Efficacy and safety of selpercatinib in Chinese patients with advanced RET fusion-positive non-small-cell lung cancer: a phase II clinical trial (LIBRETTO-321)

Shun Lu; Ying Cheng; Dingzhi Huang; Yuping Sun; Lin Wu; Chengzhi Zhou; Ye Guo; Jingxin Shao; Wanli Zhang; Jianying Zhou

doi:10.1177/17588359221105020

Efficacy and safety of selpercatinib in Chinese patients with advanced RET fusion-positive non-small-cell lung cancer: a phase II clinical trial (LIBRETTO-321)

Ther Adv Med Oncol. 2022 Jul 28:14:17588359221105020. doi: 10.1177/17588359221105020. eCollection 2022.

Authors

Shun Lu¹, Ying Cheng², Dingzhi Huang³, Yuping Sun⁴, Lin Wu⁵, Chengzhi Zhou⁶, Ye Guo⁷, Jingxin Shao⁸, Wanli Zhang⁸, Jianying Zhou⁹

Affiliations

¹ Department of Oncology, Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai JiaoTong University, Shanghai, China.
² Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, Jilin, 130012, China.
³ Department of Thoracic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
⁴ Department of Oncology, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
⁵ Department II of Thoracic Medicine, Hunan Cancer Hospital, Changsha, China.
⁶ Respiratory Medicine Department, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
⁷ Department of Medical Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.
⁸ Oncology, Eli Lilly and Company, Shanghai, China.
⁹ Department of Respiratory Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

Abstract

Introduction: Oncogenic alterations in RET occur in 1-2% of non-small-cell lung cancers (NSCLCs). The efficacy and safety of the first-in-class, highly selective, and potent RET inhibitor selpercatinib in Chinese patients with RET fusion-positive NSCLC remains unknown.

Methods: In this open-label, multicenter, phase II study (NCT04280081), patients with advanced RET-altered solid tumors received selpercatinib (160 mg orally twice daily) in a 28-day cycle. The primary endpoint was independent review committee (IRC)-assessed objective response rate (ORR; Response Evaluation Criteria in Solid Tumors v1.1). Secondary endpoints included duration of response, central nervous system (CNS) response, and safety. Efficacy against NSCLC was assessed in the primary analysis set (PAS; centrally confirmed RET status) and in all enrolled patients with NSCLC.

Results: Of 77 enrolled patients, 47 had RET fusion-positive NSCLC. After 9.7 months of median follow-up, IRC-assessed ORR in the PAS (n = 26) was 69.2% [95% confidence interval (CI), 48.2-85.7] and 94.4% of responses were ongoing; the ORR was 87.5% and 61.1% in treatment-naïve and pre-treated patients, respectively. IRC-assessed ORR in all patients with NSCLC (n = 47) was 66.0% (95% CI, 50.7-79.1). Among five patients with measurable CNS metastases at baseline, four (80%) achieved an IRC-assessed intracranial response. In the safety population (n = 77), most treatment-emergent adverse events (TEAEs) were grade 1 or 2. The most common grade ⩾3 TEAE was hypertension (19.5%). Three (3.9%) patients discontinued therapy due to treatment-related AEs; no deaths occurred due to treatment-related AEs.

Conclusion: Selpercatinib, with potent and durable antitumor activity including intracranial activity, was well tolerated in Chinese patients with RET fusion-positive NSCLC, consistent with LIBRETTO-001 (ClinicalTrials.gov: NCT04280081).

Keywords: Chinese; RET fusion; non-small-cell lung cancer; selective RET inhibitor; selpercatinib.

Associated data

ClinicalTrials.gov/NCT04280081