Summary of midostaurin and avapritinib efficacy and safety outcomes
| . | Midostaurin55 . | Avapritinib57 . |
|---|---|---|
| Trial design | Phase 2, single arm, open label | Phase 1, dose escalation and expansion |
| Patients, n | 116 | Dose escalation, 37 |
| Dose extension, 32 | ||
| Evaluable for response, n | 89 | 39 |
| Response criteria | Modified Valent and modified Cheson* | Modified IWG-MRT-ECNM† |
| ORR, % | 60 (MR + PR) | 77 (CR + CRh + PR + CI) |
| Response subcategory, % | MR 45 | CR 8 |
| CR 0 | CRh 15 | |
| Incomplete remission 21 | PR 46 | |
| Pure clinical response 17 | CI 8 | |
| Unspecified 7 | SD 23 | |
| PR 15 | PD 0 | |
| SD 12 | ||
| PD 11 | ||
| Not evaluable 17 | ||
| Note: 26% of patients previously treated with midostaurin | ||
| Post hoc exploratory efficacy analysis by IWG-MRT-ECNM criteria using algorithmic approach, %† | ||
| FDA (CR + PR) | 17 (CR [2] + PR [15]) | Not applicable |
| EMA (CR + PR + CI) | 28 (CR [1] + PR [15] + CI [12]) | |
| Response rate by advSM subgroup, % | ||
| ASM | 75 | 100 |
| SM-AHN | 58 | 75 |
| MCL | 50 | 75 |
| Patients with ≥50% decrease in BM MCs, % | 57 | 93 |
| Patients with ≥50% decrease in serum tryptase, % | 60 | 100 |
| Evaluable patients with ≥35% decrease in spleen volume, % | 26 | 81 |
| AE profile (any grade/grade 3-4), % | Nausea 79/6 | Periorbital edema 75/4 |
| Vomiting 66/6 | Diarrhea 41/1 | |
| Diarrhea 54/8 | Nausea 38/4 | |
| Peripheral edema 34/4 | Fatigue 36/7 | |
| Abdominal pain 28/3 | Peripheral edema 33/0 | |
| Fatigue 28/9 | Vomiting 32/4 | |
| Pyrexia 27/6 | Cognitive effects 32/4 | |
| Constipation 24/1 | Hair color changes 29/1 | |
| Headache 23/2 | Arthralgia 20/1 | |
| Neutropenia 48/24 | Neutropenia 12/10 | |
| Anemia 63/41 | Anemia 55/29 | |
| Thrombocytopenia 52/29 | Thrombocytopenia 35/23 | |
| Intracranial bleeding (ICB) in 7 patients; 5 of 7 resumed therapy; 1 ICB in setting of severe head trauma; dose modifications for thrombocytopenia instituted to mitigate ICB |
| . | Midostaurin55 . | Avapritinib57 . |
|---|---|---|
| Trial design | Phase 2, single arm, open label | Phase 1, dose escalation and expansion |
| Patients, n | 116 | Dose escalation, 37 |
| Dose extension, 32 | ||
| Evaluable for response, n | 89 | 39 |
| Response criteria | Modified Valent and modified Cheson* | Modified IWG-MRT-ECNM† |
| ORR, % | 60 (MR + PR) | 77 (CR + CRh + PR + CI) |
| Response subcategory, % | MR 45 | CR 8 |
| CR 0 | CRh 15 | |
| Incomplete remission 21 | PR 46 | |
| Pure clinical response 17 | CI 8 | |
| Unspecified 7 | SD 23 | |
| PR 15 | PD 0 | |
| SD 12 | ||
| PD 11 | ||
| Not evaluable 17 | ||
| Note: 26% of patients previously treated with midostaurin | ||
| Post hoc exploratory efficacy analysis by IWG-MRT-ECNM criteria using algorithmic approach, %† | ||
| FDA (CR + PR) | 17 (CR [2] + PR [15]) | Not applicable |
| EMA (CR + PR + CI) | 28 (CR [1] + PR [15] + CI [12]) | |
| Response rate by advSM subgroup, % | ||
| ASM | 75 | 100 |
| SM-AHN | 58 | 75 |
| MCL | 50 | 75 |
| Patients with ≥50% decrease in BM MCs, % | 57 | 93 |
| Patients with ≥50% decrease in serum tryptase, % | 60 | 100 |
| Evaluable patients with ≥35% decrease in spleen volume, % | 26 | 81 |
| AE profile (any grade/grade 3-4), % | Nausea 79/6 | Periorbital edema 75/4 |
| Vomiting 66/6 | Diarrhea 41/1 | |
| Diarrhea 54/8 | Nausea 38/4 | |
| Peripheral edema 34/4 | Fatigue 36/7 | |
| Abdominal pain 28/3 | Peripheral edema 33/0 | |
| Fatigue 28/9 | Vomiting 32/4 | |
| Pyrexia 27/6 | Cognitive effects 32/4 | |
| Constipation 24/1 | Hair color changes 29/1 | |
| Headache 23/2 | Arthralgia 20/1 | |
| Neutropenia 48/24 | Neutropenia 12/10 | |
| Anemia 63/41 | Anemia 55/29 | |
| Thrombocytopenia 52/29 | Thrombocytopenia 35/23 | |
| Intracranial bleeding (ICB) in 7 patients; 5 of 7 resumed therapy; 1 ICB in setting of severe head trauma; dose modifications for thrombocytopenia instituted to mitigate ICB |
CI, clinical improvement; CR, complete response; CRh, CR with partial hematologic recovery; EMA, European Medicines Agency; FDA, US Food and Drug Administration; IWG, International Working Group; MR, major response; MRT, Myeloproliferative Neoplasms Research and Treatment; ORR, overall response rate; PD, progressive disease; PR, partial response; SD, stable disease.
Responses need to be confirmed for 8 wk.
Responses need to be confirmed for 12 wk.