Table 1.
Combination studies with 223Ra in patients with mCRPC.
| Clinical trial registration number | Intervention | Phase | Primary outcome | Results |
|---|---|---|---|---|
| Chemotherapy | ||||
| NCT03737370 | Radium-223 55 kBq/kg Q4W + Docetaxel Q2W (escalating doses) | I | Incidence of DLTs | NA, recruitment ongoing |
| NCT03574571 | Radium-223 55 kBq/kg Q6W + Docetaxel 60 mg/m2 Q3W X 10 vs. Docetaxel 75 mg/m2 Q3W alone | III | OS | NA, recruitment ongoing |
| NCT01106352 | Radium-223 50 kBq/kg Q6W + Docetaxel 60 mg/m2 Q3W X 10 vs. Docetaxel 75 mg/m2 Q3W alone | I/II | Incidence of DLTs and AEs | The RP2D for the combination was radium-223 55 kBq/kg Q6W × 5 doses, + docetaxel 60 mg/m2 Q3W × 10 doses. Median time to PSA progression favored the combination (6.6 vs. 4.8 m) |
| Immunotherapy | ||||
| NCT03093428 | Radium-223 55 kBq/kg Q4W + Pembrolizumab 200 mg Q3W vs. Radium-223 55 kBq/kg Q4W alone | II | Number of Participants with Increased Immune Cell Infiltration Across Arms | No difference between Arm A and B in rPFS (6.7 m vs. 5.7 m) or OS (16.9 vs. 16.0 m) No evidence of increased CD4+ or CD8+ T-cell infiltration in Arm A |
| NCT04109729 | Radium-223 55 kBq/kg Q4W + Nivolumab 480 mg Q4W | I/II | Safety, ctDNA reduction after 6 weeks of nivolumab treatment | NA, recruitment ongoing |
| NCT02814669 | Radium-223 55 kBq/kg Q4W + Atezolizumab 480 mg Q2W | I | Incidence of DLTs and AEs, ORR | ORR 6.3%, Median rPFS 3.0 m, Median OS 16.3 m No clear evidence of benefit with increased toxicity in combination than either drug alone |
| NCT04071236 | Radium-223 Q4W x 6 + Peposertib +/- Avelumab Q2W vs. Radium-223 Q4W x 6 alone | I/II | Incidence of DLTs, rPFS | NA, recruitment ongoing |
| NCT02463799 | Radium-223 50 kBq/kg Q4W + Sipuleucel-T Q2W vs. Sipuleucel-T Q2W alone | II | Immune responses to treatment with Sipuleucel-T measured by peripheral PA2024 T-cell proliferation | Higher 50% PSA response rate (31 vs. 0%) and longer PFS (39 vs. 12 w) and OS (NR vs. 2.6 y) seen in combination arm |
| Anti-androgen therapy | ||||
| NCT02199197 | Radium-223 55 kBq/kg Q4W + Enzalutamide 160 mg daily vs. Enzalutamide alone | II | Incidence of AEs, change in serum N-telopeptides from baseline | No statistically significant difference in OS, rPFS, PSA PFS PSA PFS2 improved with combination (18.7 vs. 8.4 m) |
| NCT02194842 | Radium-223 55 kBq/kg Q4W + Enzalutamide 160 mg daily vs. Enzalutamide alone | III | rPFS | NA, recruitment ongoing |
| NCT02043678 (ERA-223) | Radium-223 55 kBq/kg Q4W + Abiraterone Acetate 1000 mg daily and Prednisolone vs. Abiraterone alone | III | Symptomatic skeletal event free survival | No improvement in OS or median symptomatic skeletal event-free survival |
| PARP inhibitors | ||||
| NCT03317392 | Radium-223 Q4W + Olaparib | I/II | MTD of Radium-223 and Olaparib, rPFS | NA, recruitment ongoing |
| NCT03076203 | Radium-223 Q4W + Niraparib | I | MTD | The MTD of Niraparib was 100 mg in the chemo-exposed arm and 200 mg in the chemo-naïve arm |