A Platform Study in Non-Small Cell Lung Cancer (NSCLC)
- Conditions
- Advanced or Metastatic Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT06996782
- Lead Sponsor
- AstraZeneca
- Brief Summary
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.
- Detailed Description
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 sub-studies (sub-study 1 and sub-study 2) and each sub-study focused on a specific treatment 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.
Sub-study 1 will investigate the safety, tolerability, and anti-tumour activity of combination of rilvegostomig and AB248.
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 182
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Sub study 2 Part A: Safety run-in Cisplatin Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen. Sub study 2 Part A: Safety run-in Carboplatin Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen. Sub study 2 Part A: Safety run-in Pemetrexed Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen. Sub study 2 Part A: Safety run-in Paclitaxel Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen. Sub study 2 Part A: Safety run-in Nab-paclitaxel Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen. Sub study 2 Part A: Safety run-in Ramucirumab Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen. Sub study 2 Part B: Dose expansion Rilvegostomig Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. Sub study 2 Part B: Dose expansion Cisplatin Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. Sub study 2 Part B: Dose expansion Carboplatin Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. Sub study 2 Part B: Dose expansion Pemetrexed Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. Sub study 2 Part B: Dose expansion Paclitaxel Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. Sub study 2 Part B: Dose expansion Nab-paclitaxel Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. Sub study 2 Part B: Dose expansion Ramucirumab Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts. Sub study 1 Part A: Safety run-in Rilvegostomig Participants will receive AB248 in combination with rilvegostomig to identify the RP2D to futher evaluate the combination in Part B. Sub study 1 Part A: Safety run-in AB248 Participants will receive AB248 in combination with rilvegostomig to identify the RP2D to futher evaluate the combination in Part B. Sub study 1 Part B: Dose expansion Rilvegostomig Participants with squamous and non-squamous NSCLC (programmed death-ligand 1 \[PD-L1\] ≥ 50% and PD-L1 1-49%) will receive AB248 in combination with rilvegostomig based on the RP2D determined in Part A. Sub study 1 Part B: Dose expansion AB248 Participants with squamous and non-squamous NSCLC (programmed death-ligand 1 \[PD-L1\] ≥ 50% and PD-L1 1-49%) will receive AB248 in combination with rilvegostomig based on the RP2D determined in Part A. Sub study 2 Part A: Safety run-in Rilvegostomig Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen.
- Primary Outcome Measures
Name Time Method Part A and Part B: Number of participants with adverse events (AEs) and serious adverse events (SAEs) Approximately 46 months To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
Part A: Number of partcipants with dose limiting toxicity (DLT) Approximately 46 months To assess the safety and tolerability and determine RP2D of the combination of novel anti-cancer agents.
Part B: Objective response (OR) Approximately 46 months The OR is defined as a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR).
- Secondary Outcome Measures
Name Time Method Part A: Objective response (OR) Approximately 46 months The OR is defined as a BOR of confirmed CR or confirmed PR.
Part A and Part B: Duration of response (DOR) Approximately 46 months 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).
Part A and Part B: Time to response (TTR) Approximately 46 months Time to response is defined as the time from the start of treatment until the date of first documented response.
Part A and Part B: Disease control (DC) Approximately 46 months 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.
Part A and Part B: Progression free survival (PFS) Approximately 46 months 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.
Part A and Part B: Progression free survival at 6 months (PFS6) From Day 1 pre-dose to 6 months 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.
Part A and Part B: Progression free survival at 12 months (PFS12) From Day 1 pre-dose to 12 months 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.
Part A and Part B: Overall survival (OS) Approximately 46 months 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.
Part A and Part B: Overall survival at 12 months (OS12) From Day 1 pre-dose to 12 months 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.
Part A and Part B: Serum concentration Approximately 46 months To assess the serum concentration of the novel anti-cancer agents in combination.
Part A and Part B: Maximum plasma drug concentration (Cmax) Approximately 46 months To assess the Cmax of the novel anti-cancer agents in combination.
Part A and Part B: Area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast) Approximately 46 months To assess the AUClast of the novel anti-cancer agents in combination.
Part A and Part B: Area under plasma concentration-time curve from time 0 to infinity (AUC∞) Approximately 46 months To assess the AUC∞ of the novel anti-cancer agents in combination.
Part A and Part B: Time to reach maximum concentration following drug administration (tmax) Approximately 46 months To assess the tmax of the novel anti-cancer agents in combination.
Part A and Part B: Terminal elimination half-life (t1/2λz) Approximately 46 months To assess the t1/2λz of the novel anti-cancer agents in combination.
Part A and Part B: Clearance (CL) Approximately 46 months To assess the CL of the novel anti-cancer agents in combination.
Part A and Part B: Volume of distribution at terminal phase (Vz) Approximately 46 months To assess the Vz of the novel anti-cancer agents in combination.
Part A and Part B: Number of participants with anti-drug antibodies (ADAs) Approximately 46 months To assess the immunogenicity of the novel anti-cancer agents in combination.
Trial Locations
- Locations (1)
Research Site
🇹🇷Ankara, Turkey
Research Site🇹🇷Ankara, Turkey