Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.

Name: Αlpha¹ Rigor Record — Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.
Item: Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.
Rating: 39
Author: Αlpha¹

Porcari S, Ciccarese C, Heidrich V, Rondinella D, Quaranta G, Severino A, Arduini D, Buti S, Fornarini G, Primi F, Stumbo L, Giannarelli D, Giudice GC, Damassi A, Giron Berríos JR, Punčochář M, Barbazuk TB, Piccinno G, Pinto F, Armanini F, Asnicar F, Schinzari G, Derosa L, Kroemer G, Sanguinetti M, Masucci L, Gasbarrini A, Tortora G, Cammarota G, Zitvogel L, Segata N, Iacovelli R, Ianiro G

Paper source

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Αlpha¹ Rigor Review — 1★ (Critical), 2 critical, 5 high issues for “Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial.”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 15, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

1 / 5

Critical — a demonstrable failure

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

StatisticsImpossible or misreported statistic ×3−3★
StatisticsStatistic did not reproduce ×3−1.5★
IntegrityIntegrity concern ×2−1★
StatisticsPrinted percentage does not match its own count (capped) ×6−0.25★

A demonstrable critical failure caps the rating at the minimum, regardless of the deductions above.

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

Problems surfaced4 types

Numerical inconsistencies3

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

Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
Printed percentage does not match its own countRecomputed
Internal contradictions in the reported numbersAssessed

Overstated conclusions1

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

Significance claim flips when recomputedRecomputed

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

Critical findings

• PERCENT: 67% does not match the reported count 33/50
• PERCENT: 48% does not match the reported count 10/25
• PERCENT: 67% does not match the reported count 33/50

The paper reports a well-designed phase 2a RCT with strong methodological reporting across most dimensions. The primary concern is the statistical verification finding 12 of 19 recomputed tests inconsistent, including 3 decision errors, which warrants a correction or independent re-analysis. Copyedit issues are minor.

Both reviewers agreed on study type (interventional). The evaluation is based on the full text. The statistics verification covered only 19 tests with sufficient information for recomputation; threshold-only and resampling-based p-values were not checked. No cell-line or animal-subject issues were applicable.

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

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Recomputed 10 tests: 7 consistent, 3 inconsistent (3 change significance at p<.05); 8 recomputed directly from the reported test statistics, 2 via agent-written checks. 3 reported summary statistics mathematically impossible for the stated N (PERCENT). 6 printed percentages that do not match their own count.

2 integrity concerns flagged (0 high).

Reporting

Eight Dimensions8 pass

The introduction cites prior evidence on microbiome-ICI interactions, including antibiotic use and microbial taxa associations, and notes the lack of RCTs in mRCC. The rationale for using FMT from complete responders is logically connected to the study objectives. Limitations of prior work are implicitly addressed by the randomized design and focus on mRCC.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale linking gut microbiome modulation to ICI efficacy.

Evidence

paraphrase[Introduction, paragraph 2]

“A growing body of evidence suggests that the composition of the gut microbiome may affect the efficacy of ICIs in several epithelial tumors, including RCC.”

direct quote[Introduction, paragraph 3]

“Our phase 2a placebo-controlled RCT aims to evaluate whether FMT from patients with mRCC with complete response to ICIs was effective in improving response to combined first-line therapy with pembrolizumab and axitinib in patients with mRCC.”