Table 2.
Summary of current key antibody-drug conjugate (ADC) clinical data in metastatic NSCLC.
| Trastuzumab deruxtecan (NCT03505710) in HER2-mutant tumors | |
|---|---|
| Linker type - cleavable tetrapeptide-based linker Antibody subclass - IgG1 | |
| FDA-approval - August 11 2022 On August 11, 2022, for NSCLC patients with activating human HER2 mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. | |
| Outcome | Trastuzumab deruxtecan (n = 91) |
| ORR (95% CI) | 55% (44-65) |
| CR | 1 (1%) |
| PR | 49 (54%) |
| SD | 34 (37%) |
| PD | 3 (3%) |
| Median DOR, months (95% CI) | 9.3 months (5.7–14.7) |
| Median PFS, months (95% CI) | 8.2 (6.0–11.9) |
| Median OS, months (95% CI) | 17.8 (13.8–22.1) |
| Median time to response, months (range) | 1.5 (1.2–9.3) |
| Trastuzumab deruxtecan (NCT03505710) in tumors with HER2 overexpression | ||
|---|---|---|
| Antibody subclass–IgG1 Linker type - cleavable tetrapeptide-based linker | ||
| Outcome | Total population (n = 49) | |
| ORR (95% CI) | 24.5% (13.3–38.9) | |
| Median PFS, months (95% CI) | 5.4 (2.8–7.0) | |
| Median OS, months (95% CI) | 11.3 (7.8-NE) | |
| IHC 2 + (n = 39) | IHC 3 + (n = 10) | |
| ORR (95% CI) | 25.6% (13.0–42.1) | 20% (2.5–55.6) |
| SD | 41% | 60% |
| DCR | 66.7% (49.8%–80.9%) | 80.0% (44.4%–97.5%) |
| DOR, months (range) | 5.8 (3.2-NE) | 6.0 (NE-NE) |
| Patritumab deruxtecan (NCT03260491) | ||
| Outcome | Patritumab deruxtecan 5.6 mg/kg (n = 56) | |
| ORR (95% CI) | 25% (14.4–38.4) | |
| CR | 2% | |
| PR | 23% | |
| SD | 45% | |
| Median DOR, months (range) | 7 (3–7) | |
| Datopotamab-deruxtecan (NCT03401385) | |||
|---|---|---|---|
| Antibody subclass–IgG1 Linker type - cleavable tetrapeptide-based linker | |||
| Outcome | 4 mg/kg (n = 40) | 6 mg/kg (n = 39) | 8 mg/kg (n = 80) |
| ORR (95% CI) | 23% (n = 9) | 21% (n = 8) | 25% (n = 20) |
| Confirmed CR/ PR | n = 7 | n = 6 | n = 19 |
| PD | 15% | 21% | 9% |
| DCR | 73% | 67% | 80% |
| Telisotuzumab vedotin (NCT03539536) | ||||
|---|---|---|---|---|
| Antibody subclass–IgG1 Linker type - Cleavable dipeptide | ||||
| Outcome | EGFR mutant (n = 37) | Non-squamous EGFR WT cohort (n = 37) | c-Met–intermediate (n = 13) | c-Met–high (n = 13) |
| ORR (95% CI) | 13.3% (3.8–30.7) | 35.1% (20.2–52.5) | 25% (9.8–46.7) | 53.8% (25.1–80.8) |
ADC antibody-drug conjugate, CR complete response, DCR disease control rate, DOR duration of response, NE not estimable, NSCLC non-small cell lung cancer, ORR objective response rate, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, SD stable disease.