Non-Small Cell Lung Cancer
Conditions
Keywords
Non-Small Cell Lung Cancer(NSCLC), Antibody-Drug Conjugates (ADCs), T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) domains (TIGIT), Programmed death-ligand 1 (PD-L1)
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 2/3L 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).
Interventions
DRUGRilvegostomig
Rilvegostomig will be administered as IV infusion.
DRUGRamucirumab
Ramucirumab will be administered as IV infusion.
DRUGDato-DXd
Dato-DXd will be administered as IV infusion.
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
for All Sub-studies: * Participant must be ≥ 18 years of age at the time of signing the ICF * WHO/ECOG performance status of 0 or 1 * At least 1 lesion that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline. * Adequate bone marrow and organ function * Life expectancy ≥ 12 weeks * Provision of acceptable tumour tissue Specific Inclusion Criteria for Sub-Study 1 and Sub-Study 2: * Histologically or cytologically documented advanced or metastatic NSCLC * PD-L1 TC ≥ 1% (TC≥ 50% for sub-study 1, 1-49% for sub-study 2) * Absence of sensitizing EGFR mutations or ALK rearrangements. No known other Actionable Genomic Alterations(AGAs) Specific Inclusion Criteria for Sub-Study 3: * Histologically or cytologically documented advanced or metastatic non-squamous NSCLC * Documented positive AGA and had progressed on prior targeted therapy
Exclusion criteria
for All Sub-studies: * As judged by the investigator, any severe or uncontrolled systemic diseases, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardise compliance with the protocol * Active or prior documented autoimmune or inflammatory disorders * Persistent toxicities (CTCAE Grade ≥ 2) (NCI CTCAE v5.0) caused by previous anti cancer therapy, excluding alopecia. * Spinal cord compression or leptomeningeal carcinomatosis for sub-study 1 and sub-study 2. Unstable spinal cord compression for sub-study 3 * Unstable brain metastases * History of another primary malignancy. * Active infection, including TB and infections with HIV, HBV (verified by known positive HBsAg result), HCV. * Uncontrolled or significant cardiac disease * Receipt of prior systemic chemotherapy/chemoradiation/immunotherapy for advanced NSCLC for sub-study 1 and sub-study 2. * Prior exposure to immune-mediated therapy * History of uncontrolled hypertension, and active bleeding diseases, and high risks of bleeding and disorders of coagulation * Any concurrent anti-cancer treatment. * Receipt of live, attenuated vaccine within 30 days prior to the first dose of study intervention.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) per RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
Countries
Australia, Canada, China, Japan, Singapore, South Korea, Taiwan, Thailand, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed