LBA77 - Fecal microbiota transplantation (FMT) versus placebo in patients receiving pembrolizumab plus axitinib for metastatic renal cell carcinoma: Preliminary results of the randomized phase II TACITO trial

Background

Combinations of VEGFR-TKIs plus immune checkpoint inhibitors (ICIs) anti-PD-1 are the standard first-line therapy for patients (pts) with metastatic renal cell carcinoma (mRCC). Intestinal microbiota composition could influence ICIs activity in mRCC and other cancers, while FMT is currently used to regulate microbiota-related diseases. TACITO trial (NCT04758507) investigated whether FMT could increase the efficacy of VEGFR-TKI+ICI combinations in mRCC.

Methods

mRCC pts treated with axitinib+pembrolizumab (axi+pembro) in first-line were randomized (1:1) to FMT or placebo (pbo). Pts received direct infusion in the colon of stools from a donor or pbo at baseline (within 8 weeks from the start of axi+pembro, FMT1), followed by oral capsules with the same frozen stools or pbo at 90 (FMT2), and 180 days (FMT3), respectively. The donor was a mRCC patient (pt) who achieved complete and long-lasting response to ICIs. The primary endpoint was to increase of ≥20% the rate of pts with no disease progression at one year (1-year PFS rate) with FMT vs. pbo. Secondary endpoints were median PFS, overall survival (OS), objective response rate (ORR), and microbiota characterization.

Results

50 pts were randomized to FMT (IMDC risk: 28% favorable, 72% intermediate-poor) or pbo (32% favorable, 68% intermediate-poor). 44 pts were evaluable for the primary endpoint (24 in the FMT group and 20 in the pbo). The 1-year PFS rate was 66.7% with FMT vs. 35.0% with pbo, p=0.036. In the overall population, after a median follow-up of 28.0 mos, the mPFS was 14.2 (95%CI, 0.9–27.6) vs. 9.2 (95%CI, 3.0–15.4) mos and the mOS was not reached vs. 25.3 (95%CI, 17.1–33.6) mos with FMT and pbo, respectively. The ORR was 54% vs. 28% in the FMT arm compared to pbo; 38% vs. 44% had SD and 8% vs. 28% had PD. Safety: only 1 pt in the pbo arm reported FMT/pbo-related adverse event (grade 3 oral mucositis) and discontinued capsules assumption.

Conclusions

The preliminary results of TACITO trial show for the first time the role of FMT in increasing the activity of ICIs-based therapies in mRCC pts.

Clinical trial identification

NCT04758507.

Editorial acknowledgement

Acknowledge:

Federica Mazzuca, Professor, Medical Oncologist at Univerisity Sant'Ándrea of Rome, for the efforts in patients enrollment

Michela Roberto, MD, PhD. Medical Oncologist at Univerisity Umberto I of Rome, for the efforts in patients enrollment

Federica Recine, MD, Medical Oncologist at San Giovanni Hospital of Rome, for the efforts in patients enrollment

Hamzaj Alketa, MD, Medical Oncologist at University Hospital of Florence, for the efforts in patients enrollment

Diana Giannarelli, Statistician. Fondazione Policlinico A. Gemelli IRCCS, Rome, for the support in the statistical analysis

Legal entity responsible for the study

Fondazione Policlinico A. Gemelli, IRCCS, Rome.

Funding

Bando Ricerca Finalizzata 2018; GR-2018-12365734.

Disclosure

C. Ciccarese: Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Speaker’s Bureau: Astellas, AstraZeneca, Novartis; Financial Interests, Personal, Speaker, Consultant, Advisor: J&J, Eisai. R. Iacovelli: Financial Interests, Personal, Advisory Board: MSD, Pfizer, BMS, Eisai, Astellas; Financial Interests, Personal, Invited Speaker: Ipsen. All other authors have declared no conflicts of interest.