Phase II Study of Nivolumab Plus Ipilimumab with Platinum-Based Chemotherapy for Treatment-Naïve Advanced Non-Small Cell Lung Cancer with Untreated Brain Metastases: NIke Trial (LOGiK2004)

Abstract

The standard of care for advanced non-small cell lung cancer (NSCLC) without known driver oncogenes is immune checkpoint inhibitor (ICI) therapy combined with platinum-based chemotherapy. About 20% of patients with advanced NSCLC have brain metastases, which are related to poor prognosis. However, the effect of ICI therapy combined with platinum-based chemotherapy on untreated brain metastases derived from NSCLC remains unclear. The primary endpoint of this study is intracranial response rate as determined by modified Response Evaluation Criteria in Solid Tumors (RECIST) for brain metastases of ≥5 mm as target lesions. Eligible patients are 20 years of age or older with chemotherapy-naïve advanced NSCLC and at least one brain metastasis ≥5 mm in size that has not been previously treated. Patients receive nivolumab plus ipilimumab intravenously combined with histology-based platinum doublet chemotherapy (two cycles). Individuals with known genetic driver alterations such as those affecting EGFR or ALK are excluded. Planned enrollment is 30 patients over 2.5 years at 27 oncology facilities in Japan. This is the first prospective study to focus on the intracranial response to ICI therapy combined with platinum-based chemotherapy in patients with untreated brain metastases derived from NSCLC. If the study demonstrates intracranial efficacy for this patient population, then this regimen has the potential to become a new treatment option for such individuals.

Keywords:

• clinical trial
• NSCLC
• nivolumab plus ipilimumab
• brain metastases
• intracranial response rate

Acknowledgments

We thank the patients, their families, and all of the investigators who participate in the study (Supplementary table). This study is a collaboration of the Lung Oncology Group in Kyushu (LOGiK). Data management and monitoring for the study are conducted by Clinical Research Support Center Kyushu under a funding contract with Ono Pharmaceutical Co. Ltd. and Bristol-Myers Squibb K.K.

Disclosure

Dr.Tsuchiya-Kawano has received personal fees from Taiho Pharmaceutical, Chugai Pharma, Ono Pharmaceutical and Kyowa Kirin, all outside the submitted work. Dr.Shiraishi has received honoraria and research grants from Chugai Pharma as well as honoraria from Eli Lilly and Co., Ono Pharmaceutical, AstraZeneca, and Taiho Pharmaceutical, all outside the submitted work. Dr.Okamoto has received research grants and personal fees from AstraZeneca, Taiho Pharmaceutical, Chugai Pharma, Boehringer-Ingelheim, Ono Pharmaceutical, MSD Oncology, Eli Lilly and Co., and Bristol-Myers Squibb; research grants from Astellas Pharma, Novartis, and AbbVie; and personal fees from Pfizer, all outside the submitted work. The authors report no other conflicts of interest in this work.