Table 2.
Landmark Clinical Trials of Novel PIs.
| Investigator [Ref.] Study |
Phase | Disease Status | #Prior Therapies Allowed | Treatment | Dosing Schedule of PI | N | Survival End-Point (Months or %) | ORR | ≥VGPR Rate | Median Number of Prior Therapies | Prior Exposure | AEs |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Siegel DS [36] PX-171-003-A1 |
II | RRMM | ≥2 | K (single-agent) | 20/27 mg/m2 days 1, 2, 8, 9, 15, 16 q28days | 266 | mPFS 3.7, mOS 15.6 |
23.7% | 5.5% | 5 | Prior BTZ 99.6% (73% refractory), prior AHCT 74% | NR |
|
Dimopoulos MA [37] ENDEAVOR |
III | RRMM | 1–3 | Kd vs. Vd | 20/56 mg/m2 days 1, 2, 8, 9, 15, 16 q28days | 929 | mPFS 18.7 vs. 9.4 | 77% vs. 63% | 54% vs. 29% | 2 | Previous BTZ 54% vs. 54% |
SAE: 48% vs. 36% |
|
Stewart AK [38] ASPIRE |
III | RRMM | 1–3 | KRd vs. Rd | 20/27 mg/m2 days 1, 2, 8, 9, 15, 16 q28days | 792 | mPFS 26.3 vs. 17.6 | 87% vs. 67% | 70% vs. 40% | 2 | Previous BTZ 66% vs. 66% | SAE: 60% vs. 54% |
|
Berenson JR [39] CHAMPION |
I/II | RRMM | 1–3 | Kd | MTD 70 mg/m2 days 1, 8, 15 q28days | 116 | mPFS 12.6 | 77% | 33% | 1 | BTZ-refract 55% | SAE: 35% |
|
Hajek R [40] FOCUS |
III | RRMM | ≥3 | K vs. d (+Cy) | 20/27 mg/m2 days 1, 2, 8, 9, 15, 16 q28days | 315 | mPFS 3.7 vs. 3.3, mOS 10.2 vs. 10 |
19% vs. 11% | 5 | SAE: 59% vs. 51% | ||
| Sonneveld P [41] | II | NDMM | - | KTd | 20/27–56 mg/m2 days 1, 2, 8,9, 15, 16 q28days | 91 | 3-year PFS 72% | 90% | 68% after 4 cycles 89% after consolidat-ion |
- | - | SAE: 40% |
|
Mikhael JR [42] CYKLONE |
I/II | NDMM | - | KCyTd | MTD of 20/36 mg/m2 IV d1,2,8,9,15,16 q28d | 64 | 2-year PFS 76% and OS 96% | 91% | 69% | G ≥ 3 AE: 67% | ||
| CLARION (unpublished) | III | NDMM, AHCT-ineligible | - | KMP vs. VMP | CFZ 20/36 mg/m2 IV days 1, 2, 8, 9, 22, 23, 29, 30 q42days | 955 | mPFS 22.3 vs. 22.1 | NR | NR | - | - | G ≥ 3 AEs: 75% vs. 76% |
| Bringhen S [43] | II | NDMM, AHCT-ineligible | - | KCyd | 20/36 mg/m2 IV d1, 2, 8, 9, 15, 16 q28days | 58 | 2-year PFS 76%, OS 87% | 95% | 71% | - | - | SAE: 28% |
| Jakubowiak AJ [44] | I/II | NDMM, AHCT-eligible and ineligible | - | KRd | 20/20–36 mg/m2 IV d1, 2, 8, 9, 15, 16 q28days | 53 | 3-year PFS 79.6%, OS 100% | 100% | 91% | - | - | NR |
|
Moreau P [45] TOURMALINE-MM1 |
III | RRMM | 1–3 | IRd vs. Placebo-Rd | 4 mg PO d1, 8, 15 q28d | 722 | mPFS 20.6 vs. 14.7 | 78% vs. 72% | 48% vs. 39% | 1; Prior auto 59% vs. 55% |
Prior BTZ 69% vs. 69% Prior IMId 54% vs. 56% |
SAE: 47% vs. 49% |
Abbreviations: K: carfilzomib, V: bortezomib, Kd: carfilzomib-dexamethasone, Vd: bortezomib-dexamethasone, R: lenalidomide, d: low-dose dexamethasone, Cy: cyclophosphamide, M: melphalan, T: thalidomide, I: ixazomib, mPFS: median progression-free survival, mOS: median overall survival, ORR: overall response rate, VGPR: very good partial response, CR: complete response, RRMM: relapse/refractory multiple myeloma, NDMM: newly diagnosed multiple myeloma, AE: adverse events, SAE: serious adverse events, G: grade, MTD: maximum tolerated dose, AHCT: autologous hematopoietic cell transplantation, IMiD: immunomodulatory drug, NR: not reported.