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

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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(7_Suppl):Abstract nr CT248.