Table 3 Ongoing clinical trials investigating the association between gut microbiome interventions and immunotherapy
Tumor (estimated enrollment) | Intervention (intervention model) | Primary outcome | Secondary outcome | status | ClinicalTrials.gov Identifier |
|---|---|---|---|---|---|
Advanced RCC (N = 30) | Clostridium butyricum probiotic strain (CBM588) in combination with nivolumab/ipilimumab (parallel assignment) | Change in Bifidobacterium composition of stool | Change in Shannon index; ORR; PFS | Recruiting | NCT03829111 |
Solid tumor (N = 132) | Probiotic strain (MRx0518a) in combination with pembrolizumab (single group assignment) | Safety and clinical benefit of MRx0518 in combination with pembrolizumab | ORR; DoR; DCR; PFS | Recruiting | NCT03637803 |
Operable stage I-III breast cancer | Probiotics RBX7455 prior to surgery (single group assignment) | Safety | Systemic immunomodulatory effects | Recruiting | NCT04139993 |
Advanced melanoma (actual enrollment = 14) | Experimental: vancomycin pretreatment plus oral microbiome intervention (SER-401) in combination with nivolumab (parallel assignment) | Percentage of patients with AEs | ORR; DCR; PFS; OS; DoR; Change in the percentage of CD8+cells in tumor tissue | Active, not recruiting | NCT03817125 |
Surgically resectable pancreatic cancer (actual enrollment = 0) | Antibiotics in combination with pembrolizumab (single group assignment) | Change in immune activation in pancreatic tumor tissue | NA | Withdrawn (suspended due to primary investigator’s decision) | NCT03891979 |
Advanced lung adenocarcinoma (N = 30) | Oral RMT capsule in combination with durvalumab/durvalumab plus chemotherapy (single group assignment) | ORR; Safety of RMT | PFS; OS; DoR; irAEs; ORR; QoL; | Not yet recruiting | NCT04105270 |
Solid tumor (N = 65) | METb (MET-4 strains) in combination with ICIs (parallel assignment) | Cumulative relative abundance of ICI-responsiveness associated species; Changes in relative abundance of ICI-responsiveness associated MET-4 strains; Cases of treatment-related AEs | Cumulative relative abundance of ICI-responsiveness associated species at later time; Changes in relative abundance of ICI-responsiveness associated MET-4 strains at later time; Bacterial taxonomic diversity | Recruiting | NCT03686202 |
Castration-resistant metastatic prostate cancer (N = 32) | Responder-derived FMT in combination with pembrolizumab and enzalutamide (single group assignment) | Anticancer effect (Percentage of participants with a PSA decline of ≥50%) | Percent PSA change; Radiographic RR; Time to PSA progression; Time to radiographic progression; PFS; OS; Time to next therapy; Safety | Recruiting | NCT04116775 |
Anti-PD-1-resistant melanoma (N = 40) | Responder-derived FMT (single group assignment) | Incidence of FMT-related AEs; Changes in gut bacterial composition | Changes in composition and activity of immune cells | Recruiting | NCT03353402 |
Anti-PD-1-resistant advanced melanoma (N = 20) | Responder-derived FMT in combination with pembrolizumab (single group assignment) | ORR | Change in T-cells composition, innate/adaptive immune system subsets and function of T-cells | Recruiting | NCT03341143 |
Advanced melanoma or NSCLC (N = 50) | Responder-derived FMT in combination with nivolumab (single group assignment) | Incidence of FMT-related AEs; ORR | Changes in immune activation in the gut and tumor; PFS; OS; DoR; Anti-PD-1-related immune toxicities | Not yet recruiting | NCT04521075 |
Advanced melanoma (N = 20) | A healthy donor-derived FMT in combination with pembrolizumab/nivolumab (single group assignment) | Safety of combining FMT and immunotherapy | ORR; changes in gut microbiome, immune blood biomarkers and metabolomics | Recruiting | NCT03772899 |
Anti-PD-1-resistant gastrointestinal cancers (N = 10) | FMT in combination with anti-PD-1 (single group assignment; healthy people who have the gut microbiota profile similar to the responders of anti-PD-1 will be identified as donor) | ORR; AEs; Rate of abnormal vital signs and laboratory test results | Change in T-cells composition, subsets of immune system; Function of T-cells; Association of anti-PD-1 response with gut microbiota; AEs; Rate of abnormal vital signs, PE and ECG and laboratory test results | Recruiting | NCT04130763 |
Metastatic colorectal adenocarcinoma (N = 15) | Responder-derived FMT in combination with pembrolizumab /nivolumab (single group assignment) | ORR | NA | Not yet recruiting | NCT04729322 |
RCC (N = 20) | Healthy donors-derived FMT in combination with nivolumab and ipilimumab (single group assignment) | Occurrence of immune-related colitis | Incidence of irAEs; ORR; Change in microbiome and immune response; QoL | Recruiting | NCT04163289 |
Postoperative stage II/III CRC (N = 294) | Oral metronidazole before postoperative chemotherapy (parallel assignment) | DFS | OS; RR | Recruiting | NCT04264676 |