Non-squamous Non-small Cell Lung Cancer
Conditions
Keywords
ARTEMIDE-Lung03, Rilvegostomig (AZD2936), Non-squamous non-small cell lung cancer (NSCLC), Bi-specific antibody, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT), EGFR, ALK and ROS1 testing, Programmed cell death protein (PD-L1), Pembrolizumab, Carboplatin, Cisplatin, Pemetrexed
Brief summary
The purpose of ARTEMIDE-Lung03 is to evaluate the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a first-line treatment of patients with locally advanced or metastatic non-squamous NSCLC whose tumors express PD-L1.
Detailed description
This is a Phase III, two-arm, randomized, double-blind, global, multicenter study assessing the efficacy and safety of rilvegostomig compared to pembrolizumab, both in combination with platinum-based doublet chemotherapy, as a 1L treatment for patients with locally advanced or metastatic non-squamous NSCLC whose tumors express PD-L1 (TC ≥ 1%).
Interventions
DRUGRilvegostomig
Administered as one intravenously (IV) on Day 1 of each 21-day cycle
DRUGPembrolizumab
Administered as one intravenously (IV) on Day 1 of each 21-day cycle
DRUGCarboplatin
Administered as one intravenously (IV) on Day 1 of each 21-day cycle up to 4 cycles
DRUGCisplatin
Administered as one intravenously (IV) on Day 1 of each 21-day cycle up to 4 cycles
DRUGPemetrexed
Administered as one intravenously (IV) on Day 1 of each 21-day cycle
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind masking
Intervention model description
Arm A: Rilvegostomig in combination with platinum-based doublet chemotherapy followed by rilvegostomig monotherapy plus pemetrexed in maintenance. Arm B: Pembrolizumab in combination with platinum-based doublet chemotherapy followed by pembrolizumab monotherapy plus pemetrexed in maintenance.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically documented non-squamous NSCLC. * Stage III B/C or IV NSCLC (based on the American Joint Committee on Cancer Edition 8) not amenable to curative treatment. * Absence of sensitizing EGFR mutations (including, but not limited to, exon 19 deletion and exon 21 L858R, exon 21 L861Q, exon 18 G719X, and exon 20 S768I mutations) and ALK and ROS1 rearrangements. * Absence of documented tumor genomic mutation results from tests conducted as part of standard local practice in any other actionable driver oncogenes for which there are locally approved and available targeted 1L therapies. * Provision of acceptable tumor sample, to confirm tumor PD-L1 expression TC ≥ 1%. * At least one lesion not previously irradiated that qualifies as a RECIST 1.1 TL at baseline and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15 mm) with CT or MRI and is suitable for accurate repeated measurements. * Adequate organ and bone marrow function
Exclusion criteria
* Presence of small cell and neuroendocrine histology components. * Brain metastases unless asymptomatic, stable, and not requiring steroids or anticonvulsants for at least 7 days prior to randomization. A minimum of 2 weeks must have elapsed between the end of local therapy (brain radiotherapy or surgery) and randomization. Participants must have recovered from the acute toxic effect of radiotherapy (eg, dizziness and signs of increased intracranial pressure) or surgery prior to randomization. * Any prior systemic therapy received for NSCLC except in the neoadjuvant or adjuvant setting or definitive chemoradiotherapy with the intent to cure, provided that progression has occurred \> 12 months after the end of systemic therapy treatment. * Any prior exposure to an anti-TIGIT therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms. * Any prior treatment with an anti-PD-1 or anti-PD-L1 agent. * 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 and of low potential risk for recurrence. * Active or prior documented autoimmune or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs. * Active primary immunodeficiency/active infectious disease(s). * Active tuberculosis infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Up to approximately 6 years | OS is defined as the time from randomization until the date of death due to any cause. |
| Progression-free survival (PFS) | Up to approximately 6 years | PFS is defined as the time from randomization until radiological progression per RECIST 1.1, or death due to any cause (in the absence of progression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Landmark overall survival (OS) rates | Up to approximately 6 years | OS is defined as the time from randomization until the date of death due to any cause. |
| Landmark progression-free survival (PFS) rates | Up to approximately 6 years | PFS is defined as the time from randomization until radiological progression per RECIST 1.1, or death due to any cause (in the absence of progression). |
| Time to second progression or death (PFS2) | Up to approximately 6 years | PFS2 is defined as the time from randomization until the earliest of the progression event (following the initial progression event), after the start of the first subsequent therapy, or death from any cause, whichever occurs first. The date of the second progression will be recorded by the investigator in the eCRF and defined according to local standard clinical practice. |
| Overall response rate (ORR) | Up to approximately 6 years | ORR is defined as the proportion of participants who have a confirmed CR or confirmed PR, using RECIST 1.1. |
| Duration of response (DoR) | Up to approximately 6 years | DoR is defined as the time from the date of first documented response until the date of documented progression using RECIST 1.1 or death due to any cause (in the absence of progression). |
| Pharmacokinetic (PK) of rilvegostomig | Up to approximately 6 years | Concentration of rilvegostomig in serum |
| Immunogenicity of rilvegostomig | Up to approximately 6 years | Presence of antidrug antibodies (ADAs), titer, and neutralizing antibodies for rilvegostomig |
| Patient-reported global health status (GHS)/quality of life (QoL) | Up to approximately 6 years | TTD of GHS/QoL as measured by the EORTC IL172. TTD is defined as time from randomization to the date of first deterioration. Deterioration is defined as a worsening change from baseline that reaches a clinically meaningful change threshold. |
| Patient-reported physical functioning | Up to approximately 6 years | Proportion of participants with maintained or improved physical functioning as measured by PROMIS PF-SF 8c - 7 day at each time point. |
| Patient-reported lung cancer symptoms of non-small cell lung cancer (NSCLC) | Up to approximately 6 years | TTD in pulmonary symptoms as measured by the NSCLC-SAQ. TTD is defined as time from randomization to the date of first deterioration. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Italy, Japan, Malaysia, Netherlands, Peru, Poland, Puerto Rico, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States, Vietnam
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed