Table 2.
Emerging options in metastatic NSCLC previously treated with ICIs.
| Ph. | Treatment | Population | Nr. | Outcomes |
|---|---|---|---|---|
| I/II | Datopotamab Deruxtecan | Previously treated NSCLC unselected for TROP-2 |
180 | ORR 26% mDOR 10.5 months mPFS 6.9 months mOS 10.4 months |
| III | Datopotamab Deruxtecan vs Docetaxel | Pretreated patients with advanced/metastatic NSCLC | 604 | ORR 26.4% vs. 12.8% PFS 4.4 vs. 3.7 months mDoR 7.1 vs. 5.6 months OS 12.4 vs. 11 months |
| I/II | Sacituzumab Govitecan | Previously treated NSCLC unselected for TROP-2 |
54 | ORR 19% mDoR 6 months mPFS 5.2 months mOS 9.5 months |
| II | Tusamitamab Ravtansine | Non-squamous previously treated moderate CEACAM5 high CEACAM5 |
28 64 |
ORR 7.1% ORR 20.3% |
| II | Telisotuzumab Vedotin | Metastatic NSCLC, ≤2 prior lines, ≤1 line of chemotherapy, MET amplification |
136 | No-squamous: ORR 36.5% mDoR 6.9 months Squamous: ORR 11.1% mDoR 4.4 months |
| II | Trastuzumab Deruxtecan 5.4 mg/kg |
HER2 amplified NSCLC | 41 | ORR 34.1% mPFS 6.7 months mOS 11.7 months |
| Trastuzumab Deruxtecan 6.4 mg/kg | 49 | ORR 26.5% mPFS 5.7 months mOS 12.4 months |
||
| Ib/II | Lenvatinib + Pembrolizumab | Previously treated NSCLC | 21 | ORR 33% mDoR 10.9 months mPFS 5.9 months |
| II | Sitravatinib + Nivolumab (no-squamous) |
Non-squamous NSCLC previously treated with chemotherapy and ICIs | 68 | ORR 16% mPFS 6 months mOS 15 months mDoR 13 months |
| II | Cabozantinib + Atezolizumab | Progression to prior ICI and ≤2 prior lines of systemic therapy excluding VEGFR TKI | 81 | ORR 19% mDoR 5.8 months DCR 80% mPFS 4.5 months mOS 13.8 months |
| III | Cabozantinib + Atezolizumab vs. Docetaxel |
Previously treated with chemotherapy and ICIs | 366 | mOS 10.7 vs. 10.5 months mPFS 4.6 vs. 4.0 months ORR 11% vs. 13.3% |
| II | Ramucirumab + Pembrolizumab vs Investigator choice chemotherapy |
Previously treated with chemotherapy and ICIs | 166 | mOS 14.5 vs. 11.6 months mPFS 4.5 vs. 5.2 months ORR 22% vs. 28% mDoR 12.9 vs. 5.6 months |
| I | Vibostolimab + Pembrolizumab | Previously treated NSCLC | 38 | ORR 3% |
| I | Ociperlimab + Tisletizumab |
Pan tumor, previously treated | 24 | 1 PR 9 SD |
| I/Ib | Sabatolimab + Spartalizumab |
Previously treated NSCLC | 6 | 1/6 PR |
| II | Eftilagimod alpha + Pembrolizumab | PD-1/PDL1-resistant NSCLC | 36 | ORR 8.3% DCR 33% |
| I | TILs + Nivolumab | Previous immunotherapy | 20 | 11 pts reduction tumor burden 3 confirmed responses |
| III | Canakimumab + Docetaxel vs. Docetaxel |
Previous chemotherapy + immunotherapy sequential or concomitant | 237 | mOS 10.5 vs. 11.3 months mPFS 4.17 vs. 4.21 months |
| I | Bintrafusp alfa | Previous platinum-based chemotherapy PD-L1 positive PD-L1 high |
80 | ORR 25% ORR 36% ORR 85.7% |
| III | Tedopi vs. Docetaxel or Pemetrexed |
HLA2 + Previous chemotherapy + immunotherapy sequential or concomitant |
118 | mOS 1.1 vs. 7.5 months ORR 8% vs. 18% mPFS 2.7 vs. 3.4 months 6m DCR 25% vs. 24% |
| I | QL1706 | Previously treated NSCLC Immuno naïve |
149 | ORR 14% mDoR NR ORR 24% |
| I | BL-B01D1 | Previously treated NSCLC | 42 | ORR 40.5%, DCR 95.5% |
DCR = Disease Control Rate; mDoR = median Duration of Response; mOS = median Overall Survival; mPFS = median Progression Free Survival; ORR = Overall Response Rate; PR = partial response; pts = patients; SD = stable disease.