Advanced or Metastatic Non-small Cell Lung Cancer
Conditions
Keywords
Checkpoint inhibitor (CPI), Platinum-based chemotherapy, T-cell immunoreceptor with lg and Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) domains (TIGIT), Programmed death-ligand 1 (PD-L1)
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 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 The originally planned Sub-study 1 was withdrawn (cancelled) and will not be conducted.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.
Interventions
DRUGRilvegostomig
Rilvegostomig will be administered as an intravenous (IV) infusion.
DRUGCisplatin
Cisplatin will be administered as SoC as an IV infusion.
DRUGCarboplatin
Carboplatin will be administered as SoC as an IV infusion.
DRUGPemetrexed
Pemetrexed will be administered as SoC as an IV infusion.
DRUGPaclitaxel
Paclitaxel will be administered as SoC as an IV infusion.
DRUGNab-paclitaxel
Nab-paclitaxel will be administered as SoC as an IV infusion.
DRUGRamucirumab
Ramucirumab will be administered as an IV infusion.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with confirmed squamous or non-squamous NSCLC with a current Stage IV mNSCLC. * Provision of acceptable archival tumour tissue (or fresh tumour tissue biopsy if archival tumour tissue is not available and if clinically feasible) is mandatory at screening. * Measurable disease as defined by at least one lesion that can be accurately measured at baseline as ≥ 10 mm at the longest diameter. * Minimum life expectancy of 12 weeks in the opinion of the investigator. * Adequate organ and marrow function. * Contraceptive use by male or female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Adequate organ and marrow function. Inclusion Criteria for Sub Study 2: * Programmed death-ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 1% (per local report). * Adequate coagulation and urinalysis. * Minimum body weight of 30 kg.
Exclusion criteria
* Participants with epidermal growth factor receptor mutations, anaplastic lymphoma receptor fusions or any other known genomic alteration for which targeted therapy is approved in the first line per local standard of care. * Presence of small cell and neuroendocrine histology components. * Any severe or uncontrolled systemic diseases, including uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; interstitial lung disease/pneumonitis (of any grade); unstable and/or symptomatic venous thromboembolism, serious chronic gastrointestinal conditions associated with diarrhoea, active non-infectious skin disease or substance abuse. * Has had a prior stem cell, bone marrow, allogenic tissue, or solid organ transplant. * Has an active autoimmune disease that has required systemic treatment in the past 5 years. * History of clinically significant arrhythmia, cardiomyopathy of any aetiology or symptomatic congestive heart failure. * History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention or presence of small cell and neuroendocrine histology components. * Persistent toxicities (common terminology criteria for adverse events \[CTCAE\] ≥ Grade 2) caused by previous anti-cancer therapy, excluding alopecia. * Spinal cord compression or symptomatic brain metastases. * Treatment with any other anti-cancer agents or immunosuppressive medication. * Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium, Brazil, China, France, Georgia, Germany, Italy, Japan, Malaysia, Moldova, Netherlands, Peru, Poland, Serbia, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed