Hong et al. investigated sac-TMT, a TROP2-targeted antibody–drug conjugate, in combination with tagitanlimab (anti-PD-L1) as a first-line therapy in advanced NSCLC without actionable genomic alterations. In cohorts 1A (q3w, n=40) and 1B (q2w, n=63) in the open-label trial, ORRs were 40% and 66.7%, with mPFS of 15.4 months and Not Reached, respectively. Treatment response did not differ by baseline TROP2 or PD-L1 expression, nor by histological subtype. The most common Grade 3+ AEs were hematologic (neutropenia, lymphopenia, anemia). Serious TRAEs occurred in 10.0% and 20.6% of patients, but TRAE-related discontinuation was minimal, and no deaths occurred.
Contributed by Morgan Janes
ABSTRACT: Sacituzumab tirumotecan (sac-TMT, also known as MK-2870 or SKB264) is an antibody-drug conjugate targeting trophoblast cell surface antigen 2. We report the initial findings from the ongoing phase 2 OptiTROP-Lung01 study, evaluating the combination of sac-TMT and tagitanlimab (KL-A167), an anti-PD-L1 antibody, as first-line therapy in patients with advanced or metastatic non-small-cell lung cancer who lack actionable genomic alterations (cohorts 1A and 1B). Cohort 1A received sac-TMT (5_mg_kg(-1), every 3_weeks) plus tagitanlimab (1,200_mg, every 3_weeks) in each 3-week cycle, whereas cohort 1B was treated with sac-TMT (5_mg_kg(-1), every 2_weeks) plus tagitanlimab (900_mg, every 2 weeks) in each 4-week cycle, in a nonrandomized manner until disease progression or unacceptable toxicity. The primary endpoints included safety and objective response rate. This study was not powered for formal hypothesis testing. A total of 40 and 63 patients were enrolled in cohorts 1A and 1B, respectively. The median age was 63_years in both cohorts. An Eastern Cooperative Oncology Group performance status of 1 was observed in 97.5% and 85.7% of patients in cohorts 1A and 1B, respectively. In cohorts 1A and 1B, the most common grade ³3 treatment-related adverse events were decreased neutrophil count (30.0% and 34.9%), decreased white blood cell count (5.0% and 19.0%) and anemia (5.0% and 19.0%). No treatment-related deaths were observed. After median follow-ups of 19.3_months for cohort 1A and 13.0_months for cohort 1B, the confirmed objective response rate in the full analysis set was 40.0% (16 of 40) and 66.7% (42 of 63), the disease control rate was 85.0% and 92.1% and median progression-free survival was 15.4_months (95% confidence interval 6.7-17.9) and not reached for cohorts 1A and 1B, respectively. sac-TMT plus tagitanlimab showed promising efficacy as a first-line treatment for advanced or metastatic non-small-cell lung cancer, with a manageable safety profile. ClinicalTrials.gov registration: NCT05351788 .
Author Info: (1) Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, C
Author Info: (1) Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China. (2) The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China. Henan Cancer Hospital, Zhengzhou, China. Institute of Cancer Research, Henan Academy of Innovations in Medical Science, Zhengzhou, China. (3) Jilin Cancer Hospital, Changchun, China. (4) Hunan Cancer Hospital, Changsha, China. (5) The First Hospital of China Medical University, Shenyang, China. (6) Shanxi Cancer Hospital, Taiyuan, China. (7) West China Hospital of Sichuan University, Chengdu, China. (8) The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. (9) Hunan Cancer Hospital, Changsha, China. (10) Harbin Medical University Cancer Hospital, Harbin, China. (11) Hubei Cancer Hospital, Wuhan, China. (12) Chongqing University Cancer Hospital, Chongqing, China. (13) The Second Affiliated Hospital of Nanchang University, Nanchang, China. (14) Shandong Cancer Hospital, Jinan, China. (15) Zhejiang Cancer Hospital, Hangzhou, China. (16) The First Affiliated Hospital of Xiamen University, Xiamen, China. (17) Jiangsu Province Hospital, Nanjing, China. (18) Beijing Cancer Hospital, Beijing, China. (19) Sichuan Kelun-Biotech Biopharmaceutical Co Ltd, Chengdu, China. (20) Sichuan Kelun-Biotech Biopharmaceutical Co Ltd, Chengdu, China. (21) Sichuan Kelun-Biotech Biopharmaceutical Co Ltd, Chengdu, China. National Engineering Research Center of Targeted Biologics, Chengdu, China. (22) Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China. zhangli@sysucc.org.cn. (23) Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University, Guangzhou, China. fangwf@sysucc.org.cn.
