Table 1.

Published and ongoing therapeutic and observational microbiome intervention trials

NCT	Trial phase/type	Patient selection	Treatment	N	CBR	ORR	Status	Ref
Procedural FMT
NCT03341143	Pilot/phase 1	PD-1 refractory	Pembrolizumab + FMT via colonoscopy1	16	6/15	3/15	Results published	[153]
NCT03353402	Phase 1	PD-1 refractory	Nivolumab + oral FMT2	10	3/9	3/9	Results published	[154]
NCT04577729	Randomized	ICI refractory metastatic melanoma	Checkpoint inhibitor + FMT4 versus sham FMT	60*	NR	NR	Recruiting, Medical University Graz
NCT03819296	Phase 1/2	Checkpoint inhibitor with GI complications in melanoma, lung, and GU	Endoscopic FMT	800	NR	NR	Recruiting, MD Anderson Cancer Center (Houston, TX)
NCT04988841 (PICASSO)	Phase 2, randomized	Checkpoint naïve unresectable or metastatic melanoma	Checkpoint inhibitor + MaaT013a enema versus placebo	60*	NR	NR	Not yet recruiting, Hôpitaux de Paris
NCT05251389	Phase 1	Checkpoint refractory melanoma	Endoscopic placed FMT	24	NR	NR	not yet recruiting, The Netherlands Cancer Institute
NCT05273255	Pilot	Checkpoint refractory melanoma	Endoscopic placed FMT	30	NR	NR	Recruiting, University of Zurich
Oral FMT/microbial supplement
NCT04951583 (FMT-LUMINATE)	Phase 2, single group	Untreated NSCLC and melanoma	Nivolumab + Ipilimumab + FMT capsules	70*	NR	NR	Not yet Recruiting, CHUM
NCT03772899 (MIMic)	Phase 1	Unresectable or metastatic melanoma	FMT3 capsule + checkpoint	20*	NR	NR	Active, not recruiting, multiple Canadian sites
NCT04521075	Phase 1b	Stage IV NSCLC and unresectable and metastatic melanoma	Nivolumab + FMT4 oral capsules	42*	NR	NR	Recruiting, Sheba medical center
NCT03934827 (MICROBIOME)	Phase 1	Resectable select solid tumors (including melanoma)	MRx0518b capsules versus placebo BID 2–4 weeks prior to surgery	120*	NR	NR	Recruiting, Imperial College London
NCT03817125	Phase 1b	Unresectable or metastatic melanoma	Nivolumab + SER-401c versus placebo	10	NR	NR	Active not recruiting, multiple US sites	[163, 164]
Behavioral diet intervention
NCT04866810 (EDEN)	Randomized behavioral intervention	Untreated unresectable or metastatic Melanoma	Anti-PD1/PDl1 + observation vs. behavioral diet	60*	NR	NR	Recruiting, National Cancer Institute (Bethesda, MD)
NCT04645680 (DIET)	Phase 2, randomized	Stage 3 or 4 melanoma	Standard of care immunotherapy with dietary intervention (isocaloric high fiber vs. isocaloric whole foods diet)	42	NYR	NYR	Recruiting, MD Anderson (Houston, Texas USA)
Observational trials
NCT	Patient Selection	Treatment	Test/observation	Primary Outcome	N	Status
NCT04107168 (MITRE)	Stage 3 or 4 melanoma, advanced renal cell carcinoma, advanced NSCLC	Anti-PD-1 or anti-PD-1 with anti-CTLA4	Saliva and stool samples		1800 (up to 360 healthy controls)	Recruiting, multiple sites in UK
NCT03643289 (PRIMM)	Stage 3 or 4 melanoma naïve to immunotherapy	Standard of care immunotherapy	Gut microbiome with metagenomics of stool samples with diet survey		450	Recruiting, multiple sites in UK
NCT04734704 (SKINBIOTA)	Melanoma on immunotherapy and non-melanoma vitiligo	Anti-PD-1 as standard of care	Skin swabs on lesional and non-lesional sites		175	Not yet recruiting, Hopital Saint-Andre (Bordeaux, France)
NCT05037825 (PARADIGM)	NSCLC, Malignant melanoma, RCC, TNBC	Anti-PD-1, anti-PD-L1, anti-CTLA-4 as single agents or in combinations	Longitudinal stool specimens		800	Recruiting, Baptist Health Clinical Research (Elizabethtown, Kentucky, USA)
NCT03643289 (PRIMM)	Stage 3 and 4 melanoma	Checkpoint inhibitors	Stool sample		450	Recruiting, Multiple Institution, UK
NCT05102773	Stages 3 and 4 melanoma	Checkpoint inhibitors	Stool and blood samples	Alpha-diversity change	89	Recruiting, Single Institution, Ohio State University, (Columbus, Ohio)
NCT04875728	Stage I–II melanoma	Surgery + cefazolin surgical prophylaxis	Stool sample	Change of microbiome after prophylactic antibiotics	20	Recruiting, MD Anderson (Houston, Texas USA)
NCT04136470	Melanoma and NSCLC	Checkpoint inhibitors	Stool sample	Microbial diversity as assessed in gut microbiome	130	Recruiting, Multiple sites (Poland)
NCT04698161 (BIOMIS-Onco)	Melanoma and NSCLC	Checkpoint inhibitors	Stool, blood, saliva, and urine	Microbe biobank collection	50	IRCCS Istituto Tumori Giovanni Paolo II (Bari, Italy)
NCT02600143 (COLIPI)	Melanoma with colitis	Checkpoint inhibitors	Stool samples	Longitubindal Gut microbiome differences in colitis development	123	UMCG (Groningen, Netherlands)

^*Planned enrollment, **status per clinicaltrials.gov. ^AMaaT013 is a microbiome restoration biotherapeutic composed of pooled-donor, full ecosystem intestinal microbiome of approximately 455 species. ^BMRx0518 is lyophilized formulation of a proprietary strain of enterococcus species of bacterium. ^CSER-401 a purified suspension of firmicute spores from healthy human donors formulated into capsules. CBR clinical benefit rate, CHUM Centre hospitalier de l'Université de Montréal, FMT fecal microbiota transplant, GU genitourinary, NR not reported, NSCLC non-small cell lung cancer, ORR objective response rate, UPMC University of Pittsburgh Medical Center. ¹FMT derived from healthy donors who achieved complete response or partial response with PD-1 therapy. ²FMT derived from 2 healthy donors who achieved complete response or partial response with PD-1 for > 1 year. ³FMT derived from 2 healthy donors per institutional guidelines. ⁴FMT will be given from 1 of 5 donors. Donors will be patients with metastatic melanoma achieving remission for ≥ 1 year