Table 1 Published phase III studies of covalent BTK inhibitors in B cell malignancies
From: Targeting Bruton tyrosine kinase using non-covalent inhibitors in B cell malignancies
Drug | Number | Patients | Regimen | Response rates | Survival |
|---|---|---|---|---|---|
Ibrutinib | NCT02165397 | TN or R/R WM (n = 150) | IR versus placebo + RTX | IR: MR 72%, CR 3%, VGPR 23%; Placebo plus RTX: MR 32%, CR 1%, VGPR 4% | IR: PFS 68% and OS 86% at 54 mon; placebo plus RTX: PFS 25% and OS 84% at 54 mon [72, 73] |
Ibrutinib | NCT01611090 | R/R CLL/SLL (n = 578) | Ibrutinib + BR versus placebo + BR | Ibrutinib + BR: ORR 87.2%, CR/CRi 38.1%; placebo + BR: ORR 66.4%, CR/CRi: 8.0% | Ibrutinib + BR: PFS 68.0% and OS 81.6% at 3 yr; Placebo + BR: PFS 13.9% and OS 72.9% at 3 yr [74] |
Ibrutinib | NCT01578707 | R/R CLL/SLL (n = 391) | Ibrutinib versus ofatumumab | Ibrutinib: ORR 91%, CR/CRi 11%; ofatumumab: ORR 4.1%, CR/CRi 1%; | Ibrutinib: median PFS 44.1 mon and median OS 67.7 mon; ofatumumab: median PFS 8.0 mon and median OS 65.1 mon [17, 18] |
Ibrutinib | NCT01722487 NCT01724346 | TN CLL/SLL, age ≥ 65 yr (n = 269) | Ibrutinib versus chlorambucil | Ibrutinib: ORR 92%, CR/CRi 30%; chlorambucil: ORR: 37%, CR/CRi 2% | Ibrutinib: PFS 70% and OS 83% at 5 yr; chlorambucil: PFS 12% and OS 68% at 5 yr [8] |
Ibrutinib | NCT01886872 | TN CLL, age ≥ 65 yr (n = 547) | Ibrutinib versus IR versus BR | Ibrutinib: ORR 93%, CR 7% IR: ORR: 94%; CR:12% BR: ORR: 81%; CR:26% | Ibrutinib: PFS 87% and 90% at 2 yr; IR: PFS 88% and OS 94% at 2 yr; BR: PFS 74% and OS 95% at 2 yr [16] |
Ibrutinib | NCT02048813 | TN CLL/SLL, age ≤ 70 yr (n = 529) | IR versus FCR | IR: ORR 95.8%, CR/CRi 17.2% FCR: ORR 81.1%, CR/CRi 30.3% | IR: PFS 89.4% and OS 98.8% at 3 yr FCR: PFS 72.9% and OS: 91.5% at 3 yr [15] |
Ibrutinib | NCT02264574 | TN CLL/SLL (n = 229) | Ibrutinib + GA-101 versus chlorambucil + GA-101 | Ibrutinib + GA-101: ORR 88%, CR/CRi 19%; chlorambucil + GA-101: ORR 73%, CR/CRi 8% | Ibrutinib + GA-101: PFS 79% and OS 86% at 30 mon; chlorambucil + GA-101: PFS: 31% and OS 85% at 30 mon [14] |
Ibrutinib | NCT01646021 | R/R MCL (n = 280) | Ibrutinib versus temsirolimus | Ibrutinib: ORR 72%, CR 19%; temsirolimus: ORR 40% CR 1% | Ibrutinib: median PFS 15.6 mon and median OS 30.3 mon; temsirolimus: median PFS 6.2 mon and median OS 23.5 mon [13] |
Acalabrutinib | NCT02475681 | TN CLL (n = 535) | Acalabrutinib versus acalabrutinib + GA-101 versus chlorambucil + GA-101 | Acalabrutinib: ORR 94%, CR/CRi 24%; acalabrutinib + GA-101: ORR 85%, CR/CRi 1%; chlorambucil + GA-101: ORR 79%, CR/CRi 5%; | Acalabrutinib: PFS 87% at OS 95% at 24 mon; acalabrutinib + GA-101: PFS 93% and OS 95% at 24 mon; chlorambucil + GA-101: PFS 47% and OS 92% at 24 mon [9] |
Ibrutinib zanubrutinib | NCT03053440 | TN or R/R WM with MYD88L265P (n = 201) | Ibrutinib versus zanubrutinib | Ibrutinib: MR 78%, VGPR: 19% zanubrutinib: MR 77%, VGPR 28% | Ibrutinib: PFS 84% and OS 93% at 18 mon; zanubrutinib: PFS 85% and OS 97% at 18 mon [10] |
Ibrutinib | NCT01855750 | TN non-GCB DLBCL (n = 838) | Ibrutinib + R-CHOP versus R-CHOP | Ibrutinib + R-CHOP: ORR 87.3%, CR 67.3%; R-CHOP: ORR 93.1%, CR 68.0% | For age < 60 yr: Ibrutinib + R-CHOP: PFS 77.4% and OS 93.2% at 3 yr; R-CHOP: PFS 66.3% and OS 80.9% at 3 yr For age ≥ 60 yr: Ibrutinib + R-CHOP: PFS 66.8% and OS 76.6% at 3 yr; R-CHOP: PFS 69.6% and OS 81.7% at 3 yr [75] |