Table 1.
Studies of Antibody Drug Conjugates in HER2 altered NSCLC.
| Drug | Trial | Tumor Types | NSCLC Population (n) | Overall Response Rate | Median PFS (Months) | Median OS (Months) | Ref |
|---|---|---|---|---|---|---|---|
| T-DXd | phase I | NSCLC, colorectal, salivary gland, breast, esophageal, endometrial, Paget’s disease, biliary tract, pancreatic, cervical, extraskeletal myxoid chondrosarcoma, small intestine adenocarcinoma | HER2 IHC ≥ 1+ or HER2 mutation (NSCLC n = 18; exon 20 NSCLC n = 8) |
Overall NSCLC: 55.6% HER2 mutant: 72.7% |
Overall NSCLC: 11.3 HER2 mutant: 11.3 |
Overall NSCLC: n/r HER2 mutant: 17.3 |
[17] |
| T-Dxd | phase II (DESTINY-Lung01) | NSCLC | HER2 IHC 2/3+ (n = 49) |
24.5% | 5.4 | n/a | [18] |
| T-DXd | phase II (DESTINY-Lung01) | NSCLC |
HER2 mutation (n = 91; exon 20 = 78) |
55% | 8.2 | 17.8 | [19] |
| T-DM1 | phase II | NSCLC |
HER2 mutation (n = 18; exon 20 = 11) |
44% | 5.0 | n/a | [20] |
| T-DM1 | phase II | NSCLC | HER2 (IHC 3+, IHC 2+ and FISH HER2/CEP17 ratio ≥ 2, or exon 20 mutation) (n = 15, IHC/FISH+ n = 8, exon 20 n = 7) |
Overall: 6.7% IHC/FISH-positive: 0% Exon 20: 14.3% |
2.0 | 10.9 | [21] |
| T-DM1 | phase II | NSCLC | HER2 IHC 2/3+ (n = 49) |
IHC 2+: 0% IHC 3+: 20% |
IHC 2+: 2.6 IHC 3+: 2.7 |
IHC 2+: 12.2 IHC 3+: 15.3 |
[22] |
| T-DM1 | phase II | NSCLC |
HER2 exon 20 mutation (n = 22) |
38.1% | 2.8 | 8.1 | [23] |
PFS: progression free survival; OS: overall survival; T-DM1: Trastuzumab Emtansine; T-DXd: Trastuzumab Deruxtecan; IHC: immunohistochemistry; CEP17: chromosome enumeration probe 17; n/a: not available; n/r: not reached.