Abstract CT009: SHR-A1811, a HER2-directed antibody-drug conjugate (ADC), in advanced <i>HER2</i>-mutant non-small cell lung cancer (NSCLC): Updated phase 2 results from HORIZON-Lung

Abstract Background: SHR-A1811 is a novel ADC consisting of a humanized HER2-directed monoclonal antibody, cleavable tetrapeptide-based linker, and DNA topoisomerase I inhibitor. We conducted a multicenter, open-label, phase 1/2 study to evaluate SHR-A1811 in HER2-altered NSCLC. In the registrational phase 2 portion in patients (pts) with HER2-mutant NSCLC, the primary endpoint of IRC-assessed ORR was met (DCO, Jun. 14, 2024). Here, we presented an updated analysis after an additional 6-mo follow-up, focusing on survival outcomes. Methods: Pts with advanced NSCLC and centrally confirmed HER2 mutation, previously treated with (or intolerance to) platinum-based chemo and anti-PD-1/PD-L1 therapy, were enrolled. SHR-A1811 was administered at 4.8 mg/kg IV Q3W. Results: 94 pts were enrolled and treated. Median prior lines of therapy was 2 (range 1-9); all received platinum-based chemo and anti-PD-1/PD-L1 therapy and 23.4% received anti-HER2 TKI. 25.5% had BM at baseline. The most common HER2 mutation was exon 20 insertions (overall, 94.7%; A775_G776insYVMA, 72.3%). As of DCO (Dec. 14, 2024), median follow-up was 14.2 mo (range 4.7-18.2). Per IRC, ORR was 74.5% (95% CI 64.4-82.9); median DoR was 9.8 mo (95% CI 8.3-13.9). Median PFS was 11.5 mo (95% CI 9.7-15.2), with consistent benefits observed across baseline subgroups (Table 1). Efficacy per INV is shown in Table 1. Median OS was not reached; 12-mo OS rate was 88.2% (95% CI 79.8-93.3). Grade ≥3 TRAEs occurred in 63 (67.0%) pts; all with incidence ≥5% were haematological toxicities. ILD occurred in 8 (8.5%; grade 1-2, n=7; grade 3, n=1) pts. TRAEs led to dose discontinuation in 2 (2.1%) pts. There was no treatment-related death. Conclusions: At the updated analysis, SHR-A1811 continued to show clinically meaningful efficacy with a manageable safety profile in pts with previously treated HER2-mutant NSCLC, supporting it as a potential new treatment option for this population. Citation Format: Shun Lu, Ziming Li, Yan Wang, Yuping Sun, Linlin Wang, Xingya Li, Longhua Sun, Zhiyi He, Haiyan Yang, Yongsheng Wang, Qiming Wang, Zhengbo Song, Wei Hong, Yong Wang, Guohao Xia, Yan Yu, Min Peng, Yong Song, Donglin Wang, Rui Meng, Jian Fang, Yongzhong Luo, Wenhua Liang, Sheng Hu, Zhihui Wang, Haichuan Su, Zhiyong He, Liuning Li, Wei Guo, Zhentian Liu, Qitao Yu, Yun Zhao, Runxiang Yang, Peng Chen, Yiru Wang, You Li, Lulu Yang, Wei Shi. SHR-A1811, a HER2-directed antibody-drug conjugate (ADC), in advanced HER2-mutant non-small cell lung cancer (NSCLC): Updated phase 2 results from HORIZON-Lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT009.

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Cancer Research
Published
2025-04-25
DOI
https://doi.org/10.1158/1538-7445.am2025-ct009
Primary Topic
HER2/EGFR in Cancer Research
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article
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article

Abstract CT009: SHR-A1811, a HER2-directed antibody-drug conjugate (ADC), in advanced HER2-mutant non-small cell lung cancer (NSCLC): Updated phase 2 results from HORIZON-Lung

Longhua Sun, Shun Lü, Guohao Xia, Donglin Wang et al.
Cancer Research
HER2/EGFR in Cancer Research
article

Abstract CT009: SHR-A1811, a HER2-directed antibody-drug conjugate (ADC), in advanced HER2-mutant non-small cell lung cancer (NSCLC): Updated phase 2 results from HORIZON-Lung

Longhua Sun, Shun Lü, Guohao Xia, Donglin Wang, Zhiyong He, Qitao Yu, Haichuan Su, Yongzhong Luo, Yiru Wang, Haiyan Yang, Wei Hong, Yun Fu Zhao, Zhengbo Song, Wei Shi, Sheng Hu, Liuning Li, Wei Guo, Jian Fang, Rui Meng, Linlin Wang, Yongsheng Wang, Peng Chen, You Li, Yan Yu, Qiming Wang, Yong Wang, Zhihui Wang, Yong Song, Zhiyi He, Wenhua Liang, Lulu Yang, Yuping Sun, Ziming Li, Runxiang Yang, Xingya Li, Zhentian Liu, Min Peng, Yan Wang
article en

Abstract

Abstract Background: SHR-A1811 is a novel ADC consisting of a humanized HER2-directed monoclonal antibody, cleavable tetrapeptide-based linker, and DNA topoisomerase I inhibitor. We conducted a multicenter, open-label, phase 1/2 study to evaluate SHR-A1811 in HER2-altered NSCLC. In the registrational phase 2 portion in patients (pts) with HER2-mutant NSCLC, the primary endpoint of IRC-assessed ORR was met (DCO, Jun. 14, 2024). Here, we presented an updated analysis after an additional 6-mo follow-up, focusing on survival outcomes. Methods: Pts with advanced NSCLC and centrally confirmed HER2 mutation, previously treated with (or intolerance to) platinum-based chemo and anti-PD-1/PD-L1 therapy, were enrolled. SHR-A1811 was administered at 4.8 mg/kg IV Q3W. Results: 94 pts were enrolled and treated. Median prior lines of therapy was 2 (range 1-9); all received platinum-based chemo and anti-PD-1/PD-L1 therapy and 23.4% received anti-HER2 TKI. 25.5% had BM at baseline. The most common HER2 mutation was exon 20 insertions (overall, 94.7%; A775_G776insYVMA, 72.3%). As of DCO (Dec. 14, 2024), median follow-up was 14.2 mo (range 4.7-18.2). Per IRC, ORR was 74.5% (95% CI 64.4-82.9); median DoR was 9.8 mo (95% CI 8.3-13.9). Median PFS was 11.5 mo (95% CI 9.7-15.2), with consistent benefits observed across baseline subgroups (Table 1). Efficacy per INV is shown in Table 1. Median OS was not reached; 12-mo OS rate was 88.2% (95% CI 79.8-93.3). Grade ≥3 TRAEs occurred in 63 (67.0%) pts; all with incidence ≥5% were haematological toxicities. ILD occurred in 8 (8.5%; grade 1-2, n=7; grade 3, n=1) pts. TRAEs led to dose discontinuation in 2 (2.1%) pts. There was no treatment-related death. Conclusions: At the updated analysis, SHR-A1811 continued to show clinically meaningful efficacy with a manageable safety profile in pts with previously treated HER2-mutant NSCLC, supporting it as a potential new treatment option for this population. Citation Format: Shun Lu, Ziming Li, Yan Wang, Yuping Sun, Linlin Wang, Xingya Li, Longhua Sun, Zhiyi He, Haiyan Yang, Yongsheng Wang, Qiming Wang, Zhengbo Song, Wei Hong, Yong Wang, Guohao Xia, Yan Yu, Min Peng, Yong Song, Donglin Wang, Rui Meng, Jian Fang, Yongzhong Luo, Wenhua Liang, Sheng Hu, Zhihui Wang, Haichuan Su, Zhiyong He, Liuning Li, Wei Guo, Zhentian Liu, Qitao Yu, Yun Zhao, Runxiang Yang, Peng Chen, Yiru Wang, You Li, Lulu Yang, Wei Shi. SHR-A1811, a HER2-directed antibody-drug conjugate (ADC), in advanced HER2-mutant non-small cell lung cancer (NSCLC): Updated phase 2 results from HORIZON-Lung [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT009.

Cancer ResearchVol. 85(8_Supplement_2)
Central South University (CN), Nanchang University (CN), Harbin Medical University (CN), Sun Yat-sen University (CN), Chongqing University (CN), Guangxi Medical University (CN), Shanghai Jiao Tong University (CN), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), Peking University (CN), Sichuan University (CN), Nanjing General Hospital of Nanjing Military Command (CN), Tianjin Medical University Cancer Institute and Hospital (CN), Shanghai Chest Hospital (CN), Wuhan University (CN), Zhengzhou University (CN), West China Hospital of Sichuan University (CN), Peking University Cancer Hospital (CN), Jiangxi Provincial Cancer Hospital (CN), First Affiliated Hospital of Guangzhou Medical University (CN), Zhejiang Cancer Hospital (CN), Shanxi Provincial Cancer Hospital (CN), Third Affiliated Hospital of Harbin Medical University (CN), Guangdong Provincial Hospital of Traditional Chinese Medicine (CN), Nanjing Drum Tower Hospital (CN), Fifth Affiliated Hospital of Sun Yat-sen University (CN), Hunan Cancer Hospital (CN), First Affiliated Hospital of GuangXi Medical University (CN), Jiangsu Cancer Hospital (CN), Anhui Provincial Hospital (CN), Renmin Hospital of Wuhan University (CN), Henan Cancer Hospital (CN), Chongqing Cancer Hospital (CN), First Affiliated Hospital of Zhengzhou University (CN), Hubei Cancer Hospital (CN), Shandong First Medical University (CN), Union Hospital (CN), First Affiliated Hospital of Nanchang University (CN), Hangzhou Cancer Hospital (CN), Huazhong University of Science and Technology (CN), Nanjing Medical University (CN), Guangzhou Medical University (CN)
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HER2/EGFR in Cancer Research
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