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

Emerging evidence implicates the gut microbiome in modulating ICI efficacy.

越来越多的证据表明肠道微生物群在调节ICI疗效方面起着作用。

In the investigator-initiated, randomized, double-blindplacebo-controlledphase 2a TACITO trial, we evaluated whether fecal microbiota transplantation (FMT) from complete ICI responders enhances clinical outcomes in treatment-naive patients with metastatic RCC (mRCC) receiving pembrolizumab + axitinib.

在一项由研究者发起的、随机的、双盲安慰剂对照的2a期TACITO试验中，我们评估了来自完全ICI反应者的粪便微生物群移植（FMT）是否能增强接受pembrolizumab+axitinib治疗的未经治疗的转移性肾细胞癌（mRCC）患者的临床结果。

The primary endpoint was the rate of patients free from disease progression at 12 months after randomization (12-month progression-free survival(PFS)).

主要终点是随机化后12个月无疾病进展的患者比例（12个月无进展生存率（PFS））。

Secondary endpoints were median PFS and median overall survival, objective response rate(ORR), safety and microbiome changes, after randomization.

次要终点包括随机化后的中位无进展生存期和中位总生存期、客观缓解率（ORR）、安全性和微生物组变化。

Forty-five patients randomly received donor FMT (d-FMT) or placebo FMT (p-FMT).

45名患者随机接受了供体粪便微生物移植（d-FMT）或安慰剂粪便微生物移植（p-FMT）。

Although the primary endpoint was not met (70% versus 41% for d-FMT versus p-FMT, respectively, P = 0.053), the secondary endpoint of median PFS was significantly longer with d-FMT (24.0 months in the d-FMT arm versus 9.0 months in the p-FMT arm; hazard ratio= 0.50, P = 0.035).

尽管主要终点未达到（d-FMT与p-FMT分别为70%和41%，P = 0.053），但次要终点的中位无进展生存期（PFS）在d-FMT组显著更长（d-FMT组为24.0个月，p-FMT组为9.0个月；风险比为0.50，P = 0.035）。

The ORR was 52% of patients in the d-FMT arm and 32% of patients receiving placebo.

d-FMT组患者的客观缓解率（ORR）为52%，而接受安慰剂的患者为32%。

Microbiome analysis confirmed donor strain engraftment and increased α-diversity and larger microbiome shifts (β-diversity) compared with baseline composition in the d-FMT treatment group.

微生物组分析确认了供体菌株在粪便微生物群移植（d-FMT）治疗组中的定植，并与基线组成相比增加了α多样性以及更大的微生物群变化（β多样性）。

Acquisition or loss of specific strains, but not total engraftment, was associated with the primary endpoint.

特定菌株的获得或丧失，而非总体定植，与主要终点相关。

Our findings support the safety and potential efficacy of selected donor FMT to enhance ICI-based treatment in mRCC, which deserves further investigations.

我们的发现支持选择性供体粪便微生物群移植(FMT)增强基于ICI的mRCC治疗的安全性和潜在疗效，值得进一步研究。

ClinicalTrials.gov identifier: NCT04758507 .

ClinicalTrials.gov注册号：NCT04758507。