Table 1 Completed and ongoing clinical trials of DLL3-targeting therapies for SCLCa
From: Emerging therapies targeting the delta-like ligand 3 (DLL3) in small cell lung cancer
Agent | Mechanism of action | Statusb/trial identifier | Indications | Sponsor |
|---|---|---|---|---|
ADCs | ||||
Rovalpituzumab tesirine | ADC targeting DLL3 | Completed NCT02674568 (phase 2) NCT01901653 (phase 1/2) NCT02874664 (phase 1) NCT03061812 (phase 3) NCT03086239 (phase 1) | Relapsed/refractory/recurrent/extensive-stage/advanced/metastatic SCLC/delta-like protein 3–expressing advanced solid tumors | AbbVie/Stemcentrx |
Terminated or withdrawn NCT02819999 (phase 1) NCT03026166 (phase 1/2) NCT03033511 (phase 3) NCT03334487 (phase 3) NCT02709889 (phase 1/2) | ||||
SC-002 | ADC targeting DLL3 | Terminated NCT02500914 (phase 1) | Relapsed SCLC or large cell NEC | Stemcentrx |
CAR therapies | ||||
DLL3-CAR-NK cells | Anti-DLL3–transduced NK cells | Recruiting NCT05507593 (phase 1) | Relapsed/refractory extensive-stage SCLC | Tianjin Medical University Cancer Institute and Hospital |
AMG 119 | Anti-DLL3–transduced autologous T cells | Suspended NCT03392064 (phase 1) | Relapsed/refractory SCLC | Amgen Inc |
T-cell engagers | ||||
Tarlatamab | Half-life–extended DLL3 x CD3 bispecific T-cell engager | Recruiting NCT03319940 (phase 1; DeLLphi-300) NCT05060016 (phase 2; DeLLphi-301) Active, not recruiting NCT04885998 (phase 1; DeLLphi-302) Not yet recruiting NCT05740566 (phase 3; Dellphi-304) | Relapsed/refractory SCLC | Amgen Inc |
Recruiting NCT05361395 (phase 1; DeLLphi-303) | First-line treatment for extensive-stage SCLC | Â | ||
BI 764532 | DLL3/CD3 T-cell–engaging bispecific antibody | Recruiting NCT04429087 (phase 1) | Refractory, DLL3-expressing SCLC and other neuroendocrine neoplasms | Boehringer Ingelheim |
HPN328 | Tri-specific recombinant protein construct | Recruiting NCT04471727 (phase 1/2) | Relapsed/refractory, advanced DLL3-expressing malignancies | Harpoon Therapeutics |
RO7616789 | DLL3 x CD3/CD137 multispecific antibody | Recruiting NCT05619744 (phase 1) | Relapsed extensive-stage SCLC or high-grade NEC of any other origin | Hoffmann-La Roche |
PT217 | Anti-DLL3 x anti-CD47 bispecific antibody | Not yet recruiting NCT05652686 (phase 1) | Advanced or metastatic relapsed/refractory SCLC, large cell NEC, neuroendocrine prostate cancer, and gastroenteropancreatic neuroendocrine tumors | Phanes Therapeutics |
QLS31904 | Anti-DLL3 x anti-CD3 bispecific antibody | Recruiting NCT05461287 (phase 1) | Patients with advanced solid tumors, including SCLC, who progress on or are intolerant to standard of care, or have no effective standard therapeutic regimen | Qilu Pharmaceutical |