Table 1.
Demographics, baseline characteristics, and prior therapies
| Dose escalation | Dose expansion | Pooled RDEa | All patients | ||||
|---|---|---|---|---|---|---|---|
| Characteristics | 3.2 mg/kg (n = 4) | 4.8 mg/kg (n = 15) | 5.6 mg/kg (n = 12) | 6.4 mg/kg (n = 5) | 5.6 mg/kg (n = 45) | 5.6 mg/kg (n = 57) | All doses (N = 81) |
| Age, median (range), years | 59.5 (51–67) | 56.0 (44–76) | 63.0 (50–77) | 68.0 (60–80) | 66.0 (40–80) | 65.0 (40–80) | 64.0 (40–80) |
| Female, n (%) | 3 (75) | 10 (67) | 8 (67) | 3 (60) | 28 (62) | 36 (63) | 52 (64) |
| Time since first NSCLC diagnosis, median (range), months | 32 (19.8–60.4) | 50 (15.9–121.9) | 31 (11.1–72.2) | 37 (12.7–50.8) | 57 (13.4–141.1)b | 45 (11.1–141.1)c | 45 (11.1–141.1)d |
| ECOG performance status, n (%) | |||||||
| 0 | 2 (50) | 7 (47) | 4 (33) | 2 (40) | 19 (42) | 23 (40) | 34 (42) |
| 1 | 2 (50) | 8 (53) | 8 (67) | 3 (60) | 26 (58) | 34 (60) | 47 (58) |
| Sum of target lesion diameters at baseline, median (range), mme | 37 (30–58) | 44 (10–111) | 50.5 (15–195) | 56 (27–89) | 55 (13–152) | 54 (13–195) | 51.5 (10–195) |
| History of CNS metastases, n (%) | 4 (100) | 8 (53) | 6 (50) | 4 (80) | 21 (47) | 27 (47) | 43 (53) |
| Patients with previously treated CNS metastases | 0 | 0 | 2 (17) | 0 | 13 (29) | 15 (26) | 15 (19) |
| Brain metastasis at baseline | 3 (75) | 5 (33) | 1 (8) | 0 | 8 (18) | 9 (16) | 17 (21) |
| EGFR-activating mutations,fn (%) | |||||||
| Ex19del | 2 (50) | 8 (53) | 5 (42) | 4 (80) | 28 (62) | 33 (58) | 47 (58) |
| L858R | 2 (50) | 5 (33) | 6 (50) | 1 (20) | 14 (31) | 20 (35) | 28 (35) |
| G719X | 0 | 1 (7) | 0 | 0 | 5 (11) | 5 (9) | 6 (7) |
| L861X | 0 | 2 (13) | 0 | 0 | 2 (4) | 2 (4) | 4 (5) |
| Ex19ins | 0 | 0 | 1 (8) | 0 | 0 | 1 (2) | 1 (1) |
| No. of prior lines of systemic therapy in the locally advanced or metastatic setting, median (range) | 4 (2–5) | 4 (2–5) | 2.5 (1–9) | 2 (1–5) | 4 (1–9) | 4 (1–9) | 4 (1–9) |
| Prior cancer regimens, n (%)g | |||||||
| Prior EGFR TKI therapyh | 4 (100) | 15 (100) | 12 (100) | 5 (100) | 45 (100) | 57 (100) | 81 (100) |
| Prior osimertinib | 3 (75) | 15 (100) | 12 (100) | 5 (100) | 37 (82) | 49 (86) | 72 (89) |
| Prior PBC | 2 (50) | 9 (60) | 7 (58) | 2 (40) | 45 (100) | 52 (91) | 65 (80) |
| Prior PBC and osimertinib | 1 (25) | 9 (60) | 7 (58) | 2 (40) | 37 (82) | 44 (77) | 56 (69) |
| Prior immunotherapyi | 2 (50) | 3 (20) | 2 (17) | 0 | 21 (47) | 23 (40) | 28 (35) |
Abbreviation: PBC, platinum-based chemotherapy.
aPooled patients who received the HER3-DXd RDE, including 12 patients in the 5.6-mg/kg group in the dose escalation part and 45 patients in the dose expansion part.
b n = 43.
c n = 55.
d n = 79.
eBy BICR per RECIST 1.1.
fPatients with multiple EGFR-activating mutations are listed in more than one row.
gNo patients received prior treatment with a topoisomerase I inhibitor.
hEGFR TKI therapies included afatinib, dacomitinib, erlotinib, gefitinib, olmutinib, and osimertinib.
iPrior immunotherapies included atezolizumab, ipilimumab, nivolumab, and pembrolizumab.