Table 2.
Emerging therapeutic strategies and novel targets in SCLC
| Study | Clinical phase | Brain metastasis at baseline | Number | Treatmemt | ORR | PFS (months) | OS (months) | Treatment-related AEs grade ≥ 3 | The most common treatment-related AEs grade ≥ 3 | |
|---|---|---|---|---|---|---|---|---|---|---|
| DLL3 | ||||||||||
| TRINITY (NCT02674568) | phase II | 134 (40%) | 339 | Rovalpituzumab tesirine | 0.42 | 3.5 | 5.6 | 135 (40%) | Thrombocytopenia | 37 (11%) |
| TAHOE (NCT03061812) | phase III | 175 (59%) | 296 | Rovalpituzumab tesirine | 0.15 | 3.0 (HR = 1.51) | 6.3 (HR = 1.46) | 183 (64%) | Dyspnea | 22 (7%) |
| 87 (59%) | 148 | Topotecan | 0.21 | 4.3 | 8.6 | 113 (88%) | Neutropenia | 49 (38%) | ||
| MERU (NCT03033511) | phase III | 54 (15%) | 372 | Rovalpituzumab tesirine | 0.09 | 3.7 (HR = 0.51) | 8.8 (HR = 1.12, P = 0.237) | 217 (59%) | Thrombocytopenia | 34 (9%) |
| 56 (16%) | 376 | Placebo | 0.05 | 1.4 | 9.9 | 111 (30%) | Increased aspartate aminotransferase | 6 (2%) | ||
| NCT03026166 | phase I/II | 21 (70%) | 30 | Rovalpituzumab tesirine + nivolumab | 0.28 | 4.8 | 7.4 | 16 (53%) | Anemia, Pericardial effusion, Pneumonitis, Pleural effusion | 3 (10%) |
| 8 (67%) | 12 | Rovalpituzumab tesirine + nivolumab + ipilimumab | 0.36 | 4.1 | 11 | 11 (92%) | Thrombocytopenia | 3 (25%) | ||
| DeLLphi-300 (NCT03319940) | phase I | 38 (25%) | 152 | Tarlatamab (AMG 757) | 0.25 | 3.5 | 17.5 | 150 (99%) | Cytokine release syndrome | 50 (33%) |
| PARP | ||||||||||
| NCT01638546 | phase II | 12 (22%) | 55 | Temozolomide + veliparib | 0.39 | 3.8 (HR = 0.84; P = 0.390) | 8.2 (P = 0.500) | / | Thrombocytopenia | 27 (50%) |
| 10 (20%) | 49 | Temozolomide + placebo | 0.14 | 2.0 | 7.0 | / | Lymphopenia | 12 (26%) | ||
| NCT02446704 | phase I/II | 20 (40%) | 50 | Olaparib + Temozolomide | 0.42 | 4.2 | 8.5 | / | Neutropenia | 19 (38%) |
| ECOG-ACRIN 2511 (NCT01642251) | phase II | 0 | 64 | Veliparib + cisplatin + etoposide | 0.72 | 6.1 (HR = 0.75; P = 0.060) | 10.3 (HR = 0.83; P = 0.170) | / | Neutropenia | 32 (49%) |
| 0 | 64 | Placebo + cisplatin + etoposide | 0.66 | 5.5 | 8.9 | / | Neutropenia | 21 (32%) | ||
| NCT02289690 | phase II | / | 61 | Veliparib + chemotherapy followed by veliparib maintenance | 0.77 | 5.8 (HR = 0.67; P = 0.059) | 10.1 (HR = 1.43; P = 0.088) | 49 (82%) | Neutropenia | 34 (57%) |
| / | 59 | Veliparib + chemotherapy followed by placebo | 0.59 | 5.7 (HR = 0.98; P = 0.924) | 10.0 (HR = 1.46; P = 0.083) | 51 (88%) | Neutropenia | 32 (55%) | ||
| / | 61 | Placebo + chemotherapy followed by placebo | 0.64 | 5.6 | 12.4 | 41 (68%) | Neutropenia | 24 (40%) | ||
| S1929 (NCT04334941) | phase II | 13 (24%) | 54 | Atezolizumab + talazoparib | 0.11 | 2.9 (HR = 0.66; P = 0.019) | 9.7 (HR = 0.98; P = 0.470) | 30 (57%) | Anemia | 19 (37%) |
| 10 (19%) | 52 | Atezolizumab | 0.19 | 2.4 | 9.5 | 9 (18%) | AST increased | 2 (4%) | ||
| TIGIT | ||||||||||
| SKYSCRAPER-02 (NCT04256421) | phase III | 47(19%) | 243 | Tiragolumab + atezolizumab + carboplatin + etoposide | 0.71 | 5.1 (HR = 1.08) | 12.8 (HR = 1.09; P = 0.421) | 127 (53%) | Rash | 63 (26%) |
| 46 (19%) | 247 | Placebo + atezolizumab + carboplatin + etoposide | 0.66 | 5.4 | 12.9 | 142 (58%) | Rash | 47 (19%) | ||
| B7-H3 | ||||||||||
| IDeate-Lung01 | phase II | 19 (41%) | 46 | I-DXd (DS-7300) 8 mg/kg | 0.26 | 4.2 | 9.4 | 20 (44%) | Neutropenia | 1 (2%) |
| 18 (43%) | 42 | I-DXd (DS-7300) 12 mg/kg | 0.55 | 5.5 | 11.8 | 21 (50%) | Neutropenia | 7 (17%) | ||
| Epigenetic therapies | ||||||||||
| NCT03879798 | phase I/II | / | 21 | Valemetostat (DS-3201b) + irinotecan | 0.21 | 2.2 | 6.6 | / | Anemia | 6 (29%) |
| Other | ||||||||||
| NCT02454972 | phase II | 4 (4%) | 105 | Lurbinectedin | 0.35 | 3.5 | 9.3 | Fatigue | 7 (7%) | |
| ATLANTIS (NCT02566993) | phase III | 46 (15%) | 307 | Lurbinectedin + doxorubicin | 0.32 | 4.0 (HR = 0.83) | 8.6 (HR = 0.97; P = 0.900) | 145 (48%) | Neutropenia | 112 (37%) |
| 49 (16%) | 306 | Topotecan or cyclophosphamide, doxorubicin, and vincristine | 0.29 | 4.0 | 7.6 | 218 (75%) | Neutropenia | 200 (69%) | ||
| LUPER (NCT04358237) | phase I/II | 6 (21%) | 28 | Lurbinectedin + pembrolizumab | 0.46 | 4.6 | 10.5 | 23 (82%) | Neutropenia | 19 (44%) |
| TROPiCS-03 (NCT03964727) | phase II | 5 (12%) | 43 | Sacituzumab govitecan (SG) | 0.42 | 4.4 | 13.6 | 26 (61%) | Neutropenia | 13 (47%) |
Abbreviations: AST, aspartate aminotransferase