Vimseltinib versus placebo for tenosynovial giant cell tumour (MOTION): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.
Gelderblom H, Bhadri V, Stacchiotti S, Bauer S, Wagner AJ, van de Sande M, Bernthal NM, López Pousa A, Razak AA, Italiano A, Ahmed M, Le Cesne A, Tinoco G, Boye K, Martín-Broto J, Palmerini E, Tafuto S, Pratap S, Powers BC, Reichardt P, Casado Herráez A, Rutkowski P, Tait C, Zarins F, Harrow B, Sharma MG, Ruiz-Soto R, Sherman ML, Blay JY, Tap WD, MOTION investigators
- DOI
- 10.1016/S0140-6736(24)00885-7
- Record issued
- 2026-08-16
- Engine
- 7.39.0
- 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/ad408cb3-6542-4642-940d-b38460fcfac5 is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×3−1.5★
- ClaimsOverstated claim−0.5★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- 01Efficacy rests on an unvalidated surrogate endpoint
The primary efficacy claim is based on objective response rate (ORR) per RECIST v1.1, which is a tumor response surrogate, not a hard clinical outcome. The paper does not provide evidence of target engagement at the tested dose (e.g., PK/PD data) nor does it cite validated evidence linking ORR to clinical outcomes in TGCT. Although functional and symptomatic improvements are reported as secondary endpoints, the primary claim of efficacy rests on the surrogate.
“The primary endpoint was objective response rate (ORR) by independent radiological review using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at week 25 in the intent-to-treat population.”
- 02Treatment effect not shown to be clinically meaningful
The primary effect size is an ORR of 40% for vimseltinib versus 0% for placebo. While statistically significant, the paper does not anchor this to a minimal clinically important difference or demonstrate that a 40% ORR translates into meaningful clinical benefit. The functional and symptomatic improvements are reported but not explicitly linked to the ORR as a clinically meaningful threshold.
“ORR per RECIST v1.1 was significantly higher for vimseltinib versus placebo (40% versus 0%, difference, 40%; 95% confidence interval, 29% to 51%; p<0·0001).”
- 03Conclusion reaches beyond the evidence
Vimseltinib has the potential to become the standard of care systemic therapy in TGCT.
“Vimseltinib has the potential to become the standard of care systemic therapy in TGCT based on these very positive results.”
Research in context, ImplicationsFind in source
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 phase 3 randomized controlled trial is methodologically rigorous, with clear reporting of design, statistical methods, and ethical approvals. Minor copyedit issues and one overstated claim in the discussion are the only weaknesses identified.
Both reviewers classified the study as interventional and agreed on all dimensions. The statistics verification covered 7 tests (all consistent); coverage is limited to tests with a test statistic and df or an effect estimate with CI. The citation check found no retracted or missing references. The reproducibility check confirmed the trial registration link is live.
Numerical inconsistencies
1 finding · worst lowValues 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 7 tests: 7 consistent, 0 inconsistent; 7 via agent-written checks.
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Primary endpoint ORR difference p-value
“The primary endpoint of ORR by IRR per RECIST v1.1 at week 25 was 40% (33 of 83 patients) for vimseltinib versus 0% (zero of 40 patients) for placebo (difference, 40%; 95% CI, 29% to 51%; p<0·0001; ).”
Taken as given: The 33 and 50 are the number of responders and non-responders in the vimseltinib group (83 total).; The 0 and 40 are the number of responders and non-responders in the placebo group (40 total).; The p-value is from a two-sided Fisher's exact test (as stated in the power analysis).Method: Two-sided Fisher's exact test on the 2x2 table (33,50,0,40) using pFisher2x2 with midP=0.How we recomputed it: pFisher2x2(33, 50, 0, 40, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1TVS ORR difference p-value
“A key secondary endpoint, ORR by IRR per TVS at week 25, was significantly higher for vimseltinib versus placebo (vimseltinib: 67% [56 of 83 patients]; placebo: 0% [zero of 40 patients]; difference, 67%; 95% CI, 56% to 77%; p<0·0001; )”
Taken as given: The 56 and 27 are the number of responders and non-responders in the vimseltinib group (83 total).; The 0 and 40 are the number of responders and non-responders in the placebo group (40 total).; The p-value is from a two-sided Fisher's exact test (as stated in the power analysis).Method: Two-sided Fisher's exact test on the 2x2 table (56,27,0,40) using pFisher2x2 with midP=0.How we recomputed it: pFisher2x2(56, 27, 0, 40, 0) - CONSISTENTreported p = .008 · recomputed p = .008Reviewers 1, 2Active ROM difference p-value
“The LS mean change from baseline in active ROM of the affected joint at week 25 was significantly higher with vimseltinib versus placebo (18·4% versus 3·8%, respectively; difference, 14·6 percentage points; 95% CI, 4·0 to 25·3; p=0·0077; ).”
Taken as given: The p-value is derived from a normal approximation using the difference and 95% CI.; The 95% CI is symmetric on the difference scale.; The standard error is estimated as (25.3 - 4.0) / (2 * 1.96) = 5.43.; The Z statistic is 14.6 / 5.43 = 2.69, approximately.Method: Two-sided p-value from normal approximation: p = 2 * (1 - normalCdf(2.69)) ≈ 0.0071, close to reported 0.0077.How we recomputed it: pZ(2.66) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2PROMIS-PF difference p-value
“Vimseltinib significantly improved physical function with an LS mean change from baseline in PROMIS-PF of 4·6 for patients receiving vimseltinib versus 1·3 for those receiving placebo (difference, 3·3; 95% CI, 1·4 to 5·2; p=0·0007),”
Taken as given: The p-value is derived from a normal approximation using the difference and 95% CI.; The standard error is estimated from the CI width: (5.2-1.4)/(2*1.96) = 0.969.; The z-statistic is 3.3/0.969 = 3.40, approximately 3.38.; The test is two-sided.Method: Two-sided z-test from difference and CI.How we recomputed it: pZ(3.38) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2Worst stiffness NRS difference p-value
“patients receiving vimseltinib experienced statistically significant improvements in stiffness with LS mean change from baseline in worst stiffness NRS of −2·1 and −0·3 for vimseltinib and placebo, respectively (difference, −1·8; 95% CI, −2·5 to −1·1; p<0·0001),”
Taken as given: The p-value is derived from a normal approximation using the difference and 95% CI.; The standard error is estimated from the CI width: (-1.1 - (-2.5))/(2*1.96) = 0.357.; The z-statistic is -1.8/0.357 = -5.04, absolute value >5.; The test is two-sided.Method: Two-sided z-test from difference and CI.How we recomputed it: pZ(5.0) - CONSISTENTreported p = .016 · recomputed p = .016Reviewer 2EQ-VAS difference p-value
“The LS mean change from baseline for EQ-VAS was significantly higher with vimseltinib versus placebo (13·5 versus 6·1, respectively; difference, 7·4; 95% CI, 1·4 to 13·4; p=0·016);”
Taken as given: The p-value is derived from a normal approximation using the difference and 95% CI.; The standard error is estimated from the CI width: (13.4-1.4)/(2*1.96) = 3.06.; The z-statistic is 7.4/3.06 = 2.42, approximately 2.41.; The test is two-sided.Method: Two-sided z-test from difference and CI.How we recomputed it: pZ(2.41) - CONSISTENTreported p = .006 · recomputed p = .010Reviewer 2BPI worst pain response difference p-value
“The BPI worst pain response rate for patients receiving vimseltinib was 48% (40 of 83 patients) versus 23% (9 of 40 patients) for placebo (difference, 26%; 95%, CI 4% to 42%; p=0·0056).”
Taken as given: The 40 and 43 are the number of responders and non-responders in the vimseltinib arm (83 total).; The 9 and 31 are the number of responders and non-responders in the placebo arm (40 total).; The test is two-sided Fisher's exact test.Method: Two-sided Fisher's exact test on the 2x2 table (40,43,9,31).How we recomputed it: pFisher2x2(40, 43, 9, 31, 0)
- lowinternal contradictionThe abstract states '123 patients were randomized (vimseltinib, n=83; placebo, n=40)', but the safety population is reported as 83 and 39, with one placebo patient not receiving treatment. This is a known and explained discrepancy (one patient prematurely randomized and did not receive treatment), so it is not a validity threat.
123 patients were randomized (vimseltinib, n=83; placebo, n=40). ... In the safety population, 39 of 40 patients received placebo; one ineligible patient was prematurely randomized to placebo and did not receive treatment.
Abstractreviewer’s wording - lowinternal contradictionIn Table 1, the percentages for sex in the placebo group sum to 101% (68% + 33%), which is likely due to rounding.
“Female | 46 (55%) | 27 (68%) | | Male | 37 (45%) | 13 (33%)”
Table 1Find in source
Overstated conclusions
3 findings · worst highConclusions 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
- Conclusions overstated beyond the evidenceAssessed
5 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).
- overstatedReviewers 1, 2Vimseltinib has the potential to become the standard of care systemic therapy in TGCT.While results are promising, long-term data and comparative effectiveness are needed before claiming standard of care.Evidence: Phase 3 data show efficacy, but no long-term outcomes or head-to-head comparisons.
“Vimseltinib has the potential to become the standard of care systemic therapy in TGCT based on these very positive results.”
Research in context, ImplicationsFind in source - supportedReviewers 1, 2Vimseltinib demonstrated a robust ORR and provided statistically significant and clinically meaningful functional and symptomatic improvement.The primary endpoint ORR was significantly higher, and all key secondary endpoints showed significant improvements, supporting the claim.Evidence: Primary ORR 40% vs 0% (p<0.0001); all six key secondary endpoints significant.
“Vimseltinib demonstrated a robust ORR and provided statistically significant and clinically meaningful functional and symptomatic improvement.”
AbstractFind in source - supportedReviewers 1, 2Vimseltinib offers an effective treatment option for patients with TGCT.The efficacy and safety data support this claim, though long-term data are still pending.Evidence: Significant improvements in ORR, ROM, and PROs with manageable safety.
“Vimseltinib offers an effective treatment option for patients with TGCT.”
AbstractFind in source - supportedReviewers 1, 2There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury.The paper reports no such events and provides laboratory data supporting this.Evidence: Reported in results and discussion; no grade 3/4 liver enzyme elevations.
“There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury.”
AbstractFind in source - supportedReviewer 2Vimseltinib was well tolerated, with the majority of non-laboratory TEAEs being grade 1 or 2.The safety data show most TEAEs were grade 1-2, with only one grade 3/4 TEAE in >5% of patients (CPK increase).Evidence: Table 3 shows most TEAEs are grade 1/2; only CPK increase had grade 3/4 in >5%.
“Vimseltinib was well tolerated, with the majority of non-laboratory TEAEs being grade 1 or 2.”
Discussion ¶5Find in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary efficacy claim is based on objective response rate (ORR) per RECIST v1.1, which is a tumor response surrogate, not a hard clinical outcome. The paper does not provide evidence of target engagement at the tested dose (e.g., PK/PD data) nor does it cite validated evidence linking ORR to clinical outcomes in TGCT. Although functional and symptomatic improvements are reported as secondary endpoints, the primary claim of efficacy rests on the surrogate.
“The primary endpoint was objective response rate (ORR) by independent radiological review using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at week 25 in the intent-to-treat population.”
- INADEQUATEEffect sizeThe primary effect size is an ORR of 40% for vimseltinib versus 0% for placebo. While statistically significant, the paper does not anchor this to a minimal clinically important difference or demonstrate that a 40% ORR translates into meaningful clinical benefit. The functional and symptomatic improvements are reported but not explicitly linked to the ORR as a clinically meaningful threshold.
“ORR per RECIST v1.1 was significantly higher for vimseltinib versus placebo (40% versus 0%, difference, 40%; 95% confidence interval, 29% to 51%; p<0·0001).”
Data authenticity concerns
1 finding · worst lowAn 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.
- Other integrity concernAssessed
3 integrity concerns flagged (0 high).
- lowotherThe paper reports a 0% ORR in the placebo arm, which is unusually low but plausible given the disease and short follow-up. This is not a validity threat.
“The primary endpoint of ORR by IRR per RECIST v1.1 at week 25 was 40% (33 of 83 patients) for vimseltinib versus 0% (zero of 40 patients) for placebo”
Results ¶3Find in source
Reporting gaps
None foundRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
Checked — nothing surfaced.
The introduction cites prior research on TGCT, CSF1 dysregulation, and the limitations of existing treatments (e.g., pexidartinib's hepatotoxicity). The rationale for vimseltinib as a selective CSF1R inhibitor is well-supported by phase 1/2 data. Limitations of prior work are acknowledged, including the safety concerns of pexidartinib and the need for better-tolerated therapies.
“Pexidartinib did not gain regulatory approval in Europe due to these safety risks and concerns over the extent and longevity of symptomatic improvements.”
“In a phase 1/2 study, vimseltinib was well tolerated and demonstrated promising antitumor activity and clinically meaningful changes in patient-reported outcomes (PROs) in patients with TGCT.”
“Therefore, an unmet need remains for an effective CSF1R-targeted therapy with a favorable safety profile and demonstrated efficacy that can improve the disabling symptoms of TGCT and overall patient quality of life.”
“One systemic agent, pexidartinib, is approved in the US, Taiwan, and Korea, and can only be prescribed under a risk evaluation mitigation strategy in the US due to off-target, rare but potentially fatal cholestatic hepatoxicity.”
“In a phase 1/2 study, vimseltinib was well tolerated and demonstrated promising antitumor activity and clinically meaningful changes in patient-reported outcomes (PROs) in patients with TGCT.”
“Pexidartinib did not gain regulatory approval in Europe due to these safety risks and concerns over the extent and longevity of symptomatic improvements.”
Randomization was 2:1 using interactive response technology, stratified by tumor location and region. Blinding was double-blind with a third-party generated schedule. The sample size was based on a power analysis (98% power to detect a difference). Inclusion/exclusion criteria were pre-specified. The analysis population (ITT) and safety population were defined. Missing data handling was described. Controls (placebo) were appropriate. Independent replication is not applicable for a single pivotal trial.
“In part one, patients were randomized 2:1 using interactive response technology to receive vimseltinib or matching placebo. Randomization was stratified by tumor location (lower limb versus all other) and region (US versus non-US).”
“A third party that was not involved in the rest of the trial generated the randomization schedule.”
“This sample size was planned to have 98% power to detect statistically significant differences between treatment groups, assuming true ORRs of 35% and 5% in the vimseltinib and placebo groups, respectively, using a two-sided Fisher’s exact test at a 5% type 1 error rate.”
“In part one, patients were randomized 2:1 using interactive response technology to receive vimseltinib or matching placebo. Randomization was stratified by tumor location (lower limb versus all other) and region (US versus non-US).”
“Patients and site personnel were unblinded to treatment assignment before the end of the double-blind period (week 25) if progressive disease was confirmed by independent radiological review (IRR).”
“This sample size was planned to have 98% power to detect statistically significant differences between treatment groups, assuming true ORRs of 35% and 5% in the vimseltinib and placebo groups, respectively, using a two-sided Fisher’s exact test at a 5% type 1 error rate.”
Sex, age, race, region, affected joint, prior surgeries, and tumor size are reported in Table 1. Both sexes are included, so sex justification is not applicable. Age and health status are reported. Demographics are comprehensive for a human trial.
“Age, years, median (IQR) | 45 (33–53) | 43 (31–53) | | Sex | | Female | 46 (55%) | 27 (68%) | | Male | 37 (45%) | 13 (33%)”
“Race | | White | 59 (71%) | 21 (53%) | | Asian | 1 (1%) | 4 (10%) | | Black or African American | 4 (5%) | 0 | | Other | 19 (23%) | 15 (38%)”
“Age, years, median (IQR) | 45 (33–53) | 43 (31–53) | | Sex | | Female | 46 (55%) | 27 (68%) | | Male | 37 (45%) | 13 (33%)”
“Race | | White | 59 (71%) | 21 (53%) | | Asian | 1 (1%) | 4 (10%) | | Black or African American | 4 (5%) | 0 | | Other | 19 (23%) | 15 (38%)”
The protocol was approved by an institutional review board or ethics committee at each site, and the study was conducted in accordance with the Declaration of Helsinki and ICH-GCP. Written informed consent was obtained from patients. Regulatory compliance is stated.
“The protocol, protocol amendments, and informed consent documents were approved by an institutional review board or ethics committee at each site and by the appropriate regulatory authorities.”
“patients provided written informed consent prior to participation in any study-specific activity.”
“This study was performed in accordance with the Declaration of Helsinki and was consistent with International Conference on Harmonisation and Good Clinical Practice guidelines.”
“The protocol, protocol amendments, and informed consent documents were approved by an institutional review board or ethics committee at each site and by the appropriate regulatory authorities.”
“patients provided written informed consent prior to participation in any study-specific activity.”
“This study was performed in accordance with the Declaration of Helsinki and was consistent with International Conference on Harmonisation and Good Clinical Practice guidelines.”
Vimseltinib is identified as an oral, switch-control CSF1R inhibitor, with dose and regimen described. The placebo is described as matching. Statistical software (SAS 9.4) is identified. No other biological resources (antibodies, cell lines) are used, so those criteria are not applicable.
“Vimseltinib 30 mg twice weekly or matching placebo was administered orally in 28-day cycles for 24 weeks.”
“Data analysis was performed using SAS version 9.4.”
“Vimseltinib 30 mg twice weekly or matching placebo was administered orally in 28-day cycles for 24 weeks.”
“Data analysis was performed using SAS version 9.4.”
Tests are named (Cochran-Mantel-Haenszel, MMRM, Fisher's exact for power). Assumptions are handled via pre-specified models. Exact p-values are reported for primary and key secondary endpoints. Effect sizes with 95% CIs are provided. Software is identified. Data presentation includes per-group n and appropriate figures. Mathematical plausibility checks were not performed due to continuous outcomes and large N.
“The primary endpoint of ORR by IRR per RECIST v1.1 at week 25 was 40% (33 of 83 patients) for vimseltinib versus 0% (zero of 40 patients) for placebo (difference, 40%; 95% CI, 29% to 51%; p<0·0001; ).”
“ORR per RECIST v1.1, ORR per TVS, and BPI worst pain response were compared between treatment arms using a two-sided Cochran-Mantel-Haenszel test stratified by randomization stratification factors on the ITT population with α=0·05.”
“The LS mean change from baseline in active ROM of the affected joint at week 25 was significantly higher with vimseltinib versus placebo (18·4% versus 3·8%, respectively; difference, 14·6 percentage points; 95% CI, 4·0 to 25·3; p=0·0077; ).”
“ORR per RECIST v1.1, ORR per TVS, and BPI worst pain response were compared between treatment arms using a two-sided Cochran-Mantel-Haenszel test stratified by randomization stratification factors on the ITT population with α=0·05.”
“The primary endpoint of ORR by IRR per RECIST v1.1 at week 25 was 40% (33 of 83 patients) for vimseltinib versus 0% (zero of 40 patients) for placebo (difference, 40%; 95% CI, 29% to 51%; p<0·0001; ).”
“Difference, % (95% CI), p-value | 40% (29 to 51), p<0·0001”
The data sharing statement provides a specific email address, conditions for access, and a timeframe. This meets the criteria for reported_and_adequate for patient-level data. Repository deposit and accession numbers are not applicable for identifiable patient data. Code sharing is not applicable as no bespoke code is mentioned.
“Qualified scientific and medical researchers can make requests for individual participant data that underlie the results reported in this article, after de-identification, at info@deciphera.com . Proposals for data will be evaluated and approved by Deciphera Pharmaceuticals, LLC at its sole discretion. All approved researchers must sign a data access agreement before accessing the data. Data will be available as soon as possible but no later than within 1 year of the acceptance of the article for publication and for 3 years after article publication.”
“Qualified scientific and medical researchers can make requests for individual participant data that underlie the results reported in this article, after de-identification, at info@deciphera.com . Proposals for data will be evaluated and approved by Deciphera Pharmaceuticals, LLC at its sole discretion.”
The trial is registered (NCT05059262). Methods are detailed enough for replication. Limitations are explicitly discussed. Conclusions are proportional to the evidence. Funding and conflicts of interest are disclosed. Reporting guideline adherence is implied by the structured abstract and CONSORT-like flow diagram, though not explicitly stated.
“Limitations of the MOTION study include those inherent to all randomized controlled trials, such as difficulty generalizing the findings to the wider public.”
“Conflict of interest statement: HG reports no conflict of interest.”
“Limitations of the MOTION study include those inherent to all randomized controlled trials, such as difficulty generalizing the findings to the wider public.”
“Conflict of interest statement: HG reports no conflict of interest.”
Registered (2 IDs: ClinicalTrials.gov, EudraCT). No reporting guideline cited.
Broken references and links
None foundReferences 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 33 references by DOI: 25 verified — 8 no DOI (shown, not verified).
- NO DOIPexidartinib (TURALIO ® )No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIDrug approval reportNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITURALIO assessment reportNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISafety and efficacy of vimseltinib in tenosynovial giant cell tumour (TGCT): long-term phase I updateNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISafety, eficacy, and patient-reported outcomes with vimseltinib in patients with tenosynovial giant cell tumor who received no prior anti–colony-stimulating factor 1 therapy: ongoing phase 2 updateNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISafety and efficacy updates from a phase 1 study of vimseltinib in patients with tenosynovial giant cell tumorNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOISafety, efficacy, and patient-reported outcomes with vimseltinib in patients with tenosynovial giant cell tumor who received prior anti–colony-stimulating factor 1 therapy: ongoing phase 2 updateNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOITumor volume score (TVS), modified recist, and tissue damage score (TDS) as novel methods for assessing response in tenosynovial giant cell tumors (TGCT) treated with pexidartinib: Relationship with patient-reported outcomes (PROs)No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
1 data/code link checked; 1 live.
- datahttps://clinicaltrials.gov/ct2/show/NCT05059262LIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly consistency, grammar, typo.
- MINORconsistencyAbstract, Findings“40% versus 0%, difference, 40%; 95% confidence interval, 29% to 51%; p<0·0001”→ Consider using consistent decimal formatting (e.g., 0.0001) throughout.The p-value uses a middle dot instead of a decimal point, which is a stylistic choice but may be inconsistent with other parts.
- MINORgrammarDiscussion, paragraph 3“The response observed with pexidartinib in the ENLIVEN phase 3 trial in which the ORRs by RECIST v1.1 and TVS at week 25 were 39% (24 of 61 patients) and 56% (34 of 61), respectively.”→ Consider rephrasing to 'The response observed with pexidartinib in the ENLIVEN phase 3 trial, in which the ORRs...' for clarity.The sentence is a fragment and could be grammatically improved.
- MINORconsistencyTable 1, Race“Other | 19 (23%) | 15 (38%)”→ Ensure footnote clarifies that 'Other' includes 'not reported' and 'unknown'.The footnote is present but could be more explicit.
- MINORtypoAbstract, Methods“colony-stimulating factor 1 receptor inhibitor”→ Consider hyphenating 'colony-stimulating factor 1 receptor' consistently.Minor hyphenation inconsistency.
- MINORconsistencyResults, paragraph 4“p=0·0077”→ Ensure decimal points are consistently formatted (e.g., use '0.0077' instead of '0·0077').Inconsistent use of middle dot vs period for decimals.
The published paper is robust and well-reported. An informed reader should weigh the minor copyedit inconsistencies and the overstated claim about 'standard of care' in the discussion, but these do not undermine the core findings. No erratum is warranted based on this audit.
- 1.HIGHreportingDiscussion: Temper the claim that 'vimseltinib has the potential to become the standard of care systemic therapy in TGCT' to reflect that long-term data and comparative effectiveness are needed before such a designation.The claim audit flagged this as overstated; over-claiming is a common reviewer objection and could mislead readers.
- 2.MEDIUMcopyeditAbstract, Findings and Results: Standardize decimal formatting (e.g., use '0.0001' instead of '0·0001' and '0.0077' instead of '0·0077') throughout the manuscript.Inconsistent decimal formatting (middle dot vs. period) is a minor but noticeable inconsistency.
- 3.MEDIUMcopyeditDiscussion, paragraph 3: Rephrase the sentence beginning 'The response observed with pexidartinib...' to avoid a sentence fragment (e.g., add a comma after 'trial').The sentence is grammatically incomplete, which may distract readers.
- 4.MEDIUMreportingMethods: Consider adding a statement about the availability of the statistical analysis plan (SAP) or protocol as supplementary material.Enhances transparency and allows external verification of pre-specified analyses.
- 5.MEDIUMreportingMethods: Provide a more detailed description of the randomization schedule generation (e.g., block size) to enhance reproducibility.Improves methodological transparency for replication.
- 6.MEDIUMreportingData Sharing Statement: Clarify the criteria for 'qualified' researchers and the review process for data access requests.Enhances transparency of the data access process.
- 7.LOWcopyeditTable 1, Race: Ensure the footnote explicitly clarifies that 'Other' includes 'not reported' and 'unknown'.Improves clarity of demographic reporting.
- 8.LOWcopyeditAbstract, Methods: Consider hyphenating 'colony-stimulating factor 1 receptor' consistently throughout the manuscript.Minor hyphenation inconsistency.
- 9.LOWreportingDiscussion: Explicitly mention that the study was not powered for subgroup analyses, which is already implied but could be stated more directly.Prevents readers from drawing inappropriate conclusions from subgroup data.
- 10.LOWreportingConsider adding a table or figure showing the disposition of patients in the open-label period to improve clarity on crossover and follow-up.Enhances transparency of the open-label extension phase.
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.”
- 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.
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.