Table 1.
A Summary of the Phase 3 Clinical Trials of Covalent BTK Inhibitors
| Trial | Treatments | ORR | mPFS (HR) | mOS (HR) | AE G3 or Higher | Discontinuation Due to AE |
|---|---|---|---|---|---|---|
| RR-CLL | ||||||
| RESONATE31 | Ib vs Ofa | 43% vs 4% | NR vs 8 mos (0.22) | NR vs NR (0.43) | 57% vs 47% | 4% vs 4% |
| ASCEND10 | Acala vs IdR/BR | 83% vs 84% | NR vs 17 mos (0.28) | NR vs NR (0.69) | 68% (Acala) vs 92% (IdR) vs 49% (BR) | 23% (Acala) vs 56% (IdR/BR) |
| ELEVATE-RR42 | Acala vs Ib | 81% vs 77% | 38 mos vs 38 mos (1.00) | NR vs NR (0.82) | 69% vs 75% | 15% vs 21% |
| ALPINE12 | Zanu vs Ib | 84% vs 74% | NR vs 34 mos (0.65) | NR vs NR (0.76) | 67% vs 70% | 16% vs 23% |
| TN-CLL | ||||||
| RESONATE-232 | Ib vs Chl | 86% vs 35% | NR vs 19 mos (0.16) | NR vs NR (HR 0.16) | Neutropenia: 10% vs 18%, Hypertension: 4% vs 0%, Diarrhea: 4% vs 0% | 9% vs 23% |
| Alliance A04120235 | Ib vs BR | 93% vs 81% | NR vs 43 mos (0.39) | NR vs NR | Hematologic: 41% vs 61% Non-hematologic: 74% vs 63% |
NA |
| IbR vs BR | 94% vs 81% | NR vs 43 mos (0.38) | NR vs NR | Hematologic: 39% vs 61% Non-hematologic: 74% vs 63% |
NA | |
| ECOG-ACRIN E191233 | IbR vs FCR | 96% vs 81% | 3y-PFS: 89% vs 73% (0.35) | 3y-OS: 99% vs 92% (0.17) | 80% vs 80% | NA |
| FLAIR36 | IbR vs FCR | (At 9 mos) 91% vs 88% | NR vs 67 mos (0.44) | NR vs NR (1.01) | Febrile neutropenia: 1% vs 4%, Hypertension: 2% vs <1%, Diarrhea: 2% vs 2% | NA |
| iLLUMINATE34 | IbObi vs ChlObi | 91% vs 81% | NR vs 22 mos (0.25) | NR vs NR (1.08) | Neutropenia: 36% vs 46%, Hypertension: 4% vs 3%, Diarrhea: 3% vs 0% | NA |
| ELAVATE-TN11 | AcalaObi vs ChlObi | 94% vs 79% | NR vs 23 mos (0.10) | NR vs NR (0.47) | 70% vs 70% | 11% vs 14% |
| Acala vs ChlObi | 86% vs 79% | NR vs 23 mos (0.20) | NR vs NR (0.60) | 50% vs 70% | 9% vs 14% | |
| SEQUOIA13 | Zanu vs BR | 95% vs 85% | NR vs NR (0.42) | NR vs NR (1.07) | 53% vs 80% | 8% vs 14% |
Abbreviations: Acala, acalabrutinib; AE, adverse event; BTK, Bruton tyrosine kinase; BR, bendamustine + rituximab; Chl, chlorambucil; CLL, chronic lymphocytic leukemia; FCR, fludarabine + cyclophosphamide + rituximab; G3, grade 3; HR, hazard ratio; Ib, ibrutinib; IbR, ibrutinib + rituximab; IdR, idelalisib + rituximab; mos, months; mOS, median overall survival; mPFS, median progression free survival; NA, not available; NR, not reached; Obi, obinutuzumab; Ofa, ofatumumab; ORR, overall response rate; RR, relapsed/refractory; TN, treatment naïve; Zanu, zanubrutinib.