A Study of Novel Combinations in Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT07098338
- Lead Sponsor
- AstraZeneca
- Brief 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 2L 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).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 278
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Sub-study 1, investigate rilvegostomig± ramucirumab in 1L non-AGA NSCLC with PD-L1 ≥50% Rilvegostomig Participants will receive rilvegostomig ± ramucirumab until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion Sub-study 1, investigate rilvegostomig± ramucirumab in 1L non-AGA NSCLC with PD-L1 ≥50% Ramucirumab Participants will receive rilvegostomig ± ramucirumab until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion Sub-study 2, investigate rilvegostomig + ramucirumab in 1L non-AGA NSCLC with PD-L1 1-49% Ramucirumab Participants will receive rilvegostomig + ramucirumab until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2L AGA+ NSCLC Ramucirumab Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion Sub-study 2, investigate rilvegostomig + ramucirumab in 1L non-AGA NSCLC with PD-L1 1-49% Rilvegostomig Participants will receive rilvegostomig + ramucirumab until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2L AGA+ NSCLC Rilvegostomig Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion Sub-study 3, investigate Dato-DXd + ramucirumab ± rilvegostomig in 2L AGA+ NSCLC Dato-DXd Participants will receive Dato-DXd + ramucirumab ± rilvegostomig until RECIST 1.1-defined radiological progression as assessed by the investigator, unacceptable toxicity, withdrawal of consent, or other discontinuation criterion
- Primary Outcome Measures
Name Time Method Number of participants with adverse events (AE) and serious adverse events (SAE) Through study completion, an average of 3 years To assess the safety and tolerability
Objective response rate (ORR) Through study completion, an average of 3 years ORR is defined as the proportion of participants who have a confirmed CR (complete response) or confirmed PR (partial response), determined by the Investigator at local site per RECIST 1.1
- Secondary Outcome Measures
Name Time Method Best Overall Response(BOR) Through study completion, an average of 3 years BOR is the best response a participant has had following randomisation/start of dosing, but prior to starting any subsequent cancer therapy and up to and including RECIST progression or the last evaluable assessment in the absence of RECIST progression
Change in Target Lesion Tumor Size Through study completion, an average of 3 years The best percentage change from baseline in Target Lesion tumour size is the largest decrease (or smallest increase) from baseline for a participant, using RECIST 1.1 assessments
Progression free survival (PFS) Through study completion, an average of 3 years PFS 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) per RECIST 1.1 as assessed by Investigator.
Disease Control Rate(DCR) at 12 Weeks From Day 1 pre-dose to 12 weeks DCR at 12 weeks is defined as the percentage of participants who have a best objective response of confirmed CR or PR or who have SD for at least 11 weeks after start of treatment (to allow for an early assessment within the assessment window).
Duration Of Response (DoR) Through study completion, an average of 3 years 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).
Overall Survival(OS) Through study completion, an average of 3 years OS is defined as the time from the start of treatment until death due to any cause.
Serum concentration Through study completion, an average of 3 years To assess the serum concentration of the novel anti-cancer agents in combination.
Maximum plasma drug concentration (Cmax) Through study completion, an average of 3 years To assess the Cmax of the novel anti-cancer agents in combination.
Immunogenicity of study interventions in participants receiving treatment Through study completion, an average of 3 years Presence of Anti Drug Antibodies（ADAs) for study interventions in serum/plasma
Trial Locations
- Locations (1)
Research Site
🇹🇭Banphaeo, Thailand
Research Site🇹🇭Banphaeo, Thailand