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. 2024 May 27;9:128. doi: 10.1038/s41392-024-01828-x

Table 3.

Therapeutic strategies targeting Notch signaling in clinical trials against human malignancies

Type Agents Cancer Identifier Enrollment (N) Phase Status Country First posted Ref.
γ-Secretase inhibitor RO4929097 Metastatic CRC NCT01116687 37 Phase II Completed United States 2010 506
RO4929097 Previously treated metastatic PDAC NCT01232829 37 Phase II Completed United States 2010 507
RO4929097 Metastatic melanoma NCT01120275 36 Phase II Terminated United States 2010 508
RO4929097 Recurrent platinum-resistant EOC NCT01175343 45 Phase II Completed United States, Canada 2010 509
RO4929097 Recurrent/progressive Glioblastoma NCT00980343 47 Phase II Completed United States 2010 510
RO4929097 Advanced solid tumors NCT01198184 18 Phase Ib Completed Canada 2010 511
RO4929097 Glioma NCT01119599 21 Phase 0/I Completed United States 2010 512
RO4929097 Recurrent malignant glioma NCT01189240 13 Phase I Terminated United States 2010 513
RO4929097 Metastatic breast cancer NCT01149356 15 Phase Ib Terminated United States 2010 N/A
RO4929097 Advanced sarcoma NCT01154452 78 Phase Ib/II Completed United States 2010 514
MK-0752 PDAC NCT01098344 44 Phase I Completed United Kingdom 2010 518
MK-0752 Advanced solid tumors NCT01243762 47 Phase I Terminated USA, Canada, Israel 2010 520
MK-0752 Advanced solid tumors NCT01295632 28 Phase I Completed United States; France; etc. 2011 519
Crenigacestat (LY3039478) Advanced or metastatic ACC NCT01695005 22 Phase I Completed United States, Denmark, etc. 2012 521
Crenigacestat Advanced or metastatic cancer NCT01695005 28 Phase I Completed United States, Denmark, etc. 2012 522
Crenigacestat Advanced or metastatic solid tumors NCT02784795 63 Phase Ib Completed United States, Denmark, etc. 2016 523
Crenigacestat Advanced solid tumors NCT02836600 16 Phase I Completed Japan 2016 524
Crenigacestat Advanced or metastatic solid tumors NCT02784795 31 Phase Ib Completed United States, Denmark, etc. 2016 525
Crenigacestat T-ALL and T-LLy NCT02518113 36 Phase I Completed United States, France, etc. 2015 527
PF-03084014 T-ALL and T-LLy NCT00878189 8 Phase I Completed United States, Italy 2009 528
PF-03084014 Advanced solid malignancies NCT00878189 64 Phase I Completed United States, Italy 2009 526
AL101 TNBC NCT04461600 67 Phase II Active, not recruiting United States, Belgium, etc. 2020 N/A
AL101 ACC NCT04973683 14 Phase Ib Recruiting Texas 2021 N/A
Selective γ-secretase inhibitor BMS-986115 Advanced solid tumors NCT01986218 36 Phase I Terminated United States, Australia, etc. 2013 529
LY900009 Advanced cancer NCT01158404 35 Phase I Completed United States 2010 530
Nirogacestat (PF-03084014) Desmoid tumor/aggressive fibromatosis NCT03785964 142 Phase 3 Active, not recruiting United States, Belgium, etc. 2019 531
ADAM inhibitor INCB7839 Metastatic HER2+ breast cancer NCT01254136 20 Phase I/II Terminated United States 2010 N/A
INCB7839 HER2-positive metastatic breast cancer NCT00864175 68 Phase I/II Terminated India 2007 N/A
INCB7839 Recurrent/ progressive high-grade gliomas NCT04295759 13 Phase I Active, not recruiting United States 2020 N/A
mAb targeting Notch1 Brontictuzumab (OMP-52M51) Solid tumors NCT01778439 48 Phase I Completed United States 2013 535
Cross-reactive antibody targeting Notch2/3 Tarextumab (OMP-59R5) Solid tumors NCT01277146 42 Phase I Completed United States 2010 536
Tarextumab Untreated metastatic PC NCT01647828 177 Phase II Completed United States 2012 537
ADC targeting Notch3 PF-06650808 Breast cancer and other advanced solid tumors NCT02129205 40 Phase I Terminated United States 2014 538
ADC targeting DLL3 Rovalpituzumab tesirine (Rova-T) Recurrent SCLC NCT01901653 82 Phase I Completed United States 2013 539
Rovalpituzumab tesirine Advanced, recurrent SCLC NCT03086239 29 Phase I Completed Japan 2017 540
Rovalpituzumab tesirine Extensive-stage SCLC NCT02819999 28 Phase I Terminated United States 2016 541
Rovalpituzumab tesirine DLL3-expressing, relapsed/refractory SCLC NCT02674568 342 Phase II Completed United States, France, etc. 2016 542
Rovalpituzumab tesirine Previously-treated extensive-stage SCLC NCT03026166 42 Phase I-II Terminated United States, France, etc. 2017 543
Rovalpituzumab tesirine Extensive-stage SCLC NCT03033511 748 Phase III Terminated United States, Australia, etc. 2017 544
Rovalpituzumab tesirine DLL3-high SCLC NCT03061812 444 Phase III Completed United States, Australia, etc. 2017 545
Rovalpituzumab tesirine DLL3-expressing advanced solid tumors NCT02709889 200 Phase I/II Terminated United States 2016 546
SC-002 Relapsed or refractory SCLC and LCNEC NCT02500914 35 Phase I Terminated United States 2015 547
BiTE targeting DLL3 Tarlatamab (AM757) SCLC NCT03319940 392 Phase I Recruiting United States, Australia, etc. 2017 N/A
TriTAC targeting DLL3 HPN328 Advanced cancers NCT04471727 162 Phase I/II Recruiting United States 2020 N/A
mAb targeting DLL4 Enoticumab (REGN421) Advanced solid tumors NCT00871559 83 Phase I Completed United States 2009 548
Demcizumab (OMP-21M18) Previously-treated solid tumors NCT00744562 42 Phase I Completed United States 2008 549
Demcizumab (OMP-21M18) Metastatic non-squamous NSCLC NCT01189968 46 Phase Ib Completed Australia, New Zealand, etc. 2010 550
Demcizumab (OMP-21M18) Platinum-resistant EOC NCT01952249 20 Phase Ib Terminated United States 2013 551
Notch transcription complex inhibitor CB-103 Advanced or metastatic solid tumors and hematological malignancies NCT03422679 79 Phase I/II Terminated United States, France, etc. 2017 553

CRC colorectal cancer, PDAC pancreatic ductal adenocarcinoma, EOC epithelial ovarian cancer, ACC adenoid cystic carcinoma, T-ALL T cell acute lymphoblastic leukemia, T-LLy T cell lymphoblastic lymphoma, TNBC triple-negative breast cancer, PC pancreatic cancer, SCLC small cell lung cancer, LCNEC large cell neuroendocrine carcinoma, ADAM a disintegrin and metalloprotease, mAb monoclonal antibody, ADC antibody-drug conjugate, BiTE bispecific T cell engager, TriTAC tri-specific T cell activating construct, DLL3 delta-like ligand 3