Phase II Study of Rilvegostomig and Ramucirumab in Combination Therapy for the Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer

The primary objectives of this study are to evaluate the safety and tolerability of novel agent combinations, establish the recommended dose, and determine the antitumour activity by measuring the objective response rate in participants with locally advanced or metastatic non-small cell lung cancer.

The secondary objectives include:

• Further evaluation of efficacy through tumour response and overall survival.
• Assessment of the pharmacokinetic profile of the study interventions.
• Evaluation of the immunogenicity of the study interventions.

This clinical trial involves a total of 174 participants diagnosed with non-small cell lung cancer. The study population includes both male and female patients. The age range corresponds to specific coded categories provided by the sponsor. Eligible participants must have a WHO/ECOG performance status of 0 or 1 and a life expectancy of at least 12 weeks. Inclusion requires the presence of at least one lesion qualifying as a RECIST 1.1 Target Lesion at baseline, alongside adequate bone marrow and organ function. For specific sub-studies, participants must have histologically or cytologically documented advanced or metastatic disease with PD-L1 tumor cell expression levels meeting defined thresholds. Furthermore, the absence of sensitizing EGFR mutations or ALK rearrangements is required, along with no other known actionable genomic alterations. The primary objectives of the study are:

• To assess the safety and tolerability and determine the recommended dose of the combination of novel anti-cancer agents.
• To assess the efficacy of novel agents in combination with other anti-cancer agents by evaluation of objective response rate.

This Phase II, open-label, multi-drug, multi-centre study is designed to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and antitumour activity of novel combinations in participants with non-small cell lung cancer. The research methodology focuses on assessing the objective response rate and determining recommended doses for combinations involving rilvegostomig and ramucirumab, potentially in conjunction with auxiliary agents such as mycophenolate mofetil and infliximab. The primary endpoints include the frequency of adverse events and serious adverse events. Secondary endpoints consist of best overall response, change in target lesion size, progression-free survival, disease control rate at 12 weeks, duration of response, overall survival, serum concentration, maximum plasma drug concentration, and immunogenicity. The study is expected to conclude by April 2029.

Rilvegostomig is an investigational medicinal product administered as a solution for infusion via intravenous infusion at a dose of 999 mg.

Ramucirumab is an investigational medicinal product administered via intravenous infusion at a dose of 10 mg/kg.

Mycophenolate mofetil is utilized as an auxiliary treatment and is administered via the oral route at a dose of 3 g.

Infliximab is utilized as an auxiliary treatment and is administered via intravenous infusion at a dose of 5 mg/kg for participants with non-small cell lung cancer.

Efficacy in participants with non-small cell lung cancer is evaluated through several clinical endpoints. The primary efficacy endpoint is the objective response rate (ORR). Secondary efficacy assessments include the best overall response (BOR), progression-free survival (PFS), overall survival (OS), and the duration of response (DoR).

Additional efficacy and pharmacological parameters involve the following:

• Change in target lesion tumor size.
• Disease control rate (DCR) at 12 weeks.
• Serum concentration and maximum plasma drug concentration (Cmax).
• Immunogenicity of the study interventions.