Tambotatug Pelitecan in Small-Cell Lung Cancer after Platinum-Based Therapy

Author(s): Yuanyuan Zhao, M.D.¹; Hongxu Liu, M.D.²; Xiangjiao Meng, M.D.³; Zhihua Liu, M.D.⁴; Yan Yu, Ph.D.⁵; Yulong Zheng, Ph.D.⁶; Longhua Sun, M.D.⁷; Runxiang Yang, M.D.⁸; Jian Liu, M.M.⁹; Yanqiu Zhao, M.M.¹⁰; Lin Wu, Ph.D.¹¹; Lei Yang, M.D.¹²; Zhiye Zhang, M.D.¹³; Mingjun Li, M.D.¹⁴; Peng Zhang, M.D.¹⁵; Yan Zhang, Ph.D.¹⁶; Hua Zhong, M.D.¹⁷; Jiuwei Cui, M.D.¹⁸; Zhangzhou Huang, B.M.¹⁹; Yanwei Yin, M.M.²⁰; Manxiang Li, M.D.²¹; Fan Tong, Ph.D.²²; Dan Xue, M.M.²³; Dongqing Lv, M.M.²⁴; Xufeng Li, M.D.²⁵; Xian Zhang, Ph.D.²⁵; Steve Chin, M.D.²⁵; Jiaqiang Cai, Ph.D.²⁵; Tongtong Xue, Ph.D.²⁵; Yan Huang, M.D.¹; Hongyun Zhao, M.D.²⁶; Li Zhang, M.D.¹; the TAISHAN-302 Investigators*;

Source: DOI: 10.1056/NEJMoa2610229

Dr. Anjan Patel's Thoughts

This looks like a real second-line win in relapsed small-cell lung cancer (SCLC): the B7-H3 ADC tambotatug pelitecan beat topotecan on every endpoint, with median overall survival (OS) of 13 vs 9 mos, median progression-free survival (PFS) of 7 vs 3 mos, and a 59% vs 10% response rate, plus a 32% vs 3% intracranial response rate. It was also easier to tolerate than topotecan, with grade 3 or higher events in 55% vs 78%, though the 5% rate of ILD/pneumonitis (mostly low grade) means we'll need the usual ADC vigilance. The caveats are that this is an interim, open-label analysis with only about 9 mos of follow-up in an all-Chinese population, and the OS sits right next to tarlatamab's 14 mos in DeLLphi-304, so the next debate will be about sequencing these two.

BACKGROUND

Tambotatug pelitecan (known as Tam-Peli, a new antibody–drug conjugate that targets the immune-checkpoint molecule B7-H3) showed promising clinical efficacy in patients with relapsed extensive-stage small-cell lung cancer in early-phase trials.

METHODS

In this phase 3, multicenter, open-label, randomized trial, we assigned eligible patients with small-cell lung cancer that had progressed after first-line platinum-based therapy in a 1:1 ratio to receive tambotatug pelitecan or topotecan. The primary end point was overall survival. The key secondary end points were progression-free survival and objective response as assessed by investigators. Here, we report the results from the prespecified interim analysis. Research Summary Tambotatug Pelitecan in SCLC after Platinum-Based Therapy

RESULTS

A total of 451 patients underwent randomization: 225 were assigned to receive tambotatug pelitecan and 226 to receive topotecan. Overall survival was significantly longer with tambotatug pelitecan than with topotecan — a median of 13.3 months (95% confidence interval [CI], 12.1 to could not be estimated), as compared with 9.4 months (95% CI, 7.7 to 10.5); the stratified hazard ratio for death was 0.46 (95% CI, 0.35 to 0.62; P

CONCLUSIONS

Among patients with relapsed small-cell lung cancer after platinum-based therapy, treatment with tambotatug pelitecan resulted in longer overall survival, longer progression-free survival, and a higher percentage of patients with an objective response than treatment with topotecan, with a lower incidence of adverse events of grade 3 or higher. (Funded by the Innovative Drug Research and Development National Science and Technology Major Project and MediLink Therapeutics; TAISHAN-302 ClinicalTrials.gov number, NCT06612151.) Quick Take Tambotatug Pelitecan in Small-Cell Lung Cancer 2m 47s

Author Affiliations

¹Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou; ²Department of Thoracic Surgery, Cancer Hospital of Dalian University of Technology, Liaoning Cancer Hospital and Institute, Shenyang, China; ³Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Jinan, China; ⁴Department of Radiation Oncology, Jiangxi Cancer Hospital, Nanchang, China; ⁵Department of Thoracic Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China; ⁶Department of Medical Oncology, First Affiliated Hospital, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Zhejiang University School of Medicine, Hangzhou, China; ⁷Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Nanchang University, Nanchang, China; ⁸Second Department of Medical Oncology, Third Affiliated Hospital of Kunming Medical University, Yunnan Tumor Hospital, Kunming, China; ⁹Department of Clinical Pharmacy, First Affiliated Hospital, Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Zhejiang University School of Medicine, Hangzhou, China; ¹⁰Department of Oncology, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China; ¹¹Department of Thoracic Medical Oncology, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China; ¹²Department of Respiratory Oncology, Gansu Provincial Cancer Hospital, Lanzhou, China; ¹³Department of Oncology, First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China; ¹⁴Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; ¹⁵Department of Thoracic Surgery, Shanghai Pulmonary Hospital Affiliated to Tongji University, Shanghai; ¹⁶Lung Cancer Center, West China Hospital, Sichuan University, Chengdu; ¹⁷Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai; ¹⁸Department of Oncology, First Hospital of Jilin University, Changchun, China; ¹⁹Department of Thoracic Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China; ²⁰Oncology Day Treatment Center, Linyi People’s Hospital, Linyi, China; ²¹Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China; ²²Department of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; ²³Department of Pulmonary and Critical Care Medicine, Fujian Medical University Union Hospital, Fuzhou, China; ²⁴Department of Respiratory and Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, China; ²⁵MediLink Therapeutics, Suzhou, China; ²⁶Department of Clinical Research, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou

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