KEY TAKEAWAYS
- The phase I/II trial assessed the safety and effectiveness of inetetamab combined with pyrotinib for treating advanced NSCLC with HER2 mutation pts.
- The primary endpoint was to determine the DLT dosage and safety. Secondary endpoints included ORR, DCR, PFS, and OS.
- The study found early data from inetetamab + pyrotinib for advanced NSCLC with HER2 mutations showed manageable safety and promising antitumor activity.
Currently, there are few targeted therapies for HER2-mutant NSCLC. Pyrotinib has shown antitumor activity, but the combination of Inetetamab + Pyrotinib safety and efficacy are unknown.
Researchers aimed to assess the safety and effectiveness of inetetamab in combination with pyrotinib for treating advanced NSCLC with HER2 mutation patients(pts).
The study involved HER2 mutant pts with advanced lung cancer; they examined the combination of inetetamab and pyrotinib. The study had two phases: dose escalation and dose expansion. They used a “3+3” design during dose escalation to determine the drug’s dose-limiting toxicity(DLT). Inetetamab was given every 3 weeks (8 mg/kg for the first cycle, then 6 mg/kg for subsequent cycles) along with pyrotinib (doses varied). The primary endpoint was to determine DLT and safety, assessed during a 21-day evaluation period after the first dose. Secondary endpoints included assessing response rates, disease control, progression-free survival (PFS), and overall survival(OS).
The study with 8 enrolled pts, no DLTs occurred during the escalation period of pyrotinib at 240mg and 320mg. Pyrotinib at 320mg was chosen for further expansion. The most common treatment-related adverse events (TRAEs) were diarrhea (66.7% [2/3] in pyrotinib 240mg group, 95.6% [43/45] in pyrotinib 320mg group), rash (66.7% [2/3] in pyrotinib 240mg group, 22.2% [10/45] in pyrotinib 320mg group), and vomiting (0 in pyrotinib 240mg group, 24.4% [11/45] in pyrotinib 320mg group), mostly of Grade 1-2. About 7 pts experienced Grade 3 TRAEs (1 in pyrotinib 240mg group, 6 in pyrotinib 320mg group). Preliminary efficacy results showed an objective response rate (ORR) of 0% and a disease control rate (DCR) of 66.7% for the inetetamab with pyrotinib 240mg group. In comparison, the inetetamab with pyrotinib 320mg group had an ORR of 36.6% and a DCR of 85.4%. Further updates on the relationship between different mutation subtypes or co-mutations and efficacy will be provided during conference reports.
The study found early data from inetetamab + pyrotinib for advanced NSCLC with HER2 mutations showed manageable safety and promising antitumor activity.
Source: https://ascopubs.org/doi/abs/10.1200/JCO.2023.41.16_suppl.9105#:~:text=
Clinical Trial: https://www.clinicaltrials.gov/study/NCT05016544
Wenfeng Fang, Yuanyuan Zhao, Yan Huang, Yaxiong Zhang, Shaodong Hong, Yihua Huang, Hongyun Zhao, Yunpeng Yang, Shen Zhao, Gang Chen, Huaqiang Zhou, Yuxiang Ma, Ningning Zhou, and Li Zhang. DOI: 10.1200/JCO.2023.41.16_suppl.9105 Journal of Clinical Oncology 41, no. 16_suppl (June 01, 2023) 9105-9105.
