LBA55 Trastuzumab deruxtecan (T-DXd) in patients (Pts) with HER2-mutant metastatic non-small cell lung cancer (NSCLC): Interim results from the phase 2 DESTINY-Lung02 trial

Abstract

In DESTINY-Lung01, T-DXd 6.4 mg/kg (a HER2-targeting antibody-drug conjugate) showed durable activity in pts with previously treated HER2-mutant (HER2m) NSCLC (Li et al. N Engl J Med 2022). DESTINY-Lung02 assessed the benefit-risk profile of T-DXd doses 5.4 and 6.4 mg/kg in pts with previously treated HER2m metastatic NSCLC (NCT04644237). Here we report interim results for DESTINY-Lung02. This was a blinded, randomized, non-comparative, phase 2 trial. Pts were randomized 2:1 to T-DXd 5.4 or 6.4 mg/kg Q3W, respectively. The primary endpoint was confirmed objective response rate (cORR) by blinded independent central review (BICR). Secondary endpoints included duration of response (DoR) by BICR, confirmed disease control rate (cDCR) and safety. The prespecified early cohort (PEC; pts randomized ≥4.5 months [mo] before data cutoff [DCO]) was defined to include pts with postbaseline tumor assessments. The safety analysis set (SAS) was all randomized pts who received ≥1 dose of T-DXd. The study was not powered to statistically compare the doses. At DCO (03/24/2022), 52 and 28 pts in the PEC were randomized and 101 and 50 pts in the SAS were treated with T-DXd 5.4 or 6.4 mg/kg, respectively. Median follow-up duration was 5.6/5.4 mo and 3.8/3.9 mo. In the PEC, cORR was 53.8% (95% CI, 39.5-67.8%) and 42.9% (95% CI, 24.5-62.8%) in pts receiving T-DXd 5.4 or 6.4 mg/kg, respectively (Table). Treatment-emergent adverse events (TEAEs) were higher with T-DXd 6.4 mg/kg vs 5.4 mg/kg in the PEC and SAS (median treatment duration: 4.7/5.5 mo and 3.3/3.7 mo). In the SAS, any-grade adjudicated drug-related interstitial lung disease occurred in 5.9% and 14.0% of pts receiving T-DXd 5.4 or 6.4 mg/kg, respectively.Table: LBA55T-DXd in HER2m NSCLCResponse (PEC)5.4 mg/kg n = 526.4 mg/kg n = 28cORR†, n (%)95% CI28 (53.8)39.5-67.812 (42.9)24.5-62.8Complete response (CR)1 (1.9)1 (3.6)Partial response (PR)27 (51.9)11 (39.3)Stable disease (SD)19 (36.5)14 (50.0)Progressive disease2 (3.8)1 (3.6)Nonevaluable (NE)3 (5.8)1 (3.6)cDCR‡, n (%)95% CI47 (90.4)79.0-96.826 (92.9)76.5-99.1DoR, median (95% CI), moNE (4.2-NE)5.9 (2.8-NE)Safety (SAS), %n = 101n = 50Drug-related TEAEsAll-grade92.1100Grade ≥331.758.0Assoc. w/Dose Reduction9.926.0Drug Discontinuation7.916.0Dose Interruption13.930.0†Proportion of pts w/ confirmed CR or PR by BICR.‡Proportion of pts w/ confirmed CR, PR, or SD by BICR. Open table in a new tab †Proportion of pts w/ confirmed CR or PR by BICR. ‡Proportion of pts w/ confirmed CR, PR, or SD by BICR. DESTINY-Lung02 demonstrated clinically meaningful activity with T-DXd 5.4 mg/kg and 6.4 mg/kg in pts with previously treated HER2m NSCLC in the PEC, with a more favorable safety profile with T-DXd 5.4 mg/kg.