Summary of selected trials investigating novel agents for relapsed/refractory PTCL
| Agent(s) . | Study phase . | Trial . | Patient population . | # evaluable patients . | Efficacy: overall . | Efficacy: subgroups . |
|---|---|---|---|---|---|---|
| Single agents | ||||||
| Romidepsin20,21 | 2 | NCT00426764 | R/R PTCL | 130 | ORR 25% CR/CRu 15% mDOR 17 mo mPFS 4 mo | AITL (n = 27): ORR 30%, CR/CRu 19% PTCL-NOS (n = 69): ORR 29%, CR/CRu 14% ALK- ALCL (n = 21): ORR 24%, CR 19% |
| Belinostat23 | 2 | BELIEF (CLN-19) | R/R PTCL | 129 | ORR 26% CR 11% mDOR 13.6 mo mPFS 1.6 mo, mOS 7.9 mo | AITL (n = 10): ORR 45% PTCL-NOS (n = 18): ORR 23% ALK- ALCL (n = 13): ORR 15% |
| Azacitidine*25 | 3 | ORACLE (NCT03593018) | R/R AITL or nodal TFH lymphoma | 86 | 3-mo ORR 33% 3-mo CR 12% mPFS 5.6 mo mOS 18.4 mo | N/A |
| Valemetostat*30 | 2 | VALENTINE-PTCL01 (NCT04703192) | R/R PTCL (including ALCL with prior BV exposure) | 133 | ORR 44% CR 14% mDOR 11.9 mo mPFS 5.5 mo mOS 17.0 mo | AITL (n = 42): ORR 55%, CR 19% PTCL-NOS (n = 41): ORR 32%, CR 10% PTCL-TFH (n = 8): ORR 50%, CR 12% |
| Brentuximab vedotin17 | 2 | NCT01421667 | R/R CD30+ PTCL excluding ALCL | 34 | ORR 41% CR 24% mDOR 7.6 mo mPFS 2.6 mo | AITL (n = 13): ORR 54%, CR 38% PTCL-NOS (n = 21): ORR 33%, CR 14% |
| Crizotinib18 | 2 | NCT02419287 | R/R ALK+ ALCL | 12 | ORR 83% CR 58% mDOT 16.5 mo mPFS NR mOS NR | N/A |
| Duvelisib*26 | 2 | PRIMO (NCT03372057) | R/R PTCL | 101 | ORR 49% CR 34% mPFS 3.6 mo | AITL (n = 30): ORR 67%, CR 53% PTCL-NOS (n = 52): ORR 48%, CR 27% ALCL (n = 15): ORR 13%, CR 13% |
| Pralatrexate12 | 2 | PROPEL (NCT00364923) | R/R PTCL | 109 | ORR 29% CR/CRu 18% mDOR 10.1 mo mPFS 3.5 mo mOS 14.5 mo | AITL (n = 13): ORR 8% PTCL-NOS (n = 59): ORR 32% ALCL (n = 17): ORR 35% |
| Golidocitinib*29 | 2 | JACKPOT8 (NCT04105010) | R/R PTCL | 88 | ORR 44% CR 24% mDOR 20.7 mo mPFS 5.6 mo mOS 19.4 mo | AITL (n = 16): ORR 56% PTCL-NOS (n = 46): ORR 46% ALCL (n = 10): ORR 10% |
| Combination therapies | ||||||
| Romidepsin + pralatrexate*37 | 1 | NCT01947140 | R/R lymphoma | 23 | ORR 57% CR 17% mPFS 3.7 mo mOS 13.8 mo | TCL (n = 14): ORR 71% mDOR 4.29 mo mPFS 4.4 mo mOS 12.4 mo |
| Romidepsin + duvelisib*38 | 1b/2 | NCT02783625 | R/R PTCL | 48 | ORR 56% CR 44% mDOR 12 mo mOS 12 mo | AITL (n = 12): ORR 71% PTCL-NOS (n = 8): ORR 47% ALCL (n = 3): ORR 100% |
| Romidepsin + azacitidine*39 | 2 | NCT01998035 | Treatment-naïve or R/R PTCL | 23 | ORR 61% CR 48% mDOR 20.3 mo mPFS 8 mo mOS NR | R/R PTCL (n = 13): ORR 70%, CR 50% mDOR 13.5 mo mPFS 8 mo mOS 20.6 mo TFH (n = 15) ORR 80%, CR 60% mPFS 8.9 mo mOS NR |
| Romidepsin + lenalidomide*40 | 1b/2 | NCT01755975 | R/R NHL or HL | 45 | ORR 49% CR 18% mDOR 15.7 mo mPFS 5.7 mo mOS 24 mo | R/R PTCL (n = 15) ORR 53% CR 13% PTCL-NOS (n = 5) ORR 40% ATLL (n = 6): ORR 50% AITL (n = 2): ORR 100% |
| Romidepsin + lenalidomide + carfilzomib*40 | 1b/2 | NCT02341014 | R/R NHL or HL | 27 | ORR 48% CR 20% mDOR 10.6 mo mPFS 3.4 mo mOS 26.5 mo | R/R PTCL (n = 13) ORR 54% CR 39% PTCL-NOS (n = 7): ORR 29% AITL (n = 5): ORR 100% |
| Agent(s) . | Study phase . | Trial . | Patient population . | # evaluable patients . | Efficacy: overall . | Efficacy: subgroups . |
|---|---|---|---|---|---|---|
| Single agents | ||||||
| Romidepsin20,21 | 2 | NCT00426764 | R/R PTCL | 130 | ORR 25% CR/CRu 15% mDOR 17 mo mPFS 4 mo | AITL (n = 27): ORR 30%, CR/CRu 19% PTCL-NOS (n = 69): ORR 29%, CR/CRu 14% ALK- ALCL (n = 21): ORR 24%, CR 19% |
| Belinostat23 | 2 | BELIEF (CLN-19) | R/R PTCL | 129 | ORR 26% CR 11% mDOR 13.6 mo mPFS 1.6 mo, mOS 7.9 mo | AITL (n = 10): ORR 45% PTCL-NOS (n = 18): ORR 23% ALK- ALCL (n = 13): ORR 15% |
| Azacitidine*25 | 3 | ORACLE (NCT03593018) | R/R AITL or nodal TFH lymphoma | 86 | 3-mo ORR 33% 3-mo CR 12% mPFS 5.6 mo mOS 18.4 mo | N/A |
| Valemetostat*30 | 2 | VALENTINE-PTCL01 (NCT04703192) | R/R PTCL (including ALCL with prior BV exposure) | 133 | ORR 44% CR 14% mDOR 11.9 mo mPFS 5.5 mo mOS 17.0 mo | AITL (n = 42): ORR 55%, CR 19% PTCL-NOS (n = 41): ORR 32%, CR 10% PTCL-TFH (n = 8): ORR 50%, CR 12% |
| Brentuximab vedotin17 | 2 | NCT01421667 | R/R CD30+ PTCL excluding ALCL | 34 | ORR 41% CR 24% mDOR 7.6 mo mPFS 2.6 mo | AITL (n = 13): ORR 54%, CR 38% PTCL-NOS (n = 21): ORR 33%, CR 14% |
| Crizotinib18 | 2 | NCT02419287 | R/R ALK+ ALCL | 12 | ORR 83% CR 58% mDOT 16.5 mo mPFS NR mOS NR | N/A |
| Duvelisib*26 | 2 | PRIMO (NCT03372057) | R/R PTCL | 101 | ORR 49% CR 34% mPFS 3.6 mo | AITL (n = 30): ORR 67%, CR 53% PTCL-NOS (n = 52): ORR 48%, CR 27% ALCL (n = 15): ORR 13%, CR 13% |
| Pralatrexate12 | 2 | PROPEL (NCT00364923) | R/R PTCL | 109 | ORR 29% CR/CRu 18% mDOR 10.1 mo mPFS 3.5 mo mOS 14.5 mo | AITL (n = 13): ORR 8% PTCL-NOS (n = 59): ORR 32% ALCL (n = 17): ORR 35% |
| Golidocitinib*29 | 2 | JACKPOT8 (NCT04105010) | R/R PTCL | 88 | ORR 44% CR 24% mDOR 20.7 mo mPFS 5.6 mo mOS 19.4 mo | AITL (n = 16): ORR 56% PTCL-NOS (n = 46): ORR 46% ALCL (n = 10): ORR 10% |
| Combination therapies | ||||||
| Romidepsin + pralatrexate*37 | 1 | NCT01947140 | R/R lymphoma | 23 | ORR 57% CR 17% mPFS 3.7 mo mOS 13.8 mo | TCL (n = 14): ORR 71% mDOR 4.29 mo mPFS 4.4 mo mOS 12.4 mo |
| Romidepsin + duvelisib*38 | 1b/2 | NCT02783625 | R/R PTCL | 48 | ORR 56% CR 44% mDOR 12 mo mOS 12 mo | AITL (n = 12): ORR 71% PTCL-NOS (n = 8): ORR 47% ALCL (n = 3): ORR 100% |
| Romidepsin + azacitidine*39 | 2 | NCT01998035 | Treatment-naïve or R/R PTCL | 23 | ORR 61% CR 48% mDOR 20.3 mo mPFS 8 mo mOS NR | R/R PTCL (n = 13): ORR 70%, CR 50% mDOR 13.5 mo mPFS 8 mo mOS 20.6 mo TFH (n = 15) ORR 80%, CR 60% mPFS 8.9 mo mOS NR |
| Romidepsin + lenalidomide*40 | 1b/2 | NCT01755975 | R/R NHL or HL | 45 | ORR 49% CR 18% mDOR 15.7 mo mPFS 5.7 mo mOS 24 mo | R/R PTCL (n = 15) ORR 53% CR 13% PTCL-NOS (n = 5) ORR 40% ATLL (n = 6): ORR 50% AITL (n = 2): ORR 100% |
| Romidepsin + lenalidomide + carfilzomib*40 | 1b/2 | NCT02341014 | R/R NHL or HL | 27 | ORR 48% CR 20% mDOR 10.6 mo mPFS 3.4 mo mOS 26.5 mo | R/R PTCL (n = 13) ORR 54% CR 39% PTCL-NOS (n = 7): ORR 29% AITL (n = 5): ORR 100% |
Not currently approved by the Food and Drug Administration for treatment of PTCL.
CRu, complete response unconfirmed; HL, Hodgkin lymphoma; mo, months; mOS, median OS; mPFS, median PFS; N/A, not available; NHL, non-Hodgkin lymphoma; R/R, relapsed/refractory.
Note: No head-to-head studies have been conducted, and thus direct comparisons cannot be made between these agents.