An Open-Label, Multi-Drug, Multi-Centre, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumour Activity of Novel Combinations in Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (LIBRA)
Summary
This is a Phase II, multi-center, open-label platform study evaluating novel combination treatment options in participants with locally advanced or metastatic NSCLC. The study will consist of several sub-studies, each evaluating the safety, tolerability, and preliminary antitumour activity of various treatment combinations. This study will be conducted in approximately 80 centers globally across 10 countries.
Detailed description
The master protocol will include 3 sub-studies, each focused on a specific disease population. * Sub-study 1 will investigate rilvegostomig± ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 ≥50%. * Sub-study 2 will investigate rilvegostomig + ramucirumab in 1L non-actionable genomic alterations (AGA) NSCLC with PD-L1 1-49%. * Sub-study 3 will investigate Dato-DXd + ramucirumab ± rilvegostomig in 2/3L AGA+ Each sub-study may include 2 parts (unless stated in the individual sub study protocols): Part A: one or more Safety Run-in cohort(s), and Part B: one or more Dose Expansion cohort(s).
Arms & interventions
- DrugRilvegostomig
Rilvegostomig will be administered as IV infusion.
- DrugRamucirumab
Ramucirumab will be administered as IV infusion.
- DrugDato-DXd
Dato-DXd will be administered as IV infusion.
Outcome measures
Primary
Number of participants with adverse events (AE) and serious adverse events (SAE)
To assess the safety and tolerability
Time frame: Through study completion, an average of 3 years
Objective response rate (ORR)
ORR is defined as the proportion of participants who have a confirmed CR (complete response) or confirmed PR (partial response) per RECIST 1.1
Time frame: Through study completion, an average of 3 years
Secondary
Best Overall Response(BOR)
Time frame: Through study completion, an average of 3 years
Change in Target Lesion Tumor Size
Time frame: Through study completion, an average of 3 years
Progression free survival (PFS)
Time frame: Through study completion, an average of 3 years
Disease Control Rate(DCR) at 12 Weeks
Time frame: From Day 1 pre-dose to 12 weeks
Duration Of Response (DoR)
Time frame: Through study completion, an average of 3 years
Overall Survival(OS)
Time frame: Through study completion, an average of 3 years
Serum concentration
Time frame: Through study completion, an average of 3 years
Maximum plasma drug concentration (Cmax)
Time frame: Through study completion, an average of 3 years
Immunogenicity of study interventions in participants receiving treatment
Time frame: Through study completion, an average of 3 years
Eligibility criteria
Study locations (6)
Research Site
Santa Monica, California, 90404
Research Site
Santa Rosa, California, 95403
Research Site
Atlanta, Georgia, 30318
Research Site
Baltimore, Maryland, 21231
Research Site
Houston, Texas, 77090
Research Site
Fairfax, Virginia, 22031