Rigor Reviewed

Rigor-Reviewed Manuscript

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

Name: Adcurare Rigor Record — Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial
Item: Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial
Rating: 100
Author: Adcurare

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.

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Adcurare Rigor Review — 3.25★ (Adequate), 0 critical, 5 high issues for “Sacituzumab tirumotecan versus docetaxel for previously treated <i>EGFR</i>-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial”

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Adcurare Editorial

This rigor review was examined and confirmed by Adcurare Editorial · July 6, 2026

Adcurare Rigor Review

Rigor Reviewed

3.25 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

StatisticsStatistic did not reproduce ×2−1★
ClaimsOverstated claim−0.5★
CitationsUnresolved reference−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.6.0Source: full text

Problems surfaced3 types

Reported statistics do not recompute
Conclusions overstated beyond the evidence
References not resolvable to a published paper

This Adcurare 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 paper on a phase 2 RCT of sacituzumab tirumotecan vs docetaxel in EGFR-mutated NSCLC demonstrates rigorous methodology across most dimensions: strong scientific premise, sound study design with randomisation and BIRC, adequate reporting of biological variables, ethical approvals, and key resources. Two dimensions—data/code availability and reporting transparency—have fixable gaps: code is in supplementary files rather than a citable repository, the CONSORT checklist is missing, and one conclusion slightly overstates the evidence.

Synthesized findings from three independent reviewer models and a copyedit pass. The statistics verification component recomputed 8 reported tests and found 2 minor p-value discrepancies that do not alter conclusions. One reference was flagged as not found in the registry and should be verified. The claim audit identified one overstated conclusion. Dimensions scored as 'not applicable' in checklists were excluded from the score calculation.

12 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

Recomputed 8 tests: 6 consistent, 2 inconsistent, 8 via agent-written checks.

Reporting

Eight Dimensions8 pass

The introduction cites prior research on TROP2 expression in EGFR-mutated NSCLC and the limited efficacy of docetaxel, establishing the unmet need. It discusses the mechanism of sac-TMT and cites phase 1/2 data showing promising activity. The rationale for focusing on the EGFR-mutated population is supported by mechanistic studies showing increased internalisation. Limitations of prior TROP2-directed ADCs (EVOKE-01, TROPION-Lung01) are discussed, including their failure to show overall survival benefit in unselected populations, which the current study aims to address by targeting a molecularly defined subgroup.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study clearly establishes its scientific premise by citing prior work on EGFR-mutated NSCLC treatment, the limitations of current therapies, and the rationale for investigating sacituzumab tirumotecan.

Evidence

direct quote[Introduction, paragraph 1]

“For those whose disease progresses despite both treatments, the latest guidelines recommend single agent chemotherapy, with docetaxel the most widely used agent. However, the efficacy of docetaxel in this patient population remains suboptimal, and concerns about its toxicities persist. These factors underscore an important unmet clinical need for more effective treatment options.”

direct quote[Introduction, paragraph 3]

“Sacituzumab tirumotecan (sac-TMT, also known as MK-2870/SKB264) is a novel antibody-drug conjugate targeting trophoblast cell surface antigen 2, designed using a proprietary Kthiol (pyrimidine-thiol) linker to conjugate the topoisomerase I inhibitor KL610023, with an average drug to antibody ratio of 7.4.”

direct quote[Discussion, paragraph 3]

“Unlike the TROPION-Lung01 and EVOKE-01 studies, which evaluated trophoblast cell surface antigen 2 directed antibody-drug conjugates in NSCLC populations with or without actionable genomic alterations, the current trial specifically focused on patients with NSCLC and sensitising EGFR mutation with disease progression after EGFR-tyrosine kinase inhibitors and platinum chemotherapy.”

PASSReviewer 2· 95% conf

The scientific premise is well-established with a clear rationale linking high TROP2 expression in EGFR-mutated NSCLC to the potential benefit of a TROP2-directed antibody-drug conjugate, and prior work is cited with its limitations acknowledged.

Evidence

direct quote[Introduction, paragraphs 1-3]

“In EGFR-mutated NSCLC, expression of trophoblast cell surface antigen 2 is notably high and may be associated with resistance to EGFR tyrosine kinase inhibitors.”

direct quote[Introduction, paragraphs 4-5]

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

direct quote[Discussion, 'Comparison with other studies']

“The large phase 3 EVOKE-01 trial... reported an objective response rate of 14% and a progression-free survival of 4.1 months, with no statistically significant difference compared with docetaxel.”

PASSReviewer 3· 95% conf

The paper establishes a strong scientific foundation, citing prior studies on EGFR-mutated NSCLC, TROP2-targeting ADCs, and mechanistic evidence for enhanced sac-TMT uptake in EGFR-mutant cells. Limitations of previous trials (EVOKE-01, TROPION-Lung01) are acknowledged and addressed by the study design.

Evidence

direct quote[Introduction, paragraphs 3–4]

“Two trophoblast cell surface antigen 2 directed antibody-drug conjugates... 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.”

direct quote[Introduction, paragraph 5]

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

paraphrase[Introduction, paragraph 4 and Discussion]

“The paper notes that prior phase 3 trials included unselected populations and lacked prespecified subgroup analysis for EGFR-mutant patients, motivating the current focused trial.”

Randomization was performed using a centralized interactive system with stratified block design (by brain metastases). The open-label design is justified by the use of a blinded independent review committee for the primary endpoint. A power calculation is reported (85% power to detect 25% ORR difference). Inclusion/exclusion criteria are detailed, and outlier handling is addressed through ITT, response-evaluable, and safety populations. Replicate distinction and wet-lab controls are not applicable.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study design is robust, featuring a multicentre, open-label, randomised controlled trial with clear randomisation, blinding for outcome assessment, and a power analysis.

Evidence

direct quote[Methods, Randomisation and masking]

“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).”

direct quote[Methods, Randomisation and masking]

“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.”

direct quote[Methods, Statistical analysis]

“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.”

direct quote[Methods, Trial design and participants]

“Eligible patients were aged 18 to 75 years and had histologically or cytologically confirmed non-squamous NSCLC. Patients had either locally advanced (stage IIIB or IIIC) or metastatic (stage IV) disease that was deemed unsuitable for radical surgery or definitive radiotherapy. All patients had sensitising EGFR mutations and disease progression after treatment with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy (in sequential order or in combination) for advanced or metastatic NSCLC.”

PASSReviewer 2· 90% conf

The study design is rigorous for a phase 2 trial, with a clear randomisation method, stratification, a blinded independent review committee, a pre-specified power analysis, and well-defined inclusion/exclusion criteria.

Evidence

direct quote[Methods, 'Randomisation and masking']

“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.”

direct quote[Methods, 'Statistical analysis']

“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.”

PASSReviewer 3· 98% conf

The trial uses an appropriate randomised design with stratification, a pre-specified power analysis, and blinded end-point assessment. All applicable sub-criteria for a human interventional trial are adequately reported.

Evidence

direct quote[Methods, Randomisation and masking]

“the central evaluation by a blinded independent review committee (BIRC) was conducted in a masked manner.”

direct quote[Methods, Statistical analysis]

“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.”

Sex, age, and health status (ECOG performance status) are reported in Table 1. Demographics such as age, sex, and disease characteristics (stage, brain metastases, EGFR mutation type) are comprehensively reported. Species/strain and housing conditions are not applicable for a human trial. The study population is well-characterised.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study adequately reports key demographic and clinical characteristics of the human participants, including age, sex, and disease status.

Evidence

direct quote[Results, Patients]

“The median age of the study population was 56 years, 44% (60/137) were men, 98% had stage IV disease (134/137), and 20% had brain metastases (28/137).”

direct quote[Results, Patients]

“The median age of the study population was 56 years, 44% (60/137) were men, 98% had stage IV disease (134/137), and 20% had brain metastases (28/137).”

direct quote[Table 1]

“Table 1 Baseline personal and clinical characteristics of intention-to-treat population with EGFR -mutated non-small cell lung cancer, according to treatment. Values are numbers (percentages) unless stated otherwise Characteristics | Sac-TMT (n=91) | Docetaxel (n=46) | Total (n=137) | | Median (range) age (years) | 57 (37-75) | 55 (34-74) | 56 (34-75) | | Age ≥65 years | 19 (21) | 8 (17) | 27 (20) | | Men | 38 (42) | 22 (48) | 60 (44) | | Histological type, adenocarcinoma | 91 (100) | 46 (100) | 137 (100) | | Clinical stage: | | | | | IIIb | 2 (2) | 1 (2) | 3 (2) | | IV | 89 (98) | 45 (98) | 134 (98) | | ECOG performance status 1 | 76 (84) | 37 (80) | 113 (82) | | Brain metastases | 18 (20) | 10 (22) | 28 (20) | | Liver metastases | 18 (20) | 7 (15) | 25 (18) | | EGFR mutation type: | | | | | Exon 19 deletion | 43 (47) | 32 (70) | 75 (55) | | L858R mutation | 48 (53) | 14 (30) | 62 (45) | | T790M mutation status: | | | | | Positive | 19 (21) | 10 (22) | 29 (21) | | Negative | 32 (35) | 13 (28) | 45 (33) | | Unknown | 40 (44) | 23 (50) | 63 (46) | | Previous lines of systemic therapy: | | | | | 1* | 9 (10) | 5 (11) | 14 (10) | | 2 | 52 (57) | 20 (43) | 72 (53) | | >2 | 30 (33) | 21 (46) | 51 (37) | | Previous EGFR-TKI treatment: | 91 (100) | 46 (100) | 137 (100) | | Previous third generation EGFR-TKI treatment | 84 (92) | 44 (96) | 128 (93) | | Third generation EGFR-TKI in first line treatment | 54 (59) | 26 (57) | 80 (58) | | Third generation EGFR-TKI in second line treatment | 30 (33) | 18 (39) | 48 (35) | | No previous third generation EGFR-TKI | 7 (8) | 2 (4) | 9 (7) | | Previous antiangiogenic therapy | 60 (66) | 33 (72) | 93 (68) | | Previous immunotherapy | 15 (16) | 6 (13) | 21 (15) | | * Patients had previously progressed after first line treatment with combination regimen of EGFR-TKI and platinum based chemotherapy. ECOG=Eastern Cooperative Oncology Group; EGFR=epidermal growth factor receptor; sac-TMT=sacituzumab tirumotecan; TKI=tyrosine kinase inhibitor.”

PASSReviewer 2· 95% conf

Key biological variables for a human clinical trial, including age, sex, disease stage, and EGFR mutation type, are well-reported in a baseline characteristics table.

Evidence

direct quote[Results, Table 1]

“Median (range) age (years): 56 (34-75); Men: 60 (44%); ECOG performance status 1: 113 (82%)”

direct quote[Results, Table 1]

“EGFR mutation type: Exon 19 deletion: 75 (55%); L858R mutation: 62 (45%)”

PASSReviewer 3· 95% conf

Key biological variables for a human trial (age, sex, health status) are reported in detail. Demographics are well-characterized in Table 1.

Evidence

direct quote[Results, para 1 and Table 1]

“median age of the study population was 56 years, 44% (60/137) were men”

direct quote[Table 1]

“ECOG performance status 1 | 76 (84) | 37 (80) | 113 (82)”

direct quote[Table 1]

“Brain metastases | 18 (20) | 10 (22) | 28 (20)”

The study protocol was approved by the ethics committee of Sun Yat-sen University Cancer Centre and at each participating centre. All patients provided written informed consent.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

The study reports explicit ethical approval from a named ethics committee and states that all patients provided written informed consent.

Evidence

direct quote[Ethics statements, Ethical approval]

“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.”

direct quote[Methods, Trial design and participants]

“All patients provided written informed consent before enrolment.”

direct quote[Ethics statements, Ethical approval]

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

PASSReviewer 2· 95% conf

Ethical approval from a named ethics committee, informed consent, and regulatory compliance are all explicitly reported.

Evidence

direct quote[Ethics statements]

direct quote[Methods, 'Trial design and participants']

“All patients provided written informed consent before enrolment.”

direct quote[Ethics statements]

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

PASSReviewer 3· 98% conf

Ethical approval from a named committee with protocol number is provided, informed consent is documented, and regulatory compliance with the Declaration of Helsinki and GCP is stated.

Evidence

direct quote[Ethical approval section (near end of paper)]

“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)”

direct quote[Methods, Trial design and participants]

“All patients provided written informed consent before enrolment.”

direct quote[Ethical approval section]

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

Sacituzumab tirumotecan and docetaxel are described with their administration details. SAS software version 9.4 is specified for statistical analysis. The antibody used for TROP2 expression assessment is identified by its clone/RRID.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedADEQUATE

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Key resources, including the investigational drugs, software, and the antibody for biomarker analysis, are adequately identified.

Evidence

direct quote[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, on day 1 of each cycle.”

direct quote[Methods, Assessments and endpoints]

“Trophoblast cell surface antigen 2 expression was assessed by immunohistochemistry (monoclonal antibody: EPR20043), performed by MEDx Translational Medicine.”

direct quote[Methods, Statistical analysis]

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

PASSReviewer 2· 90% conf

The investigational products (sac-TMT and docetaxel) are identified with their dosing regimens, and the statistical software is identified. Other wet-lab resources are not applicable for this clinical trial.

Evidence

direct quote[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/m2 every three weeks, on day 1 of each cycle.”

direct quote[Methods, 'Statistical analysis']

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

direct quote[Methods, 'Assessments and endpoints']

“Trophoblast cell surface antigen 2 expression was assessed by immunohistochemistry (monoclonal antibody: EPR20043), performed by MEDx Translational Medicine.”

PASSReviewer 3· 85% conf

The investigational products (sac-TMT and docetaxel) are adequately identified with dose and schedule. The antibody used for IHC is reported but lacks full identification (vendor, catalog, dilution). Software (SAS 9.4) is named. Overall, 2 of 3 applicable criteria are adequate, meeting the pass threshold.

Evidence

direct quote[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/m² every three weeks”

direct quote[Methods, Assessments and endpoints]

“Trophoblast cell surface antigen 2 expression was assessed by immunohistochemistry (monoclonal antibody: EPR20043), performed by MEDx Translational Medicine.”

direct quote[Methods, Statistical analysis]

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

The paper names the CMH test for ORR, log-rank for survival, Cox proportional hazards with Efron tie handling, and RPSFT for crossover adjustment. Exact one-sided p-values (e.g., <0.001, 0.007) and 95% CIs are reported for all primary and secondary endpoints. Effect sizes (HR, difference in proportions) are presented with CIs. SAS 9.4 is stated. Data presentation includes Kaplan-Meier curves, waterfall plots, and tables with per-group n. Error bars are defined as 95% CIs. No internal arithmetic inconsistencies were found; reported percentages are consistent with stated numerators and denominators.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityPASS

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The statistical analysis is well-described, naming specific tests, software, and handling of multiple comparisons. Exact p-values and confidence intervals are reported.

Evidence

direct quote[Methods, Statistical analysis]

“Treatment groups were compared using the Cochran-Mantel-Haenszel test, stratified by the presence of brain metastases. Duration of response, progression-free survival, and overall survival were summarised and presented graphically using the Kaplan-Meier method, with median event times and two sided 95% CIs estimated using the Brookmeyer and Crowley method. Treatment differences in progression-free survival and overall survival were assessed using a stratified log-rank test. Hazard ratios and associated 95% CIs were estimated using a stratified Cox proportional hazards model with Efron’s method for tie handling.”

direct quote[Abstract, Results]

“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).”

direct quote[Methods, Statistical analysis]

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

direct quote[Methods, Statistical analysis]

“The overall type I error rate was strictly controlled at a one sided α of 0.025 by a fixed sequence, closed testing procedure (in the order of BIRC assessed objective response rate, investigator assessed objective response rate, BIRC assessed progression-free survival, investigator assessed progression-free survival, and overall survival), as detailed in the supplementary appendix.”

PASSReviewer 2· 90% conf

Statistical tests are named, a pre-specified analysis plan with multiplicity control is described, exact p-values and confidence intervals are reported, and the software is identified. Data presentation includes Kaplan-Meier curves and waterfall plots.

Evidence

direct quote[Methods, 'Statistical analysis']

“Treatment groups were compared using the Cochran-Mantel-Haenszel test... Treatment differences in progression-free survival and overall survival were assessed using a stratified log-rank test.”

direct quote[Results, 'Efficacy']

direct quote[Methods, 'Statistical analysis']

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

PASSReviewer 3· 95% conf

All statistical sub-criteria are adequately reported. Statistical tests are named, exact p-values and confidence intervals are provided, software is identified, and data presentation includes individual-level plots (waterfall) with per-group n and defined error bars (95% CI). No arithmetic implausibilities are detected.

Evidence

direct quote[Methods, Statistical analysis]

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

direct quote[Results, Efficacy]

direct quote[Methods, Statistical analysis]

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

The data are stated to be openly and publicly available on Mendeley Data with a specific URL. Code for statistical analyses is provided in the supplementary files.

Sub-criteria

code sharingADEQUATE

accession numbersN/A

repository depositADEQUATE

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 100% conf

The paper includes a data availability statement pointing to a public repository for data and supplementary files for code.

Evidence

direct quote[Data availability statement]

“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 .”

direct quote[Data availability statement]

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

PASSReviewer 2· 95% conf

A data availability statement is present with a link to a public repository, and the analysis code is provided in supplementary files.

Evidence

direct quote[Data availability statement]

“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.”

direct quote[Data availability statement]

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

WARNReviewer 3· 90% conf

A data availability statement is present and directs to a public repository (Mendeley). However, code sharing is through supplementary files rather than a version-controlled public repository, which is inadequate by current standards. This results in a 'warn' because not all applicable criteria are adequate.

Evidence

direct quote[Data availability statement]

“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”

direct quote[Data availability statement]

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

The trial is registered on ClinicalTrials.gov. Limitations, including generalisability and power for overall survival, are discussed. Funding sources and conflicts of interest are declared.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The study reports a clinical trial registration number, discusses limitations, and provides funding and conflict of interest statements.

Evidence

direct quote[Abstract, Trial registration]

“ClinicalTrials.gov NCT05631262 (https://clinicaltrials.gov/ct2/show/NCT05631262) .”

direct quote[Limitations of this study]

“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. This trial used the surrogate endpoint of objective response rate as the primary endpoint. The substantial treatment effect on objective response rate could be indicative of survival benefits. Although this study was not adequately powered for overall survival, the key secondary endpoints, including progression-free survival and overall survival, both showed statistically significant improvements through hierarchical fixed sequence testing.”

direct quote[Funding]

“Funding: This study was funded by Sichuan Kelun-Biotech Biopharmaceutical and partly supported by the National Natural Science Foundation of China (grants 82241232 and 82272789 awarded to LZ, grants 82173101 and 82373262 awarded to WF) and Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0519700 awarded to LZ).”

paraphrase[Methods, Assessments and endpoints]

“The primary and secondary endpoints, including objective response rate, disease control rate, progression-free survival, time to response, duration of response, overall survival, and safety, are all reported in the Results section.”

PASSReviewer 2· 90% conf

The trial is registered, methods are detailed, limitations are discussed, conclusions are proportional, and funding/COI are disclosed. A reporting guideline is not explicitly mentioned, but the paper follows standard CONSORT-like reporting for a clinical trial.

Evidence

direct quote[Abstract, Methods]

“Trial registration ClinicalTrials.gov NCT05631262 (https://clinicaltrials.gov/ct2/show/NCT05631262).”

direct quote[Discussion, 'Limitations of this study']

“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.”

direct quote[Funding, Competing interests]

“This study was funded by Sichuan Kelun-Biotech Biopharmaceutical... Competing interests: ...JY, YD, XJ, and JG are employed by Sichuan Kelun-Biotech Biopharmaceutical YD, XJ, and JG hold company stock.”

PASSReviewer 3· 90% conf

The paper provides a comprehensive methods description, trial registration, reports all planned outcomes (including negative subgroup results), discusses limitations, and states funding and conflicts. The only omission is failure to explicitly reference a reporting checklist (e.g., CONSORT), which is considered a minor reporting gap.

Evidence

direct quote[Abstract and Methods]

“Trial registration ClinicalTrials.gov NCT05631262”

direct quote[Discussion, Limitations of this study]

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

direct quote[Funding and Competing interests sections]

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

7 copyedit issues flagged: mostly consistency, clarity.

Checked 30 references: 29 verified — 1 unresolved.

Reproducibility

5 data/code links checked; 5 live.

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

Adcurare Rigor Action ItemsFinal pass before journal submission

Ready after moderate edits. The paper is methodologically sound but requires fixing the data/code availability (deposit code in a version-controlled repository), adding a CONSORT checklist reference, tempering one over-claim in the discussion, verifying the unresolved reference, correcting the copyedit placeholders, and providing full antibody identification before submission.

1.
HIGHreporting
Explicitly state adherence to the CONSORT 2010 statement for randomised trials and submit a completed CONSORT checklist as a supplementary file.
This is required by most journals for RCTs and verifies that all key reporting elements are covered.
2.
HIGHdata code
Deposit the analysis code in a version-controlled public repository (e.g., GitHub, Zenodo) with a persistent DOI instead of only as supplementary files.
Supplementary files are not version-controlled or citable; a repository ensures long-term accessibility and reproducibility.
3.
HIGHreporting
Temper the claim 'These findings for sac-TMT may redefine treatment standards for this population' in the Discussion to reflect that this is a Phase 2 trial and validation from ongoing Phase 3 trials is needed.
Overstating conclusions from a Phase 2 trial is a common reason for reviewer pushback and may mislead readers.
4.
HIGHother
Verify and correct the reference flagged as 'not found in the registry' (Kelun-Biotech’s TROP2-ADC SKB264 (sac-TMT) Third NDA for EGFR-mutant NSCLC Accepted by NMPA, DOI: 10.1016/s0140-6736(21) – the DOI appears truncated).
A reference that cannot be located in any registry may be fabricated or have a broken DOI, which is an integrity concern.
5.
HIGHrigor
Provide complete identification for the TROP2 monoclonal antibody (EPR20043) in the Methods section: include vendor, catalog number, RRID, and dilution used for immunohistochemistry.
Clone alone is insufficient for unambiguous identification; RRIDs are the community standard for antibody reporting.
6.
MEDIUMstatistics
Add a statement verifying the proportional hazards assumption for the Cox models (or note that the log-rank test used is robust to non-proportionality).
Explicit verification of model assumptions strengthens the statistical analysis and pre-empts reviewer questions.
7.
MEDIUMcopyedit
Remove or replace all empty parentheses '()' and '(, , )' in the Results section (Patients and Efficacy subsections) with the correct figure/table references.
Empty parentheses are placeholders that break the manuscript flow and indicate incomplete final formatting.
8.
MEDIUMcopyedit
In the Results, Efficacy subsection, specify which figure shows the best change from baseline in target lesion size at the start of the sentence, and replace the empty parentheses with correct references.
Missing figure references confuse the reader and indicate incomplete final formatting.
9.
MEDIUMcopyedit
Rephrase 'The study team did not perform or have access to efficacy analysis or summary during the trial' to 'The study team did not perform or have access to any interim efficacy analyses or summaries during the trial' for clarity.
Clarifies that interim analyses, not final analyses, are referenced, aligning with standard trial conduct.
10.
MEDIUMreporting
In the Methods or a note to Table 2, clarify the data cut-off dates: the primary analysis cut-off (6 June 2024) versus the final PFS/OS analysis cut-off (31 Dec 2024) to avoid ambiguity.
Consistency between table footnotes and text regarding data cut-off dates prevents confusion about which analysis is reported.
11.
MEDIUMreporting
Report race/ethnicity demographics explicitly (e.g., 'all patients were of Chinese ancestry') in the baseline table or Methods.
Race/ethnicity is a key generalizability factor; implicit reporting is insufficient for transparency.
12.
MEDIUMreporting
Consider reporting the exact p-value for the primary endpoint as a two-sided value or clearly state that one-sided testing was pre-specified and justified in the protocol.
One-sided p-values can be ambiguous; explicit justification reduces reviewer concern about significance inflation.
13.
LOWother
Add a brief statement on how outliers in safety or efficacy data were handled (e.g., 'no outliers were excluded from the analyses').
Addresses the missing outlier handling sub-criterion and pre-empts reviewer questions about data exclusions.

Full text (52,350 chars)Analyzed: Jul 6, 2026

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