The purpose of this study is to assess the safety and efficacy of multiple study interventions including novel-novel combinations or novel agents in combination with standard therapy for the treatment of metastatic NSCLC.
This is a multicentre, open-label study to evaluate the safety and efficacy of various combinations of study interventions in participants with advanced or metastatic NSCLC (mNSCLC). The study will include a sub-study (sub-study 2) focused on a specific treatment that may include 2 parts - 1. Part A consisting of one of more safety run-in cohorts to evaluate 2 or more dose levels to identify the recommended Phase 2 dose (RP2D) unless RP2D has been established then Part A will not be required; and 2. Part B consisting of one or more expansion cohorts. The originally planned Sub-study 1 was withdrawn (cancelled) and will not be conducted. Sub-study 2 will evaluate the safety, tolerability, and anti-tumour activity of rilvegostomig plus standard of care (SoC) platinum-based chemotherapy, with or without ramucirumab.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
152
Rilvegostomig will be administered as an intravenous (IV) infusion.
Cisplatin will be administered as SoC as an IV infusion.
Carboplatin will be administered as SoC as an IV infusion.
Part A and Part B: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
Time frame: Approximately 46 months
Part A: Number of partcipants with dose limiting toxicity (DLT)
To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
Time frame: Approximately 46 months
Part B: Objective response (OR)
The OR is defined as a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR).
Time frame: Approximately 46 months
Part A: Objective response (OR)
The OR is defined as a BOR of confirmed CR or confirmed PR.
Time frame: Approximately 46 months
Part A and Part B: Duration of response (DOR)
The DoR is defined as the time from the date of first documented objective response (which is subsequently confirmed) until date of first documented disease progression or death (by any cause in the absence of disease progression).
Time frame: Approximately 46 months
Part A and Part B: Time to response (TTR)
Time to response is defined as the time from the start of treatment until the date of first documented response.
Time frame: Approximately 46 months
Part A and Part B: Disease control (DC)
Disease control is defined as if a participant has a best overall response of confirmed CR or confirmed PR or who have stable disease (SD) for at least 7 weeks after start of treatment.
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Pemetrexed will be administered as SoC as an IV infusion.
Paclitaxel will be administered as SoC as an IV infusion.
Nab-paclitaxel will be administered as SoC as an IV infusion.
Ramucirumab will be administered as an IV infusion.
Research Site
Phoenix, Arizona, United States
RECRUITINGResearch Site
Santa Rosa, California, United States
RECRUITINGResearch Site
Jacksonville, Florida, United States
RECRUITINGResearch Site
Baltimore, Maryland, United States
NOT_YET_RECRUITINGResearch Site
Detroit, Michigan, United States
NOT_YET_RECRUITINGResearch Site
Rochester, Minnesota, United States
RECRUITINGResearch Site
Cleveland, Ohio, United States
RECRUITINGResearch Site
Providence, Rhode Island, United States
NOT_YET_RECRUITINGResearch Site
Providence, Rhode Island, United States
NOT_YET_RECRUITINGResearch Site
Tyler, Texas, United States
RECRUITING...and 94 more locations
Time frame: Approximately 46 months
Part A and Part B: Progression free survival (PFS)
Progression-free survival is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from assigned therapy or receives another anti-cancer therapy prior to progression.
Time frame: Approximately 46 months
Part A and Part B: Progression free survival at 6 months (PFS6)
Progression-free survival is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from assigned therapy or receives another anti-cancer therapy prior to progression.
Time frame: From Day 1 pre-dose to 6 months
Part A and Part B: Progression free survival at 12 months (PFS12)
Progression-free survival is defined as the time from the start of treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the participant withdraws from assigned therapy or receives another anti-cancer therapy prior to progression.
Time frame: From Day 1 pre-dose to 12 months
Part A and Part B: Overall survival (OS)
Overall survival is defined as the time from the start of treatment until death due to any cause regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy.
Time frame: Approximately 46 months
Part A and Part B: Overall survival at 12 months (OS12)
Overall survival is defined as the time from the start of treatment until death due to any cause regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy.
Time frame: From Day 1 pre-dose to 12 months
Part A and Part B: Serum concentration
To assess the serum concentration of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Maximum plasma drug concentration (Cmax)
To assess the Cmax of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast)
To assess the AUClast of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Area under plasma concentration-time curve from time 0 to infinity (AUC∞)
To assess the AUC∞ of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Time to reach maximum concentration following drug administration (tmax)
To assess the tmax of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Terminal elimination half-life (t1/2λz)
To assess the t1/2λz of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Clearance (CL)
To assess the CL of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Volume of distribution at terminal phase (Vz)
To assess the Vz of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months
Part A and Part B: Number of participants with anti-drug antibodies (ADAs)
To assess the immunogenicity of the novel anti-cancer agents in combination.
Time frame: Approximately 46 months