Skip to main content

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]
  1. TN treatment naïve, R/R relapsed/refractory, WM Waldenstrom's macroglobulinemia, IR ibrutinib and rituximab, RTX rituximab, MR major response, CR complete response, CRi complete response with incomplete hematologic recovery, VGPR very good partial response, PFS progression free survival, OS overall survival, mon months, CLL/SLL chronic lymphocytic leukemia/small lymphocytic lymphoma, BR bendamustine and rituximab, ORR overall response rate, yr years, FCR fludarabine, cyclophosphamide, and rituximab, MCL mantle cell lymphoma, non-GCB Non-germinal center B cell, R-CHOP rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone