Abstract CT248: Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2 mutant non-small cell lung cancer (NSCLC): primary analysis from the Phase 2 DESTINY-Lung05 (DL-05) trial

Abstract Background: In China, non-approved therapies are used for pts with HER2 (ERBB2) mutant (HER2m) NSCLC. In DESTINY-Lung02 (DL-02), T-DXd 5. 4 mg/kg showed clinical benefit with an acceptable and manageable safety profile in pts with pretreated HER2m metastatic NSCLC. DL-02 did not include any Chinese pts. We report the primary analysis of T-DXd in Chinese pts with pretreated HER2m metastatic NSCLC. Methods: In this open-label, single-arm, Phase 2 trial (NCT05246514), Chinese pts with HER2m (locally or centrally confirmed activating HER2 exon 19 or 20 mutation) metastatic non-squamous NSCLC with disease progression on or after ≥1 prior anticancer therapy (no prior HER2-directed) received T-DXd 5. 4 mg/kg IV once every 3 weeks. The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR). Secondary endpoints included investigator-assessed (INV) confirmed ORR; ICR and INV duration of response, disease control rate, progression-free survival, and safety. Results: At data cutoff (September 23, 2023), 72 pts with HER2m NSCLC received T-DXd 5. 4 mg/kg (full analysis set). Median T-DXd exposure was 7. 9 (0. 7-13. 5) months. Pt characteristics and efficacy data are in the table. 71 pts had drug-related adverse events (AEs), of which 51. 4% were grade (G) ≥3. Most common G≥3 AEs by grouped term: neutropenia (26. 4%), thrombocytopenia (18. 1%), and leukopenia (11. 1%). Drug-related AEs leading to discontinuations occurred in 2 (2. 8%) pts. 17 (23. 6%) pts had serious AEs, with no INV-adjudicated G5. Centrally adjudicated drug-related ILD/pneumonitis occurred in 7 (9. 7%) pts (n=6 G2; n=1 G5). Conclusion: T-DXd 5. 4 mg/kg demonstrated clinically meaningful and durable responses and a manageable safety profile in Chinese pts with HER2m metastatic NSCLC. Results were consistent with DL-02 and the known safety profile of T-DXd, supporting its use in this pt population. TABLE 1. NAND Pt characteristics and efficacy data Full analysis set* N=72 Median age, years (min, max) 57. 0 (34, 76) Female, n (%) 41 (56. 9) Former smoker, n (%) 22 (30. 6) Prior lines of therapy, n (%) 1 30 (41. 7) ≥2 42 (58. 3) Most common prior treatment modalities, n (%) Cytotoxic chemotherapy 67 (93. 1) Platinum chemotherapy 65 (90. 3) Immunotherapy 49 (68. 1) Antiangiogenic therapy 49 (68. 1) Median duration of follow up, months (range) 9. 8 (1. 0–14. 0) Efficacy ICR INV Confirmed ORR, % (95% CI) 58. 3 (46. 1, 69. 8) 58. 3 (46. 1, 69. 8) Median DOR, months (95% CI) NE (6. 1, NE) 9. 0 (7. 2, NE) DCR, % (95% CI) 91. 7 (82. 7, 96. 9) 93. 1 (84. 5, 97. 7) Median PFS, months (95% CI) NE (7. 2, NE) 10. 8 (7. 2, NE) 12-month PFS rate, % (95% CI) 55. 1 (41. 4, 66. 8) 39. 7 (19. 5, 59. 4) *Pts with HERm assessed by central testing. CI, confidence interval; DCR, disease control rate; DOR, duration of response; HER2m, HER2 mutant; ICR, independent central review; INV, investigator assessed; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; pts, patients Citation Format: Ying Cheng, Lin Wu, Yong Fang, Yun Fan, Xingya Li, Mingjun Zhang, Yan Yu, Yu Yao, Ruilian Xu, Jun Guo, Huaping Yang, Jian Fang, Feng Luo, Xuhong Min, Ke-jing Tang, Jie Hu, Yunru Chen, Rui Mao, Victor Zhang, Dairong Li. Trastuzumab deruxtecan (T-DXd) in Chinese patients (pts) with previously treated HER2 mutant non-small cell lung cancer (NSCLC): primary analysis from the Phase 2 DESTINY-Lung05 (DL-05) trial abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT248.