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. 2022 Jun 24;28(20):4370–4384. doi: 10.1158/1078-0432.CCR-21-1129

Table 2.

List of clinical trials evaluating microbiome therapeutics in cancer.

Sponsor and trial information Nature of product Clinical trial information Dose Antibiotic conditioning Enrollment status ORR/DCR TRAE
FMT
Baruch et al. (142) Donor (melanoma PD-1 responder) PD-1 primary and secondary refractory melanoma Colonoscopic FMT (day 0), then oral FMT capsules (day 1 and day 12), repeated every 2 weeks along with nivolumab. Nivolumab 240 mg every 2 weeks. Yes Not active 30% No moderate-to-severe irAEs
Davar et al. (51) Donor (melanoma PD-1 responder) PD-1 secondary refractory melanoma Single responder-derived FMT (day 1). Pembrolizumab 200 mg every 3 weeks. No Not active 20%/40% 3 grade 3 irAEs (2 instances fatigue, 1 peripheral motor neuropathy)
NCT04729322 Donor (dMMR–PD-1 responder) dMMR patients following progression on PD-1 Cycle 1: FMT induction via colonoscopy (day 5), then capsules on days 1, 8, 15. Cycles 2+: FMT capsules on day 1 every 3 weeks. Metronidazole, vancomycin, neomycin Active, enrolling Not reported Not reported
NCT04130763 Healthy donors with microbiome profiles similar to PD-1 responders GI cancers following progression on PD-1 Cycle 1: FMT capsules for 1 week as induction. Cycles 2: FMT capsule maintenance. None Active, enrolling Not reported Not reported
MiMic (NCT03772899) Healthy donor PD-1 naïve metastatic melanoma in combination with nivolumab FMT induction preimmunotherapy. FMT maintenance with nivolumab or pembrolizumab. None Active, enrolling Not reported Not reported
Complete consortia products
MCGRAW (NCT03817125, Seres) Orally bioavailable encapsulated consortia of commensal bacteria

  • PD-1 naïve metastatic melanoma in combination with nivolumab vs. placebo PD-1 refractory melanoma in combination with nivolumab

 SER-401 capsule once daily for 7 days (lead-in), then daily. Nivolumab per label. Vancomycin, 5 days Active, not enrolling Not reported Not reported
PICASSO (NCT03772899, MaaT Pharma) Healthy donor–derived full-spectrum microbiome therapeutic (MaaT033)

  • PD-1 naïve metastatic melanoma

 MaaT033 every 3 weeks (weeks 0–9), then every 12 weeks (weeks 15–23); total 7 infusions. None Active, enrolling Not reported Not reported
Synthetic bacterial consortia
VE800 (Vedanta) Orally bioavailable LBP containing 11 distinct nonpathogenic, nontoxigenic, commensal bacterial strains Select histologies following failure of standard therapy in combination with pembrolizumab (NCT04208958):

  • Melanoma

  • MSS CRC

  • Gastric and GE cancer

 VE800 5 capsules loading, then 2 capsules daily. Nivolumab per label. Vancomycin, 5 days Active, not enrolling Not reported Not reported
Monoclonal microbial candidates
Miyarisan Pharmaceutical Orally bioavailable bifidogenic Clostridium butyricum strain MIYAIRI588 (CBM588) Advanced RCC in combination with nivolumab and ipilimumab (NCT03829111) (143) CBM588 890 mg twice daily. None Completed 58% (nivo/ipi + CBM588) vs. 20% (nivo/ipi) Grade 3/4 AEs: 52% (nivo/ipi + CBM588) vs. 50% (nivo/ipi)
Advanced RCC in combination with nivolumab and cabozantinib (NCT05122546) None Active, enrolling Not reported Not reported
Evelo Orally bioavailable monoclonal microbial derived from single clone of Bifidobacterium spp. PD-1 refractory melanoma in combination with pembrolizumab (NCT03595683) EDP1503 capsules twice daily for 14 days (lead-in), then twice daily; each capsule contains ≥ 7.5 x 1010CFUs. Pembrolizumab per label. None Suspended Not reported Not reported
Multiple histologies following failure of standard therapy in combination with pembrolizumab (NCT03775850):

  • Cohort A: MSS CRC

  • Cohort B: TNBC

  • Cohort C: NSCLC, bladder cancer; GE cancer, any microsatellite unstable, or RCC

 None Active, not enrolling Not reported Not reported
NCT03637803 (4d Pharma) Orally bioavailable LBP containing Enterococcus gallinarum flagellin, which has TLR5 stimulatory properties Select histologies following failure of standard therapy in combination with pembrolizumab (NCT03775850):

  • RCC

  • NSCLC

 MRx0518 capsules twice daily. Pembrolizumab per label. None Active, not enrolling Not reported Not reported
Oncomimics
ROSALIE, NCT04116658 (Enterome) EO2401: multipeptide (3) vaccine containing peptides (oncomimic), which are strongly homologous but not identical to key tumor antigens in select tumors Glioblastoma following failure of standard therapy in 3 cohorts:

  • Cohort 1: EO2041 monotherapy, followed by sequential EO2041 and nivolumab

  • Cohort 2: Concurrent EO2041 and nivolumab

  • Cohort 3: EO2041 and nivolumab and bevacizumab

 EO2401 multiple doses. Nivolumab and bevacizumab per label. None Active, not enrolling Not reported Not reported
Prebiotics, postbiotics, probiotics, and dietary interventions
NCT05220124 (Tianjin Medical University Second Hospital, Tianjin, China) Live combined (Bifidobacterium spp., Lactobacillus spp., and Enterococcus spp.) probiotic capsules Prospective phase IV randomized trial of immunotherapy ± live combined probiotic capsules in platinum-ineligible metastatic urothelial cancer Live combined probiotic capsules 420 mg twice daily for 3–4 cycles. None Active, enrolling Not reported Not reported
NCT04699721 (Xiangya Hospital of Central South University, Hunan, China) Unnamed probiotic Phase I trial of nivolumab with carboplatin and paclitaxel and probiotic in resectable NSCLC Not stated None Active, enrolling Not reported Not reported
EDEN, NCT04866810 (NIH) Dietary and exercise intervention Randomized phase II study of anti–PD-L1 immunotherapy ± dietary and exercise intervention in cancer patients Plant-based, high-fiber diet and exercise (150 minutes moderate-intensity, 75 minutes high-intensity weekly) None Active, enrolling Not reported Not reported
DIET (NCT04645680) Isocaloric high-fiber diet Randomized, double-blind phase II study evaluating high-fiber diet in patients with resectable stage III/IV melanoma following definitive surgery Isocaloric high-fiber diet (Arm 1) vs. isocaloric control diet (Arm 2) None Active, enrolling Not reported Not reported
NCT03700437 Intermittent fasting diet Nonrandomized pilot phase II study of intermittent fasting diet in patients with stage III NSCLC following definitive chemoimmunotherapy (CIT) Chemolieve®, a plant-based FMD that provides ∼300 calories/fasting day None Active, enrolling Not reported Not reported
CETOREIN (NCT04316520) Ketogenic diet Nonrandomized pilot phase II study of ketogenic diet in patients with advanced RCC receiving immunotherapy Ketogenic diet None Active, enrolling Not reported Not reported

Abbreviations: CFU, colony-forming units; dMMR, deficient mismatch repair; FMD, fasting mimicking diet; GE, gastroesophageal; LBP, live bacterial product; NHL, non-Hodgkins lymphoma; nivo/ipi, nivolumab/ipilimumab; NSCLC, non–small cell lung cancer; MSS CRC, microsatellite stable colorectal carcinoma; TNBC, triple-negative breast cancer; RCC, renal cell carcinoma.