Universal donor.

Top Line: The gut microbiome is coming back into the spotlight with the first human interventional trial.

The Study: Early adopters of QuadShot may remember the hype around the hypothesis that a “healthy” microbiome can actually drive better tumor responses to anti-PD-1 therapy for melanoma. It’s 4 years later, and we have a phase 1 trial evaluating this concept in 10 patients with metastatic melanoma refractory to anti-PD-1 therapy. How did they induce a change in gut microbiome you ask? A novel targeted therapy with an undisclosed price tag..? Nope, with a good ol’ fecal transplant, with the preliminary heavy lifting done by mice. The donor feces came from two patients with metastatic melanoma who achieved complete responses, durable for at least one year, to anti-PD-1 therapy. Enrollees all progressed on at least one anti-PD-1 therapy, as well as at least one BRAF-inhibitor in the setting of a BRAF-V600E mutation. They began with a depletion of their native gut microbiome via vancomycin + neomycin then a fecal transplant via colonoscopy followed by oral “stool capsules” with standard-dose nivolumab infusion every 14 days for 90 days total. Note: patients were instructed not to chew or crush capsules, for the love of God. There are lots of basic science goodies included in the manuscript, but the clinical takeaway is a response rate of 3/10, including one complete responder. Can we make much from a series of 10 patients? Of course not, especially considering this response rate can be seen with reintroducing immune checkpoint inhibition alone. But the microbiome plays an increasingly important role in immunotherapy response, and its modulation via fecal transplant or otherwise may be an exciting new way to enhance response. 

TBL: Modulating the microbiome via fecal transplant may prove an effective adjuvant to immune checkpoint inhibition. | Baruch, Science 2021