0.62).
“After adjustment for crossover using the rank-preserving structural failure time model, sac-TMT also showed improved overall survival (hazard ratio 0.36, 0.20 to 0.66)”
AbstractFind in source
supportedReviewer 1
Grade ≥3 treatment-related adverse events were less frequent with sac-TMT than with docetaxel.
The safety data directly support the claim (56% vs 72%), with detailed per-event tables provided.
Evidence: Grade ≥3 TRAEs 51/91 (56%) sac-TMT vs 33/46 (72%) docetaxel; no febrile neutropenia in sac-TMT vs 20% in docetaxel.
“Grade ≥3 treatment related adverse events were less frequent with sac-TMT than with docetaxel (56% v 72%)”
Table 3Find in source
supportedReviewer 1
This study provides evidence supporting sac-TMT as an effective treatment for these patients with disease progression after treatment with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.
The claim is proportionate to a phase 2 trial: the efficacy signals are robust, and the authors appropriately note the surrogate primary endpoint and caution about the interim nature of OS.
Evidence: Consistent ORR/PFS/OS benefits across BIRC and investigator assessments; acknowledged limitations.
“This study provides evidence supporting sac-TMT as an effective treatment for these patients with disease progression after treatment with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.”
ConclusionFind in source
supportedReviewer 2
Sac-TMT reduced the risk of death compared with docetaxel after adjustment for crossover.
The crossover-adjusted survival benefit is supported by two supplementary analyses reported in the results.
Evidence: RPSFT-adjusted HR 0.36 (95% CI 0.20-0.66) and a censoring-adjusted HR 0.33 (0.18-0.62) are reported.
“After adjustment for crossover using the rank-preserving structural failure time model, sac-TMT also showed improved overall survival (hazard ratio 0.36, 0.20 to 0.66).”
AbstractFind in source
supportedReviewer 2
The China National Medical Products Administration has approved sac-TMT as the first TROP2-directed ADC for lung cancer worldwide.
The claim is a reported regulatory fact rather than a data-derived inference from this paper, and is presented as such.
Evidence: This is stated as a regulatory fact in the conclusions; the trial itself provides the efficacy data but not the approval documentation.
“the China National Medical Products Administration has recently approved the use of sac-TMT, establishing it as the first trophoblast cell surface antigen 2 directed antibody-drug conjugate approved for the treatment of lung cancer in the world.”
ConclusionFind in source

Premise concern: surrogate not validated for clinical benefit.

INADEQUATESurrogate endpoint
Primary endpoint is objective response rate (ORR), a surrogate biomarker. No target engagement data at the tested dose is provided, and no validated evidence linking ORR to clinical outcome (e.g., overall survival) in this specific patient population is cited.
“The primary endpoint was objective response rate as assessed by a blinded independent review committee.”
Find in source
ADEQUATEEffect size
ORR 45% vs 16% (difference 29%), PFS HR 0.30, OS HR 0.49. These are large effect sizes, and the authors explicitly state they are clinically meaningful.
“Sac-TMT showed statistically significant and clinically meaningful improvements in objective response rate, progression-free survival, and overall survival.”
Find in source

Data authenticity concerns

None found

An adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.

Checked — nothing surfaced.

Reporting gaps

3 findings · worst high

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Statistical reporting gaps (tests, assumptions, effect sizes)Assessed
Data/code availability incompleteAssessed
Key resources under-identified (antibodies, cell lines, RRIDs)Assessed

Eight Dimensions5 pass · 3 warn

The introduction cites the epidemiology of EGFR-mutated NSCLC, the mechanism of the novel ADC (increased internalisation with EGFR mutations), and prior phase 1/2 activity. It explicitly discusses why prior phase 3 trials (EVOKE-01, TROPION-Lung01) failed and how this trial's molecularly targeted population addresses those limitations. The hypothesis follows directly from this evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The paper establishes a clear scientific foundation: prior work on TROP-2-directed ADCs, the unmet need in EGFR-mutated NSCLC, and a mechanistic rationale for sac-TMT in this molecularly defined population.

Evidence

paraphrase[Introduction, paragraphs 2-3]

“Two trophoblast cell surface antigen 2 directed antibody-drug conjugates, sacituzumab govitecan and datopotamab deruxtecan, have both shown promising clinical activity in advanced NSCLC in phase 1 and phase 2 trials. However, randomised phase 3 trials ... did not reach statistical significance for overall survival improvement.”

“Notably, EGFR -mutated NSCLC cell lines resistant to tyrosine kinase inhibitors showed an even higher uptake rate of sac-TMT than cells naive to tyrosine kinase inhibitors.”

Introduction ¶4Find in source

paraphrase[Discussion, 'Comparison with other studies']

“Unlike TROPION-Lung01 and EVOKE-01, which enrolled unselected NSCLC populations, this trial focused specifically on EGFR-mutant patients guided by mechanistic evidence of enhanced sac-TMT uptake.”

PASSReviewer 2· 90% conf

The rationale is well established: the unmet need in EGFR-mutated NSCLC after TKI/platinum failure, the biological rationale for targeting TROP2, and the failures of prior TROP2 ADCs are all cited and used to justify the molecularly enriched design.

Evidence

“Mechanistic exploration in a recent study has shown that the presence of EGFR mutations substantially increases the internalisation and lysosomal uptake of sac-TMT.”

Introduction ¶2Find in source

“The EVOKE-01 trial population was heterogeneous, with a low proportion of patients with actionable genomic alterations that were potentially responsive to the corresponding targeted therapies”

DiscussionFind in source

“It is imperative that higher level evidence from randomised controlled trials be obtained in this molecularly targeted population.”

IntroductionFind in source

For a human RCT, the applicable criteria are randomization_method, randomization_unit, blinding_levels, power_analysis, inclusion_exclusion, and outlier_handling (mapped to analysis-population definition). All are reported adequately: SAS-generated stratified block randomisation with centralised randomisation system; open-label stated with a masked BIRC; 85% power calculation with stated effect size and alpha; detailed eligibility; and ITT/full-analysis/safety populations defined. The remaining bench-oriented criteria are not applicable to this design.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The trial design is rigorous: randomisation method and stratification stated, a priori power calculation given, open-label design with masked BIRC evaluation, and clear analysis populations defined.

Evidence

“An independent statistician generated the 2:1 randomisation schedule using SAS software (version 9.4). A stratified block design was applied, with stratification by brain metastases (yes or no).”

MethodsFind in source

“With a planned enrolment of about 126 patients, the trial had at least 85% power to detect a 25% difference (docetaxel 10%; sac-TMT 35%) in objective response rate at a one sided α of 0.025.”

Statistical analysisFind in source

“The treatment assignment was not masked to investigators and participants, but the central evaluation by a blinded independent review committee (BIRC) was conducted in a masked manner.”

MethodsFind in source

PASSReviewer 2· 90% conf

Randomisation method, patient-level randomisation unit, open-label design with masked BIRC assessment, a priori power calculation, eligibility criteria, and the analysis populations are all clearly described.

Evidence

MethodsFind in source

“The treatment assignment was not masked to investigators and participants, but the central evaluation by a blinded independent review committee (BIRC) was conducted in a masked manner.”

MethodsFind in source

“With a planned enrolment of about 126 patients, the trial had at least 85% power to detect a 25% difference (docetaxel 10%; sac-TMT 35%) in objective response rate at a one sided α of 0.025.”

Statistical analysisFind in source

Sex (44% men, 60/137) and age (median 56 years) are reported in text and Table 1, with ECOG performance status and cancer stage as health measures. Race/ethnicity is effectively single-population (all Chinese, noted in Limitations). Comorbidities are not tabulated, so demographics is only partially adequate; the other applicable items are adequate.

Sub-criteria

demographicsINADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 70% conf

Sex, age, and health status (ECOG, stage) are thoroughly reported in Table 1; demographic breadth is limited because comorbidities and race/ethnicity are only partially described.

Evidence

“44% (60/137) were men”

ResultsFind in source

paraphrase[Results, 'Patients' and Table 1]

“The median age of the study population was 56 years ... ECOG performance status 1 | 76 (84) | 37 (80) | 113 (82)”

“the enrolled patients were all Chinese, which may limit the generalisability of the findings”

LimitationsFind in source

PASSReviewer 2· 65% conf

Sex and age/health status are well reported, but the demographics sub-criterion is only partially met because race/ethnicity and comorbidities are not presented in the baseline table.

Evidence

“44% (60/137) were men”

ResultsFind in source

“The median age of the study population was 56 years”

ResultsFind in source

“the enrolled patients were all Chinese, which may limit the generalisability of the findings”

LimitationsFind in source

All three applicable criteria are adequate: a named ethics body (ethics committee of Sun Yat-sen University Cancer Centre) with a protocol number and date of approval; written informed consent before enrolment; and a named regulatory framework (Declaration of Helsinki, GCP). IACUC is not applicable to a human trial.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

Ethical compliance is fully documented: a named ethics committee with protocol number approved the study, written informed consent was obtained, and compliance with the Declaration of Helsinki and GCP is stated.

Evidence

“The study protocol was reviewed and approved by the ethics committee of Sun Yat-sen University Cancer Centre on 14 October 2022 (A2022-175-01) and at each participating centre before initiation.”

EthicsFind in source

“All patients provided written informed consent before enrolment.”

MethodsFind in source

“This study was conducted in accordance with the principles of the Declaration of Helsinki, good clinical practice guidelines, and applicable laws and regulations.”

EthicsFind in source

PASSReviewer 2· 95% conf

A named ethics committee approved the protocol with a protocol number, written informed consent is documented, and compliance with the Declaration of Helsinki and GCP is stated.

Evidence

EthicsFind in source

“All patients provided written informed consent before enrolment.”

MethodsFind in source

“This study was conducted in accordance with the principles of the Declaration of Helsinki, good clinical practice guidelines, and applicable laws and regulations.”

EthicsFind in source

Sac-TMT and docetaxel are both named with complete dose/regimen; sac-TMT is the sponsor's product, but docetaxel's manufacturer/source and formulation are not given. The TROP-2 IHC assay uses monoclonal antibody EPR20043 (protein link provided) by MEDx Translational Medicine. Statistical software (SAS 9.4) and analysis code (supplementary) are identified. Applicable criteria are 1 of 2 adequate.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 60% conf

The investigational products are named with full dosing regimens and SAS is identified with version, but the docetaxel comparator's manufacturer/source and formulation are not specified, and the IHC antibody is only partially identified.

Evidence

paraphrase[Methods, 'Interventions']

“Sac-TMT was administered intravenously at 5 mg/kg on days 1 and 15 of each four week cycle ... Docetaxel was administered intravenously at a dose of 75 mg/m 2 every three weeks”

“All statistical analyses were conducted using SAS software (version 9.4).”

Statistical analysisFind in source

absence[Methods, 'Interventions']

Docetaxel manufacturer/source and formulation not specified

PASSReviewer 2· 70% conf

The investigational products (sac-TMT and docetaxel) are named with doses and regimens, and the statistical software is identified; the bench-oriented resource criteria are not applicable to this drug trial.

Evidence

“Sac-TMT was administered intravenously at 5 mg/kg on days 1 and 15 of each four week cycle.”

MethodsFind in source

“Docetaxel was administered intravenously at a dose of 75 mg/m 2 every three weeks, on day 1 of each cycle.”

MethodsFind in source

“All statistical analyses were conducted using SAS software (version 9.4).”

Statistical analysisFind in source

Tests are named (CMH, stratified log-rank, Cox, Kaplan-Meier, Clopper-Pearson), assumptions are handled by design (Cox with Efron tie handling, prespecified RPSFT assumption), effect sizes with 95% CIs are reported throughout, SAS 9.4 is identified, and data presentation follows the clinical idiom. Verified arithmetic: all baseline and safety percentages recompute correctly (e.g., 41/91=45%, 51/91=56%, all Table 1 percentages reconcile). The exact_p_values sub-criterion is only partially met because the primary ORR and PFS comparisons are printed as 'one sided P<0.001' rather than exact values (OS is reported exactly as P=0.007). Per the scoring rule, imprecise (threshold) p-value reporting warrants a warn even though no errors are present.

Sub-criteria

tests namedADEQUATE

exact p valuesINADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 60% conf

Statistical methods are fully named with effect sizes and 95% CIs, and all tabulated percentages are arithmetically consistent, but several p-values are printed only as thresholds ('one sided P<0.001') rather than exact values.

Evidence

“Treatment groups were compared using the Cochran-Mantel-Haenszel test, stratified by the presence of brain metastases.”

Statistical analysisFind in source

“with a difference of 29% (95% confidence interval (CI) 15% to 43%; one sided P<0.001)”

AbstractFind in source

“hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001”

ResultsFind in source

WARNReviewer 2· 70% conf

Statistical methods, effect sizes with CIs, software, and data presentation are excellent, and all arithmetic checks pass, but several key p-values are reported only as thresholds ('one sided P<0.001') rather than exact values.

Evidence

“Treatment groups were compared using the Cochran-Mantel-Haenszel test, stratified by the presence of brain metastases.”

Statistical analysisFind in source

“with a difference of 29% (95% CI 15% to 43%; one sided P<0.001)”

ResultsFind in source

“hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001”

ResultsFind in source

The data-availability statement names a concrete public repository (Mendeley URL), which is adequate. However, the code is provided only as supplementary files rather than a version-controlled public repository with a permanent identifier, and no DOI/accession is given for the dataset. Accession numbers are not applicable (no sequencing data). 1-2 of 3 applicable criteria are adequate.

Sub-criteria

code sharingINADEQUATE

accession numbersN/A

repository depositINADEQUATE

data availability statementADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 70% conf

A concrete data-availability statement points to an open Mendeley dataset, but the analysis code is only in supplementary files and the dataset lacks an explicit DOI/accession.

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/hts8z9mx4w/1”

Data availabilityFind in source

“The code used to analyse the data in the paper can be found in the supplementary files.”

Data availabilityFind in source

absence[Data availability statement]

No DOI/accession is stated for the dataset

WARNReviewer 2· 70% conf

The data availability statement is concrete (open Mendeley dataset with URL), but the analysis code is only placed in supplementary files rather than a version-controlled public repository with a persistent identifier.

Evidence

“The data underlying the findings in this paper are openly and publicly available and can be found at https://data.mendeley.com/datasets/hts8z9mx4w/1”

Data availabilityFind in source

“The code used to analyse the data in the paper can be found in the supplementary files.”

Data availabilityFind in source

The trial is registered (NCT05631262), methods are detailed enough for replication, all outcomes (ORR, DCR, PFS, TTR, DOR, OS, safety) are reported including a null biomarker finding, and limitations (sample size, single-country, surrogate primary endpoint, no QoL) are discussed. A CONSORT checklist is not referenced, though a trial-profile figure is present. Funding and ICMJE COI disclosures are complete.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 80% conf

Reporting is complete and transparent: trial registered, methods detailed, all pre-specified endpoints reported, limitations explicitly discussed, and funding/COI statements provided; only an explicit CONSORT checklist reference is absent.

Evidence

“Trial registration ClinicalTrials.gov NCT05631262”

AbstractFind in source

“Although the modest sample size was appropriate for this phase 2 trial, the enrolled patients were all Chinese, which may limit the generalisability of the findings.”

LimitationsFind in source

“This study was funded by Sichuan Kelun-Biotech Biopharmaceutical and partly supported by the National Natural Science Foundation of China”

FundingFind in source

PASSReviewer 2· 80% conf

Methods are detailed, the trial is registered with a number, outcomes are fully reported, limitations and funding/COI are disclosed, and conclusions are proportional to the evidence.

Evidence

“ClinicalTrials.gov NCT05631262”

AbstractFind in source

“Although the modest sample size was appropriate for this phase 2 trial, the enrolled patients were all Chinese, which may limit the generalisability of the findings.”

LimitationsFind in source

“This study was funded by Sichuan Kelun-Biotech Biopharmaceutical and partly supported by the National Natural Science Foundation of China”

FundingFind in source

Registered (4 IDs: ClinicalTrials.gov). No reporting guideline cited.

ClinicalTrials.gov

ClinicalTrials.gov

ClinicalTrials.gov

ClinicalTrials.gov

Broken references and links

None found

References checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.

Checked — nothing surfaced.

Checked 29 references by DOI: 29 verified.

Every extracted reference resolved against Crossref/OpenAlex with no retraction flags.

1 data/code link checked; 1 live.

dataMendeley DataLIVEHTTP 200
https://data.mendeley.com/datasets/hts8z9mx4w/1
Resolves to Mendeley Data (data repository).

Copyediting

1 finding · worst low

Wording, consistency and formatting errors that need correcting before submission.

Wording or formatting errors that need correctingAssessed

4 copyedit issues flagged (1 major): mostly punctuation, consistency, clarity.

MAJORpunctuationAuthor byline (title page)
“Fang Wenfeng professor Li Xingya professor Wang Qiming professor Meng Xiangjiao professor Zheng Wei professor Sun Longhua professor”
→ Separate author names from academic titles with commas or line breaks, e.g., 'Wenfeng Fang, professor; Xingya Li, professor; ...'
The byline runs names and titles together with no separators, making authorship attribution hard to parse.
MINORconsistencyEnd of article (Associated Data block)
“Associated Data Supplementary Materials Supplementary information: Clinical study protocol ... Data Availability Statement The code used to analyse the data in the paper can be found in the supplementary files.”
→ Remove the duplicated data-availability statement and supplementary-materials list that repeat the earlier sections.
The data-availability statement and supplementary list appear twice in the article.
MINORclarityAuthor byline
“Fang Wenfeng professor Li Xingya professor Wang Qiming professor Meng Xiangjiao professor Zheng Wei professor ...”
→ Separate author names from roles and affiliations with commas or line breaks (e.g., 'Fang Wenfeng, professor; Li Xingya, professor; ...').
Author names and academic titles are run together without separators, making the byline hard to parse.
MINORotherHeader/journal metadata
“389 e085680 e085680”
→ Remove the duplicated article identifier 'e085680' and confirm the page/article number is formatted once.
Stray journal metadata string appears before the Abstract; likely a rendering artifact but should be cleaned.

Kaimen Rigor Action ItemsFinal pass before journal submission

The published work is methodologically robust and internally consistent; no validity threats warrant retraction. An informed reader should weigh the reporting gaps — exact p-values for ORR/PFS, code availability in a permanent repository, and the missing CONSORT checklist — as minor transparency issues that would justify a correction or erratum, and should interpret the single-country phase 2 design and the baseline EGFR-mutation imbalance as interpretative caveats.

1.
HIGHstatistics
Report the exact p-values for the primary ORR comparison and the PFS comparison (currently printed only as 'one sided P<0.001') in the Abstract and Results/'Efficacy' sections.
Threshold-only p-values for primary endpoints are imprecise reporting and prevent readers and meta-analysts from assessing the exact strength of evidence.
2.
HIGHcopyedit
Fix the author byline so names and academic titles are separated (e.g., 'Wenfeng Fang, professor; Xingya Li, professor; ...') on the title page.
The run-together names and titles make authorship attribution hard to parse and would be flagged by a copyeditor or reader.
3.
MEDIUMdata code
Deposit the analysis code in a version-controlled public repository with a persistent DOI (e.g., Zenodo or a GitHub release) and update the Data availability statement to point to it.
Code confined to supplementary files lacks a permanent identifier, limiting reproducibility and long-term access.
4.
MEDIUMcopyedit
Remove the duplicated data-availability statement and supplementary-materials list that repeat earlier sections at the end of the article.
Duplicated reporting blocks are confusing and should be consolidated into a single statement.
5.
MEDIUMreporting
Reference the CONSORT reporting checklist in the Methods (or add a completed checklist to the supplementary appendix).
A CONSORT reference is expected for a randomised trial and closes the only reporting-transparency gap identified.
6.
LOWreporting
Add race/ethnicity and relevant comorbidity detail to Table 1 or a supplementary baseline table.
The demographics sub-criterion is only partially met because these baseline characteristics are not tabulated.
7.
LOWrigor
State the manufacturer and formulation/strength of the docetaxel comparator in the Interventions section.
Full identification of the comparator supports replication; the current dosing information is adequate but the source is unspecified.
8.
LOWcopyedit
Clean the stray duplicated article identifier 'e085680' in the header/journal metadata before the Abstract.
The duplicated identifier is a rendering artifact that should be removed for a clean published record.
9.
LOWrigor
In the Discussion, explicitly address the potential confounding effect of the baseline EGFR-mutation imbalance (Exon 19 deletion 47% sac-TMT vs 70% docetaxel) on the efficacy estimates.
The acknowledged imbalance is a potential confounder for the observed efficacy differences and deserves an explicit sensitivity or interpretive statement.

Full text (52,039 chars)Analyzed: Aug 10, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”

How stars are deducted

Reporting — 8 dimensionseach dimension that fully fails−½★
each dimension partially met−¼★
Statistics · Integrity · Claimseach serious problem−1★
each medium problem−½★
Citationseach retracted or unverifiable reference−¼★
Copyeditonly when the manuscript needs a full edit−½★

The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.

The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.

This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.

Sacituzumab tirumotecan versus docetaxel for previously treated <i>EGFR</i>-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial

Fang W, Li X, Wang Q, Meng X, Zheng W, Sun L, Yao W, Zhuang W, Fan Y, Zhuo M, Luo Y, Zhang Z, Song X, Yang R, Yang J, Jin X, Diao Y, Ge J, Zhang L.

DOI

10.1136/bmj-2025-085680

Record issued

2026-08-10

Engine

7.29.0

Exported

2026-09-20