Abstract CT032: Promotive clinical effects of pembrolizumab with necitumumab in patients having advanced non-small cell lung cancer with PD-L1 expression of 50% or higher in a phase II study (K-TAIL-202)

Abstract Background: Pembrolizumab is the standard of care for advanced non-small cell lung cancer (NSCLC) with high programmed death-1 ligand 1 (PD-L1) expression. However, combination therapies comprising pembrolizumab and ipilimumab, tiragolumab, or lenvatinib have not demonstrated superior efficacy in this patient group. This study explored the effectiveness of the novel combination of pembrolizumab and necitumumab as first-line therapy in patients having advanced NSCLC with PD-L1 expression of 50% or higher. Methods: Patients with untreated advanced NSCLC with PD-L1 expression of 50% or higher received pembrolizumab and necitumumab every 3 weeks up to 35 cycles. The primary endpoint was investigator-assessed objective response rate (ORR), and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. The sample size was calculated using 80% power with a one-sided alpha error of 10%, a threshold ORR of 39. 0%, and an expected ORR of 54. 8%. Results: From December 2020 to March 2023, 50 patients were enrolled. Patient characteristics were as follows: male/female patients: 38/12; median age: 72 years (range: 51-90 years) ; histology, adenocarcinoma/squamous cell carcinoma/other: 35/15/5; and PS, 0/1: 20/30. At the time of the primary analysis, the ORR was 76. 0% (95% CI: 61. 9%-86. 9%), with 2. 0%, 74. 0%, 10. 0%, and 8. 0% of the patients showing complete response, partial response, stable disease, and progressive disease, respectively. The median PFS was 15. 7 months (95% CI, 10. 3 to not reached) and the median OS was not reached. Common toxicities included rash (86%) and hypomagnesemia (60%). Grade 3 interstitial lung disease was noted in 5 patients (10%) and grade 5 cardiac arrest in 1 patient (2%). Conclusion: Combination therapy comprising pembrolizumab and necitumumab demonstrated a 76. 0% ORR, meeting the primary endpoint, with manageable toxicities. The regimen showed promising clinical activity in patients with NSCLC and high PD-L1 expression, warranting further investigation. Clinical trial ID: jRCT2031200248. Citation Format: Atsushi Horiike, Hiroshi Wakui, Shunichi Sugawara, Yuji Minegishi, Sadatomo Tasaka, Sojiro Kusumoto, Toshio Sakatani, Hiroyuki Suzuki, Yukio Hosomi, Yuichi Tambo, Tsuneo Shimokawa, Hiroo Ishida, Eisaku Miyauchi, Katsuhiko Naoki, Tatsuro Fukuhara, Emiko Mura, Toshiaki Tsurui, Risako Suzuki, Nana Iriguchi, Tomoyuki Ishiguro, Yuya Hirasawa, Ryo Manabe, Masahiro Shimokawa, Ryotaro Ohkuma, Hirotsugu Ariizumi, Yutaro Kubota, Kazuyuki Hamada, Sachiko Takenoshita, Kakei Ryu, Takehiko Sambe, Eisuke Inoue, Satoshi Wada, Kiyoshi Yoshimura, Hironori Sagara, Shinichi Kobayashi, Takuya Tsunoda. Promotive clinical effects of pembrolizumab with necitumumab in patients having advanced non-small cell lung cancer with PD-L1 expression of 50% or higher in a phase II study (K-TAIL-202) abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT032.