Table 4.
Novel Combinations of Immunotherapy Under Investigation in R/R PTCLs
| Agent(s) | ClinicalTrials.gov | Phase | N | Treatment | Primary Endpoint(s) |
|---|---|---|---|---|---|
| Pembrolizumab + romidepsin | NCT03278782 | I/II | 39 | Romidepsin IV on days 1 and 8 and pembrolizumab IV on day 1. Cycles repeat every 21 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity. | DLT (phase I) ORR (phase II) |
| Pembrolizumab + pralatrexate | NCT03598998 | I/II | 40 | Pralatrexate IV on days 1 and 8, pembrolizumab IV on day 1. Courses repeat every 21 days for up to 24 months in the absence of disease progression or unacceptable toxicity. | MTD (phase I) ORR (phase II) |
| Durvalumab ± lenalidomide | NCT03011814 | I/II | 62 | Arm I: durvalumab IV on day 1 repeated every 28 (± 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity. Arm II: durvalumab IV on day 1 and lenalidomide PO QD on days 1–21. Treatment repeated every 28 (± 3) days for up to 13 courses in the absence of disease progression or unacceptable toxicity. |
CTCL specific response assessed by Lugano Classification Dose limiting toxicity assessed by CTCAE version 4.03 Duration of complete response EFS Incidence of AEs ORR OS PFS DOR Time to response |
| Durvalumab + pralatrexate, romidepsin and oral 5-Azacitidine | NCT03161223 | I/II | 148 | Arm A: 7-day lead-in phase of 5-azacitidine. 5-azacitidine PO from day 1 to day 14, durvalumab IV on day 8 and romidepsin IV on days 8 and 15 of a 28-day treatment cycle Arm B: Durvalumab IV on day 1, pralatrexate IV on days 1 and 15, and romidepsin IV on days 1 and 15 on a 28-day cycle Arm C: Durvalumab IV on day 1 and romidepsin IV on days 1, 8, and 15 of a 28-day cycle Arm D: 7-day lead-in phase of 5-azacitidine. 5-azacitidine PO from day 1 to day 14 and durvalumab IV on day 8 of a 28-day cycle |
MTD |
| Pembrolizumab + decitabine + pralatrexate | NCT03240211 | Ib | 42 | Arm A: pembrolizumab 200 mg IV day 1 with pralatrexate 30 mg/m2 IV day 1, 8, and 15 Arm B: pembrolizumab 200 mg IV day 8 with pralatrexate 20 mg/m2 IV day 1, 8, and 15 and decitabine 10 mg/m2 from day 1 to 5 Arm C: pembrolizumab 200 mg IV and decitabine 20 mg/m2 from day 1 to 5 |
Estimated MTD Recommended phase II dose |
Abbreviations: DLT, dose limiting toxicity; ORR, objective response rate; MTD, maximum tolerated dose; EFS, event-free survival; CR, complete response; DOR, duration of response; PFS, progression-free survival; OS, overall survival; AE, adverse events; IV, intravenously; PO, per os.