KEY TAKEAWAYS
- The phase 2 DESTINY-Lung02 trial evaluated two dosages of T-DXd (5.4 mg/kg and 6.4 mg/kg) in patients with pretreated HER2m mNSCLC.
- The trial’s primary endpoint was cORR, and key secondary endpoints were DoR, DCR, PFS, OS, and safety.
- Both dosages demonstrated strong and durable responses with a generally manageable safety profile.
The phase 2 trial involved patients (pts) with pretreated HER2 (ERBB2)-mutant (HER2m) metastatic non-small cell lung cancer (mNSCLC). The pts were randomized (in 2:1) to receive either trastuzumab deruxtecan (T-DXd) 5.4 mg/kg or 6.4 mg/kg every three weeks.
The main goal was to determine the confirmed objective response rate (cORR) through a blinded independent central review (BICR). Important secondary goals included assessing the duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Statistical evaluations were based on comparing the lower limit of the cORR’s 95% confidence interval (CI) with a benchmark ORR of 26.4%. Direct statistical comparisons between the dosages were not intended for this study.
As of December 23, 2022, 102 pts were assigned T-DXd 5.4 mg/kg, and 50 pts were assigned the 6.4 mg/kg dosage. The median follow-up was 11.5 and 11.8 months for the 5.4 mg/kg and 6.4 mg/kg dosages, respectively. BICR-determined cORRs were 49.0% and 56.0% for the two dosages. Similarly, median DoRs, as determined by BICR, were 16.8 months and not estimable for the two dosages, with median PFS being 9.9 months and 15.4 months, respectively. The median treatment durations were 7.7 months and 8.3 months for the 5.4 mg/kg and 6.4 mg/kg dosages, respectively. Grade ≥3 drug-related treatment-emergent adverse events were seen in 38.6% and 58.0% of pts on the respective dosages, with ILD/pneumonitis occurring in 12.9% and 28.0% of the pts.
Both dosages of T-DXd (5.4 mg/kg and 6.4 mg/kg) maintained strong and durable responses and had an overall acceptable and manageable safety profile for pretreated HER2m mNSCLC pts. The 5.4 mg/kg dosage exhibited a better safety profile with a lower occurrence of ILD/pneumonitis than the 6.4 mg/kg dosage.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/1001
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04644237
Janne, P., Goto, Y., Kubo, T., Ninomiya, K., Kim, S-W., Planchard, D., Ahn, M-J., Smit, E.F., Langen, A.J.D., Pérol, M., Pons-Tostivint, E., Novello, S., Hayashi, H., Shimizu, J., Kim, D-W., Pereira, K., Cheng, F-C., Taguchi, A., Cheng, Y., Goto, K. Trastuzumab Deruxtecan in Patients with HER2-Mutant Metastatic Non-Small Cell Lung Cancer: Primary Results of DESTINY-Lung02.
