Science | first human trial Phase II clinical conclusion...

Recently, researchers at upMC Hillman Cancer Center and the U.S. National Cancer Institute demonstrated that changing the gut microbiome can turn patients with advanced melanoma who do not respond to immunotherapy into responders.
February 5, Science published the results of this principle-validated Phase II one-arm clinical trial (NCT03341143).
is also the first study to test this view in humans.
in that study, researchers at upMC Hillman Cancer Center performed a combined anti-PD-1 immunotherapy (FMT) combined with anti-PD-1 immunotherapy for patients who received all available treatments, including anti-PD-1, and then tracked clinical and immune outcomes.
at the U.S. National Cancer Institute analyzed samples of the patients' microbiomes to see why FMT appeared to enhance their response to immunotherapy.
specifically, the study recruited 16 melanoma patients between June 2018 and January 2020, and the results now analyze data up to September 1, 2020.
all melanoma patients who had previously been treated against PD-1 monodratives or combined anti-CTLA-4 or other research drugs did not respond and were assessed by RECISTv1.1 as patients with primary progressive disease.
All recruited patients and candidates (4 out of 7 patients in complete remission and 3 partial remission, with a medium progression-free lifetime of 56 months) were subjected to continuous fecal sampling and extensive infectious disease studies to eliminate the possibility of infectious diseases.
Then, fMT from a single source is administration with the anti-PD-1 drug Pabliju monoantigen (below), and then Paboliju monoantitherapy is performed every 3 weeks until the disease progresses or becomes intolerable toxicity.
is that this attempt has worked, " he said.
3 out of 15 patients (PT-18-0032, complete remission; PT-18-0007 and PT-19-0024, partially relieved) had objective responses (objective response rate) 20%); 3 cases (PT-18-0018, PT-19-0002 and PT-19-0010) showed stable ongoing disease for 12 months (figure below).
follow-up for 7 months, with a medium progress-free lifetime (PFS) and total survival (OS) of 3 and 7 months for all patients, respectively.
in 6 patients with disease control (i.e., objective response and disease stabilization), the median PFS and OS were 14 and 14 months, respectively (Figure B above).
noteworthy that one of these patients (PT-18-0007) showed sustained partial remission over a two-year period and is currently being monitored.
, co-author of the study, said: "Patients treated in this trial were very unlikely to respond spontaneously to the second anti-PD-1 immunotherapy.
, any positive reaction should be attributed to FMT.
" In addition, in this study, sample analysis of FMT recipients revealed immune changes in the blood and tumor sites, indicating an increase in immune cell activity in the respondent rather than an increase in immunosuppression in the respondent.
artificial intelligence (transkingdom network analysis) confirms that the gut microbiome regulates these changes.
transkingdom network analysis.
CXCL8 (IL-8), IL-10 and CCL3 (MIP-1a) and the microorganisms (Bacteroides uniformis, Bacteroids) in pre-treatment non-responders es Nordii, Phascolarctobacterium faecium, etc.) were positively related to the microorganisms rich in the body of the post-treatment responders (e.g., Ruminococcus flavefaciens and F. prausnitzii).
(source: Science) safety, treatment-related adverse events (AEs) are rare (see table below).
AE occurred at least once in all patients, most were low (level 1, 72.9%; level 2, 20.0%).
. Divakar Davar, co-lead author of the
FMT/Paboliju single anti-treatment clinical trial adverse event summary (n-16) article, said: "FMT is only a means to an end.
we know the composition of the gut microbiome - gut bacteria have the potential to change a patient's response to immunotherapy.
but gut bacteria are about 100 trillion, which are the 'good' bacteria? "FMT provides a way to capture a large number of candidate microorganisms, testing trillions at a time to see if carrying "good" bacteria can make more people sensitive to PD-1 inhibitors.
Davar and Zaour hope to conduct larger trials in melanoma patients and assess whether FMT is effective in treating other cancers.
, they aim to replace FMT with tablets containing the most beneficial microbial mixtures to promote immunotherapy, but it will still take years.
, Zarour said: "While much remains to be done, our research is ultimately promising for microbiome-based cancer treatment.
" References: 1 s Fecal catethings cancer cancer immunotherapy non-responders into responders (Source: Medical press) 2 s Diwakar Davar et al. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science (2021). DOI:10.1126/science.abf3363