A multinational pivotal study of sunvozertinib in platinum pretreated non-small cell lung cancer with EGFR exon 20 insertion mutations: Primary analysis of WU-KONG1 study.

James Chih-Hsin Yang National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan info_outline James Chih-Hsin Yang, Ludovic Doucet, Mengzhao Wang, Yun Fan, Meili Sun, Laurent Greillier, David Planchard, Julien Mazieres, Enriqueta Felip, Bruna Pellini, Joaquim Bosch-Barrera, Manuel Cobo, Alessandra Bearz, Luis G. Paz-Ares, Lyudmila Bazhenova, Elaine Shum, Marcello Tiseo, Hector Soto Parra, Li Zheng, Pasi A. Janne

Authors James Chih-Hsin Yang National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan info_outline James Chih-Hsin Yang, Ludovic Doucet, Mengzhao Wang, Yun Fan, Meili Sun, Laurent Greillier, David Planchard, Julien Mazieres, Enriqueta Felip, Bruna Pellini, Joaquim Bosch-Barrera, Manuel Cobo, Alessandra Bearz, Luis G. Paz-Ares, Lyudmila Bazhenova, Elaine Shum, Marcello Tiseo, Hector Soto Parra, Li Zheng, Pasi A. Janne Organizations National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan, Institut de Cancérologie de l'Ouest, Saint-Herblain, France, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, Zhejiang Cancer Hospital, Hangzhou, China, Jinan Central Hospital, Jinan, China, Assistance Publique-Hôpitaux de Marseille (AP-HM), Aix Marseille University (AMU), Marseille, France, Institut Gustave Roussy, Department of Medical Oncology, Villejuif, France, Hôpital Larrey, CHU de Toulouse, Toulouse, France, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Catalan Institute of Oncology, Doctor Josep Trueta University Hospital, Girona, Spain, Hospital Universitario Regional Málaga, Málaga, Spain, Centro di Riferimento Oncologico di Aviano, Aviano, Italy, Medical Oncology Department, Hospital Universitario 12 de Octubre, Universidad Complutense de Madrid, Madrid, Spain, University of California, San Diego, Moores Cancer Center, San Diego, CA, Perlmutter Cancer Center, NYU Langone Health, New York, NY, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy, Azienda Ospedaliero Universitaria Policlinico G. Rodolico - San Marco, Catania, Italy, Dizal Pharmaceutical, Shanghai, China, Dana-Farber Cancer Institute, Boston, MA Abstract Disclosures Research Funding Dizal Pharmaceuticals Background: A multinational pivotal study WU-KONG1 (NCT03974022) has been conducted to assess sunvozertinib (DZD9008) in pre-treated non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations (exon20ins). Here we report the results of primary analysis. Methods: WU-KONG1 Part B is a phase 2, multinational pivotal study to assess the antitumor efficacy of sunvozertinib at two dose levels, 200 mg and 300 mg, in platinum pre-treated NSCLC patients with EGFR exon20ins. Eligible patients were randomized at the ratio of 1:1 to receive 200 mg or 300 mg sunvozertinib once daily until discontinuation criteria were met. Randomization was stratified by brain metastasis at baseline and number of regimens of prior systemic anti-cancer therapy. The primary endpoint was Independent Review Committee (IRC) assessed objective response rate (ORR) (per RECIST v1.1) and key secondary endpoint included IRC assessed duration of response (DoR). Results: As of January 4, 2024, a total of 184 patients were randomized to receive sunvozertinib treatment at 200 mg or 300 mg. Patients who met the predefined criteria for efficacy analysis were included in the primary analysis. The majority of patients (96.0%) had metastatic diseases, 60.7% had ECOG PS of 1, and 23.7% had baseline brain metastasis. All patients received prior platinum-based chemotherapy for advanced NSCLC, and 43.4% and 13.3% had prior onco-immunotherapy or amivantamab treatment. Per IRC assessment, the best ORR was 54.3% (41.0% confirmed and 5.8% pending confirmation). Confirmed complete response (CR) was achieved in 2.9% patients. The disease control rate (including CR, PR and stable disease) was 90.8%. The primary endpoint met its predefined target, with statistical significance. Tumor response was observed in patients with baseline brain metastasis, different demographics and EGFR exon20ins subtypes. With median follow-up time of 5.5 months for responders, the duration of response has not been reached, with 74.6% responders still responding. The PFS data are not mature with approximately 6-month follow-up. Safety findings were similar to previously reported results of sunvozertinib in other clinical studies. The most common drug-related TEAEs included diarrhea, skin rash and CPK increase. The majority of the TEAEs were CTCAE grade 1 or 2 and clinically manageable. Conclusions: In this primary analysis of WU-KONG1 multinational pivotal study, sunvozertinib demonstrated promising antitumor efficacy in platinum pre-treated NSCLC with EGFR exon20ins, with a tolerable safety profile. The updated data will be presented at the meeting. Clinical trial information: NCT03974022.

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