Rigor Reviewed

Rigor-Reviewed Manuscript

Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial.

Name: Adcurare Rigor Record — Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial.
Item: Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial.
Rating: 59
Author: Adcurare

Wainberg ZA, Manji GA, Bahary N, Ulahannan SV, Pant S, Spigel DR, Uboha NV, Oberstein PE, Saeed A, Beagle B, Kim JY, Wang N, Weeder B, Shitole S, Mrouj K, Scott JR, Ensign LG, DiRenzo DM, Walters MJ, Wu W, Kaplan A, Cho S, Kabbarah O, O'Reilly EM

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Adcurare Rigor Review — 2.5★ (Weak), 0 critical, 10 high issues for “Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 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

2.5 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×3−1.5★
ReportingStudy design partially met−0.25★
ReportingStatistical analysis partially met−0.25★
ReportingData & code availability partially met−0.25★
ReportingReporting transparency partially met−0.25★

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.6.0Source: full text

Problems surfaced7 types

Statistical reporting gaps (tests, assumptions, effect sizes)
Data/code availability incomplete
Reporting/transparency gaps
Study-design details incomplete (controls, blinding, power)
Data look implausibly clean
Methods and results do not match
Other integrity concern

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.

The manuscript presents a phase 1b trial with a well-founded scientific premise, adequate demographic reporting, and transparent limitations. However, it fails to identify key resources (antibodies, cell line authentication, software) and has gaps in ethics committee naming, data/code deposition, and formal design elements like power analysis and outlier handling.

All eight dimensions were applicable and scored. The reviewers diverged on ethical approvals (pass vs. warn), key resources (pass vs. fail), and statistical analysis (pass vs. warn); evidence favoring the more conservative rating was adopted in each case. Verification components found no statistical errors, no retracted/not-found references, and no high-severity integrity concerns.

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

Recomputed 8 tests: 8 consistent, 0 inconsistent, 8 via agent-written checks.

3 integrity concerns flagged (0 high).

Reporting

Eight Dimensions4 pass · 4 warn

The paper cites prior research on CD73, adenosine, and PDAC, noting that multiple phase 3 trials have failed. It provides a logical rationale linking CD73 inhibition to reduction of immunosuppressive adenosine and improvement of immune function. It also explicitly addresses limitations of prior transcriptional signatures, stating they have limited predictive value.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The scientific premise is well-established with cited prior research, a clear rationale, and acknowledged limitations of previous work.

Evidence

direct quote[Introduction, paragraph 3]

“Multiple phase 3 trials of new therapeutic modalities have failed to improve on the standard care for mPDAC.”

direct quote[Introduction, paragraph 2]

“The ectonucleotidase CD73 is a key enzyme involved in the production of extracellular adenosine from adenosine triphosphate (ATP).”

direct quote[Introduction, paragraph 3]

“However, these transcriptional signatures have limited predictive value, in part because they may not adequately reflect the cellular heterogeneity in the TME.”

PASSReviewer 2· 90% conf

The scientific premise is well-established. Prior work on CD73 and adenosine in the tumor microenvironment is cited, the rationale linking CD73 inhibition to clinical benefit in PDAC is clearly laid out, and the limitations of prior transcriptional signatures are acknowledged and addressed.

Evidence

direct quote[Introduction, paragraph 1-2]

“The ectonucleotidase CD73 is a key enzyme involved in the production of extracellular adenosine from adenosine triphosphate (ATP). Adenosine signaling protects healthy tissue from immune system activity, promotes angiogenesis and enhances wound healing.”

direct quote[Introduction, paragraph 3]

“However, these transcriptional signatures have limited predictive value, in part because they may not adequately reflect the cellular heterogeneity in the TME.”

paraphrase[Introduction, last paragraph]

“The study aimed to evaluate the safety and tolerability of quemliclustat combined with G/nP with or without zimberelimab and to conduct post-hoc biomarker analyses linking clinical benefit to adenosine biology.”

PASSReviewer 3· 95% conf

The scientific premise is well-established: the paper cites prior work on CD73/adenosine biology in cancer and the unmet need in PDAC, provides a clear rationale for targeting CD73, and acknowledges limitations of prior approaches.

Evidence

direct quote[Introduction, paragraphs 1-3]

“Multiple phase 3 trials of new therapeutic modalities have failed to improve on the standard care for mPDAC...The ectonucleotidase CD73 is a key enzyme involved in the production of extracellular adenosine from adenosine triphosphate (ATP).”

direct quote[Introduction, paragraph 3]

“However, these transcriptional signatures have limited predictive value, in part because they may not adequately reflect the cellular heterogeneity in the TME.”

direct quote[Introduction, paragraph 4]

“In the ARC-8 phase 1b study, we evaluated the safety and tolerability of quemliclustat combined with standard-of-care G/nP with or without the anti-PD-1 antibody zimberelimab, in patients with treatment-naive mPDAC.”

Randomization method (permuted block) and unit (patient) are reported. The open-label design is stated but without a rationale for lack of blinding. No formal power analysis was performed; the sample size justification is estimation-based. Inclusion/exclusion criteria are clearly defined. No outlier handling or missing-data approach is described.

Sub-criteria

controlsN/A

power analysisINADEQUATE

blinding levelsINADEQUATE

outlier handlingNOT REPORTED

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

The study design is adequately described for a phase 1b trial, but key elements such as blinding rationale, formal power analysis, and outlier handling are missing.

Evidence

direct quote[Methods, Dose-expansion phase, paragraph 2]

“enrolled and randomized 2:1 using the permuted block method”

direct quote[Results, paragraph 1]

“ARC-8 is an ongoing, phase 1b, open-label, dose-escalation and dose-expansion study”

direct quote[Methods, Statistical analysis, paragraph 1]

“The sample size justification was based on an estimation framework, and the study was designed for descriptive statistical analysis rather than formal statistical hypothesis testing involving power and type I error considerations.”

WARNReviewer 2· 85% conf

As a phase 1b open-label trial, several design rigor elements (blinding, formal power analysis, pre-specified inclusion/exclusion with full detail) are not fully addressed. The randomization method is stated, but the lack of blinding and the absence of a concurrent randomized control arm are key limitations.

Evidence

direct quote[Methods, Dose-expansion phase]

“...patients were enrolled and randomized 2:1 using the permuted block method to receive the quemliclustat RP2D combined with G/nP with or without zimberelimab.”

direct quote[Results, first paragraph]

“ARC-8 (NCT04104672) is an ongoing, phase 1b, open-label, dose-escalation and dose-expansion study...”

direct quote[Methods, Statistical analysis]

WARNReviewer 3· 90% conf

The study is a phase 1b open-label trial with a dose-escalation (3+3) and dose-expansion phase. Randomization (2:1, permuted block) was used only for the expansion arms. Key deficiencies: no blinding, no a priori power analysis for formal hypothesis testing, and the analysis is described as descriptive.

Evidence

direct quote[Methods, Dose-expansion phase]

“patients were enrolled and randomized 2:1 using the permuted block method to receive the quemliclustat RP2D combined with G/nP with or without zimberelimab.”

direct quote[Results, first paragraph]

“ARC-8 (NCT04104672) is an ongoing, phase 1b, open-label, dose-escalation and dose-expansion study”

direct quote[Methods, Statistical analysis]

Table 1 provides detailed demographics including age, sex, race, ECOG PS, liver metastases, prior therapy, and time since diagnosis. Both sexes are represented. Sex is self-reported as a binary variable.

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

Sex, age, and health status (ECOG PS) are reported; weight is not reported, but the overall reporting is adequate for a human clinical trial.

Evidence

direct quote[Table 1]

“Sex, n (%) | Male | 2 (50) | 4 (67) | 2 (67) | 3 (50) | 1 (33) | 12 (55) | | Female | 2 (50) | 2 (33) | 1 (33) | 3 (50) | 2 (67) | 10 (45) |”

direct quote[Results, Dose-escalation phase, paragraph 1]

“The median age (range) was 65 years (48–77)”

direct quote[Table 1]

“Race, n (%) | White | 4 (100) | 4 (67) | 2 (67) | 4 (67) | 2 (67) | 16 (73) |”

PASSReviewer 2· 95% conf

Patient demographics (age, sex, race, ECOG PS, baseline characteristics) are comprehensively reported in a dedicated table. Sex is reported, and since both sexes are enrolled, a single-sex justification is not required. Other biological variables (species/strain, housing) are not applicable for this human clinical trial.

Evidence

direct quote[Table 1]

“Table 1 Patient demographics and characteristics”

direct quote[Methods, Patients]

“Sex was recorded as a binary variable based on self-reported biological characteristics.”

PASSReviewer 3· 95% conf

Key biological variables (age, sex, race, ECOG PS) are reported in Table 1 for all cohorts. Sex is reported but not stratified or justified (both sexes were enrolled, so no single-sex justification needed). Species/strain/housing are not applicable for a human trial. Demographics are adequately reported.

Evidence

direct quote[Table 1]

“Age, years, median (range) | 65 (48–77) ... Sex, n (%) | Male ... Female ... Race, n (%) | White ... Asian ... Not reported”

direct quote[Methods, Patients]

“Sex was recorded as a binary variable based on self-reported biological characteristics...No analyses stratified by sex were conducted.”

The methods explicitly state that the study was conducted in conformance with the Declaration of Helsinki, CIOMS guidelines, and local IRB regulations. The protocol was approved by the local ethics committee at each site (referenced to Supplementary Table). Written informed consent was obtained from all patients.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 95% conf

Ethical compliance is reported but the ethics committee is not named in the main text, and no protocol number is provided.

Evidence

direct quote[Methods, Study design, paragraph 2]

“The study protocol was approved by the local ethics committee at each site (Supplementary Table).”

direct quote[Methods, Study design, paragraph 2]

“All patients provided written informed consent before any study procedures”

direct quote[Methods, Study design, paragraph 2]

“The study was conducted in full conformance with the Declaration of Helsinki, the Council for International Organizations of Medical Sciences International Ethical Guidelines, institutional review board regulations and all other applicable local regulations.”

PASSReviewer 2· 95% conf

The study reports compliance with the Declaration of Helsinki, local ethics committee approval (referenced to a supplementary table), and written informed consent from all patients. These meet the criteria for an adequate ethics statement.

Evidence

direct quote[Methods, Study design]

“All patients provided written informed consent before any study procedures...”

direct quote[Abstract]

“ClinicalTrials.gov identifier: NCT04104672”

PASSReviewer 3· 95% conf

Ethical approvals are adequately reported: the study conforms to the Declaration of Helsinki and other regulations, the protocol was approved by local ethics committees, and all patients provided written informed consent. A clinical trial registration number is provided.

Evidence

direct quote[Methods, Study design]

“All patients provided written informed consent before any study procedures, and patients were not compensated monetarily for participation in this trial.”

The investigational drugs (quemliclustat, zimberelimab, gemcitabine, nab-paclitaxel) are named with doses and administration schedules. The manufacturer of the drugs is not explicitly stated in the main text (e.g., 'Arcus Biosciences' for quemliclustat/zimberelimab is implied by author affiliations). Software for clinical data analysis (e.g., SAS, R) is not identified; the methods mention 'Clinical Data Interchange Consortium Study Data Tabulation Model' but no specific statistical software versions. For biomarker analyses, the paper mentions RNA-seq and ISH but does not specify software versions. Antibodies/cell lines/mycoplasma are not applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 85% conf

Key biological and chemical resources are inadequately identified: investigational products lack manufacturer details, cell lines and antibodies used in biomarker analyses are not authenticated or identified, and software is not specified.

Evidence

absence[Methods, Spatial analyses (not explicitly detailed in main text)]

Antibodies used in ISH and mIF are not identified with vendor or catalog number.

direct quote[Results, NR4A family expression is upregulated by adenosine, paragraph 1]

“pancreatic cancer cell lines MIA PaCa-2 and PANC-1”

direct quote[Methods, Dose-escalation phase, paragraph 3]

“Patients received quemliclustat intravenously (25 mg, 50 mg, 75 mg, 100 mg or 125 mg) every 2 weeks, G/nP (gemcitabine 1,000 mg m − 2 and nab-paclitaxel 125 mg m − 2 ) intravenously on days 1, 8 and 15 of a 28-day cycle and zimberelimab 240 mg intravenously every 2 weeks.”

PASSReviewer 2· 85% conf

The investigational medicinal products (quemliclustat, zimberelimab, gemcitabine, nab-paclitaxel) are adequately identified with dosing regimens. Antibodies, cell lines, and standard lab reagents are not used in the core trial; the analysis (e.g., RNA-seq, ISH) uses commercial software and assays, which are identified. The software tools used for analysis are not all versioned, but the key resources for the trial itself are adequately reported.

Evidence

direct quote[Methods, Dose-escalation phase]

“Patients received quemliclustat intravenously (25 mg, 50 mg, 75 mg, 100 mg or 125 mg) every 2 weeks, G/nP (gemcitabine 1,000 mg m−2 and nab-paclitaxel 125 mg m−2) intravenously on days 1, 8 and 15 of a 28-day cycle and zimberelimab 240 mg intravenously every 2 weeks.”

direct quote[Results, NR4A family expression...]

“...pancreatic cancer cell lines MIA PaCa-2 and PANC-1. ... colon cancer cell line HCT-116 and lung cancer cell line NCI-H650.”

direct quote[Methods, SCA analysis]

“Historical clinical trial patient-level data for the SCA were sourced from electronic data capture available through an optional data-sharing program (Medidata Solutions, Inc., a Dassault Systèmes company).”

PASSReviewer 3· 90% conf

The investigational products (quemliclustat, zimberelimab, gemcitabine, nab-paclitaxel) are identified with manufacturers/doses; software tools used in the trial are not specified in the main methods (e.g., analysis software version), but the data availability section mentions Medidata standards. Software tools for biomarker analyses (e.g., RNA-seq tools) are not listed in the truncated text.

Evidence

direct quote[Methods, Dose-escalation phase]

“Patients received quemliclustat intravenously (25 mg, 50 mg, 75 mg, 100 mg or 125 mg) every 2 weeks, G/nP (gemcitabine 1,000 mg m−2 and nab-paclitaxel 125 mg m−2) intravenously on days 1, 8 and 15 of a 28-day cycle and zimberelimab 240 mg intravenously every 2 weeks.”

absence[Methods, Statistical analysis]

Statistical analysis software not named.

Tests are named. Exact p-values are reported for key comparisons (e.g., OS comparison with SCA: P = 0.003). Effect sizes (HR) and CIs are reported. Software is not versioned in the main text. Data is presented with Kaplan-Meier curves and CIs. The analysis is correctly described as descriptive.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Statistical tests are named, exact p-values and effect sizes with CIs are reported, and data presentation is appropriate for a clinical trial. Software is not identified, but assumptions are handled by design.

Evidence

direct quote[Methods, Statistical analysis, paragraph 2]

“OS and PFS were estimated using Kaplan−Meier methodology. Median time to event for OS and PFS with two-sided 95% CIs was estimated using the Brookmeyer−Crowley method.”

direct quote[Results, Baseline tumor NR4A family expression, paragraph 2]

“hazard ratio = 0.42 (95% CI: 0.23–0.76); P = 0.0034”

absence[Methods, Statistical analysis]

Statistical software is not identified.

WARNReviewer 2· 85% conf

Statistical tests are named (e.g., Clopper-Pearson for CI, Kaplan-Meier, log-rank, Cox proportional hazards). Exact p-values are often reported (e.g., P=0.003, P=0.0238), but some comparisons use CIs without p-values. Effect sizes (HR) with 95% CIs are routinely reported. The statistical software is not specifically named (e.g., R, SAS version). Data presentation includes Kaplan-Meier curves and tables with confidence intervals. Mathematical plausibility checks are not possible for most continuous time-to-event endpoints.

Evidence

direct quote[Results, Post hoc... synthetic control arm comparison]

“Median OS was significantly longer in the Quemli100 arm (15.7 months (95% CI: 12.4–20.9)) versus the SCA (9.8 months (95% CI: 7.8–11.4)) (P = 0.003).”

direct quote[Results, Baseline tumor NR4A...]

“NR4A family expression significantly correlated with survival benefit in the BEP (PFS: hazard ratio = 0.732 (95% CI: 0.56–0.96); P = 0.0238; OS: hazard ratio = 0.678 (95% CI: 0.49–0.95); P = 0.0239).”

absence[Methods, Statistical analysis]

No statistical software version is reported.

WARNReviewer 3· 85% conf

Statistical tests are named, exact p-values are often reported, and effect sizes with CIs are provided. However, test assumptions are not mentioned (e.g., normality checks), no correction for multiplicity in exploratory analyses is stated, and the study's descriptive nature means no formal hypothesis testing was pre-specified.

Evidence

direct quote[Results, post hoc analysis]

“The median OS was 26.1 months for the NR4A high group compared to 12.4 months for the NR4A low group...hazard ratio = 0.41 (95% CI: 0.20–0.86); P = 0.015”

absence[Methods, Statistical analysis]

No mention of verifying model assumptions.

absence[Methods, Statistical analysis]

Statistical software not identified.

The data availability statement describes a managed-access platform for clinical trial data. However, RNA-seq data from biomarker analyses are not deposited in a public repository, and no accession numbers are provided. Custom code is not shared.

Sub-criteria

code sharingNOT REPORTED

accession numbersNOT REPORTED

repository depositNOT REPORTED

data availability statementADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 90% conf

A data availability statement is provided with a controlled access mechanism, but sequencing data (RNA-seq) are not deposited, and no code is shared.

Evidence

direct quote[Data availability section]

“Arcus Biosciences is committed to sharing clinical trial data with external qualified scientific researchers in the interest of advancing public health. Arcus Biosciences will provide access to individual deidentified participant data and related study documents (protocols, statistical analysis plans and clinical study reports) upon request from qualified researchers and subject to certain criteria, conditions and exceptions. For information on the process or to submit a request, visit https://trials.arcusbio.com/our-transparency-policy”

absence[Data availability section]

No repository deposit or accession numbers for RNA-seq data.

absence[Data availability section]

No code sharing statement.

WARNReviewer 2· 90% conf

A data availability statement is present describing a managed-access process via the sponsor's transparency policy, which is adequate for individual patient data. No raw sequencing data or custom code has been deposited in a public repository (e.g., GEO for RNA-seq), which is a gap for the genomic data generated.

Evidence

direct quote[Data availability]

“Arcus Biosciences will provide access to individual deidentified participant data and related study documents (protocols, statistical analysis plans and clinical study reports) upon request from qualified researchers and subject to certain criteria, conditions and exceptions.”

absence[Data availability]

RNA-seq and other genomic data are not deposited in a public repository; no accession numbers are given.

absence[Data availability]

No custom code repository is mentioned.

WARNReviewer 3· 90% conf

A data availability statement is present, describing a process for requesting deidentified participant data from the sponsor. This is adequate for a clinical trial. However, no accession numbers for sequencing data or code sharing information is provided.

Evidence

direct quote[Data availability section]

absence[Data availability section]

No accession numbers for sequencing data.

absence[Data availability section]

No code sharing statement.

Trial registration is provided. Limitations are discussed: 'The findings from ARC-8 may not be generalizable to the broader patient population...There was no concurrent, randomized control group.' Conclusions are careful: 'supports further development of quemliclustat' rather than claiming definitive efficacy. No CONSORT or ARRIVE checklist is mentioned; a CONSORT flow diagram is present (Figure 1). All pre-specified primary and secondary endpoints are reported; biomarker analyses are transparently labeled as post hoc. Funding (Arcus Biosciences) and COI declarations are extensive.

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

Reporting is largely transparent with trial registration, methods detail, limitations discussion, and proportional conclusions. However, not all secondary endpoints are reported, and no reporting guideline is referenced.

Evidence

direct quote[Abstract, Methods, Study design]

“ClinicalTrials.gov identifier: NCT04104672”

direct quote[Methods, Study design, paragraph 1]

“Additional planned secondary endpoints not reported in this paper are plasma concentration and pharmacokinetic parameters for quemliclustat, serum concentration and pharmacokinetic parameters for zimberelimab and number and percentage of patients who develop antidrug antibodies to zimberelimab.”

direct quote[Discussion, paragraph 5]

“The findings from ARC-8 may not be generalizable to the broader patient population, despite the sample size being large for an early phase trial. There was no concurrent, randomized control group.”

WARNReviewer 2· 85% conf

Methods are comprehensive for a phase 1b trial. The study is registered (NCT04104672). No formal reporting guideline (CONSORT, etc.) is referenced. All pre-specified primary and secondary outcomes are reported, though the analysis of secondary endpoints (pharmacokinetics, immunogenicity) is stated as not reported here. Limitations are discussed in the Discussion. Conclusions are generally proportional, though the post-hoc predictive biomarker claims should be interpreted cautiously. Funding and COI are declared.

Evidence

direct quote[Abstract, Methods]

“ClinicalTrials.gov identifier: NCT04104672”

direct quote[Methods, Study design]

direct quote[Discussion, last paragraph]

“As a phase 1b trial, the ARC-8 study was designed to evaluate the safety and tolerability of quemliclustat combined with G/nP with or without zimberelimab. The findings from ARC-8 may not be generalizable to the broader patient population, despite the sample size being large for an early phase trial. There was no concurrent, randomized control group.”

WARNReviewer 3· 90% conf

The study is registered (NCT04104672), limitations are discussed, and conclusions are proportional. However, no reporting guideline (e.g., CONSORT) is explicitly referenced; all outcomes are reported (primary safety, secondary efficacy), but the post hoc nature of the biomarker analysis is transparent. Conflicts of interest and funding are disclosed.

Evidence

direct quote[Abstract and Methods]

“ClinicalTrials.gov identifier: NCT04104672”

direct quote[Discussion, paragraph 5]

absence[Methods]

No reporting guideline mentioned.

8 copyedit issues flagged: mostly consistency, clarity, typo.

Checked 65 references: 62 verified — 3 not checked.

Reproducibility

6 data/code links checked; 6 live.

Registered (2 IDs: ClinicalTrials.gov). No reporting guideline cited.

Adcurare Rigor Action ItemsFinal pass before journal submission

The manuscript requires substantive revision before submission, primarily to address the key resources fail (provider missing cell line authentication, antibody identifiers, and software version) and the ethics committee naming gap. Data/code deposition and study design details (blinding rationale, outlier handling) should also be addressed. The core clinical results appear sound based on the verification checks.

1.
HIGHrigor
Report manufacturer, catalog numbers, and lot numbers for all investigational drugs (quemliclustat, gemcitabine, nab-paclitaxel, zimberelimab) in the Methods (Drug preparation section).
Current text only gives drug names and doses; reviewers require source identification for reproducibility.
2.
HIGHrigor
Provide authentication details (e.g., STR profiling) and mycoplasma testing results for all cell lines used (MIA PaCa-2, PANC-1, HCT-116, NCI-H650) in the Methods (Cell culture section).
Lack of authentication is a common reproducibility issue; journals increasingly require this information.
3.
HIGHrigor
Identify all antibodies used in ISH and mIF assays with vendor, catalog number, clone, and dilution in the Methods (Spatial analysis section).
Without antibody identifiers, the biomarker analyses cannot be reproduced.
4.
HIGHdata code
Deposit RNA-seq and spatial transcriptomics data in a public repository (e.g., GEO) and provide accession numbers in the Data Availability section.
The paper's biomarker conclusions rely on these data; deposition is required for transparency and reproducibility.
5.
HIGHethics
List the approving ethics committee(s)/IRB name(s) and protocol number(s) in the main text (Methods, Study design) rather than only in a supplementary table.
A cross-reference to a supplement for the ethics committee name is insufficient per standard reporting guidelines.
6.
HIGHstatistics
Name the statistical software (e.g., R version 4.x, SAS 9.4) and describe the procedure for verifying proportional hazards assumptions for Cox models in the Statistical Analysis section.
Software version and assumption checks are standard expectations for statistical reporting.
7.
HIGHreporting
Reference the CONSORT reporting guideline for clinical trials and provide the completed checklist as supplementary material.
Adherence to CONSORT is expected for trial reports; its absence could delay or complicate review.
8.
HIGHreporting
Share custom analysis code (e.g., R scripts for NR4A signature calculation, propensity score matching) in a public repository (GitHub/Zenodo) with a persistent DOI in the Data Availability section.
Custom code is necessary to evaluate the biomarker and SCA analyses; its absence reduces reproducibility.
9.
HIGHrigor
Add a statement in the Study Design section explaining the rationale for the open-label design and discuss its potential impact on investigator-assessed endpoints such as response rate.
Open-label design is acceptable but the rationale and potential bias should be transparent.
10.
HIGHrigor
Describe the handling of outliers and missing data for safety and efficacy analyses in the Statistical Analysis section.
Outliers and missing data can influence results; the current Methods do not address this.
11.
MEDIUMcopyedit
Standardize the abbreviation for the 100 mg quemliclustat arm throughout the manuscript (e.g., consistently use 'Quemli100' or 'quemliclustat 100 mg').
Inconsistent use (e.g., 'Quemli100' vs 'Quemli 100') may confuse readers.
12.
MEDIUMcopyedit
Ensure figure references are consistently formatted (e.g., 'Fig. 1' in text and 'Figure 1' in captions, not both).
Minor formatting inconsistency but can be flagged during peer review.
13.
LOWreporting
Explicitly state in the Statistical Analysis section that no multiplicity correction was applied to the numerous post hoc exploratory analyses (e.g., NR4A best cut, subgroup analyses), or clarify that these are purely descriptive.
Multiplicity is a common concern; transparency about handling reduces potential criticism.
14.
LOWreporting
Ensure the CONSORT flow diagram (Figure 1) legend defines all abbreviations (RP2D, PD, etc.) and explains the patient flow succinctly.
Legends should be self-contained for accessibility.

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Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial.

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Journal

DOI

10.1038/s41591-026-04283-z

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