Table 3.
Selected active or recruiting clinical trials of novel inhibitors of BCL2/BTK/PI3K proteins or TAAs (CD19/CD20/CD22/CD38), evaluated alone or in combination as first- or second-line therapies for B cell malignancies.
| Drug | Class | Disease Setting | Phase | Study | References |
|---|---|---|---|---|---|
| BGB-11417 | Bcl-2 inhibitor | CLL/SLL, B-NHL |
I |
NCT04277637 Recruiting, 2020–2023 Alone or combined with zanubrutinib |
[76] |
| Lisaftoclax/ APG-2575 |
Bcl-2/Bcl-xL inhibitor | CLL/SLL, MZL, MCL CLL/SLL |
I Ib/II |
NCT03913949 Recruiting, 2019–2023 NCT04494503 Recruiting, 2020–2023 Alone or combined with rituximab or ibrutinib |
[77] [123] |
| PRT1419 | Mcl-1 inhibitor | R/R MM R/R B-NHL |
I |
NCT04543305 Active, 2020–2022 |
[124] |
|
S64351/ MIK-665 |
Mcl-1 inhibitor | AML | I/II |
NCT04629443 Recruiting, 2020–2024 + azacytidine |
|
| Orelabrutinib /ICP-022 |
BTK inhibitor | MCL CLL/SLL FL, MZL, MCL, CLL/SLL R/R MZL, R/R WM, DLBCL |
I/II I/II II |
NCT03494179 NCT03493217 Active, 2018–2022 NCT04014205 Recruiting, 2019- NCT03797456 NCT04440059 NCT04438005 Recruiting, 2020- |
[125] |
| Nemtabrutinib/ MK-1026/ARQ-531 |
BTK inhibitor | CLL/SLL, MCL, R/R MZL R/R FL, R/R WM | II |
NCT04728893 Recruiting, 2021–2027 |
|
| Pirtobrutinib/ LOX-305 |
BK inhibitor | Previously treated CLL/SLL, WM, MCL, MZL Untreated CLL/SLL Previously treated CLL/SLL |
I/II III III |
NCT03740529 Recruiting, 2018–2023 Combined with venetoclax + rituximab NCT05023980 Recruiting 2021- NCT04965493 Recruiting, 2021- Combined with venetoclax + rituximab |
|
| Parsaclisib/INCB500465/ IBI-376 |
PI3Kδ inhibitor | CLL, DLBCL | I/II |
NCT04809467 Recruiting, 2021–2023 Alone or combined with tafasitamab |
|
| Zandelisib/PWT143/ME-401 | PI3Kδ inhibitor | R/R FL, R/R MZL R/R CLL |
III II |
NCT04745832 Recruiting, 2021–2031 Combined with rituximab NCT05209308 Recruiting, 2022–2026 Combined with rituximab + venetoclax |
[126] |
| BGB-10188 | PI3Kδ inhibitor | R/R CLL, FL, MCL, DLBCL, MZL | I/II |
NCT04282018 Recruiting, 2020–2025 Alone or combined with zanubrutinib and tiselizumab |
|
| Umbralisib/ TGR-1202 |
Dual PI3Kδ/CK1ε inhibitor |
R/R CLL, R/R MCL R/R CLL, R/R B-NHL |
I/Ib I |
NCT02268851 Active, 2014–2023 Combined with ibrutinib NCT03283137 Active, 2017–2024 Combined with pembrolizumab |
[127] |
| Mosunetuzumab/ BTC4465A |
BiTE anti-CD20/CD3 | CLL, B-NHL B-NHL |
I/II I/II |
NCT02500407 Recruiting, 2015- Alone or combined with atezolizumab (anti-PD-L1) NCT03671018 Recruiting, 2018- Alone or combined with polatuzumab (anti-CD79B-monomethyl auristatin E) |
[128] |
| Odronextamab/ REGN1979 |
BiTE anti-CD20/CD3 | R/R DLBCL, FL, MZL, WM | I/II |
NCT02651662 Active, 2016–2026 Alone or combined with cemiplimab (anti-PD-1) NCT03888105 Recruiting, 2019–2028 |
[129] |
| Epcoritamab/ GEN301 |
BiTE duoBody-anti-CD20/CD3 | R/R or progressive DLBCL, MCL, FL, MZL, SLL R/R DLBCL R/R CLL |
I/II III I/II |
NCT03625037 Recruiting, 2018–2024 NCT04628494 Recruiting, 2020–2024 NCT04623541 Recruiting, 2020–2024 |
[130,131] |
| Glofitamab (RO7082859) | BiTE anti-CD20/CD3 | R/R B-NHL | I/II Ib/II |
NCT03075696 Recruiting, 2017–2023 Alone or combined with obinutzumab NCT03533283 Recruiting, 2018–2024 Alone or combined with atezolizumab, obinutuzumab, tocilizumab polatuzumab vedotin |
[132] |
| Tafasitamab/ MOR208/ |
Anti-CD19 | R/R FL, R/R MZL DLBCL |
III III |
NCT04680052 Recruiting, 2020- Combined with rituximab + lenalidomide compared with rituximab + lenalidomide NCT04824092 Recruiting, 2021–2026 Combined with lenalidomide + R-CHOP |
[133] |
| CAR-20.19-T | Anti-CD19/CD20 CAR-T/CD28/ 4-1BB/CD3ζ |
CLL/SLL, R/R B-NHL | I |
NCT03019055 Active, 2017–2022 |
[134] |
| CD19-CAR-NK using blood cord NKs |
Anti-CD19 CAR-NK/OX40/CD3ζ/IL-15 | B-ALL CLL/SLL, R/R B-NHL |
I/II |
NCT03056339 Active, 2017–2022 after treatment with fludarabine/cyclophosphamide lymphodepletion |
[135,136] |
| NKX019 using peripheral blood NKs |
Anti-CD19 CAR-NK/OX40/ CD3ζ/IL-15 |
B-ALL CLL/SLL, R/R B-NHL |
I |
NCT05020678 Recruiting 2021–2023 |
[137] |
| C-CAR066/CBM.20-CAR-T | Anti-CD20 CAR-T | NHLs resistant to rituximab or anti-CD19 CAR-T | I |
NCT04036019 Recruiting, 2019–2021 NCT04316624 Recruiting, 2020- |
[138] |
| Inotuzumab ozogamicin | ADC anti-CD22- calicheamicin | B-ALL, B-NHL | III |
NCT03959085 Recruiting, 2019–2029 post chemotherapy |
|
| JNJ-75348780 | BiTE anti-CD22/CD3 | CLL, B-NHL | I |
NCT04540796 Recruiting, 2020–2024 |
|
| CD22-CAR | Anti-CD22 CAR-T/CD8/4-1BB/CD3ζ | R/R B-ALL, B-NHL |
I |
NCT02315612 Recruiting, 2014–2040 |
[139] |
| LV20.19 | Bi anti-CD19/CD22 CAR-T/4-1BB/CD3ζ | CLL/SLL, B-NHL | I |
NCT03019055 Active, 2017–2022 |
[134,140] |
| AUTO3 | Bi anti-CD19 (OX40 costim)/CD22 (4-1BB costim) CAR-T | R/R DLBCL | I/II |
NCT03287817 Active 2017- |
[141] |
| CD19-22.BB.z-CAR | Bi anti-CD19/ CD22 CAR-T |
R/R B-ALL, DLBCL Pretreated B-ALL |
I I |
NCT03233854 Recruiting, 2017–2025 Combined with NKTR-255 (IL-15 receptor agonist) NCT03448393 Recruiting, 2018–2040 following cyclophosphamide/fludarabine treatment |
[142] [143] |
| CD20-22 CAR | Bi anti-CD20/CD22 CAR-T | B cell malignancies | I |
NCT04283006 Recruiting, 2020–2028 |
|
| Felzartamab/ MOR202/TJ202 |
Anti-CD38 | R/R MM | II III |
NCT03860038 Active, 2019–2022 Combined with dexamethasone NCT03952091 Active, 2019–2022 Combined with lenalidomide + dexamethasone |
|
| TAK-079 | Anti-CD38 | R/R MM MM |
I/IIa I |
NCT03499280 Completed, 2018–2022 Alone or combined with pomalidomide and dexamethasone NCT03984097 Active, 2019–2023 Combined with lenalidomide + dexamethasone |
|
| TAK-573/ modakafusp |
ADC anti-CD38 delivering attenuated IFN-α2b | R/R MM | I/II |
NCT03215030 Recruiting, 2017- Alone or combined with dexamethasone |
[144] |
| TAK-169/ MT-0169 |
ADC anti-CD38 delivering Shiga-like toxin | R/R B-NHL | I |
NCT04017130 Recruiting, 2019- |
[145] |
| ISB 1342/ GBR 1342 |
BiTE anti-CD38/CD3 | R/R MM | I |
NCT03309111 Recruiting 2017–2024 |