Non-Small-Cell Lung Carcinoma
Conditions
Keywords
TIGIT, Anti-TIGIT, PD-1, Anti-PD-1, NSCLC, Non-small Cell Lung Cancer, Advanced, Metastatic, Solid Tumor, Solid Tumour, Stage 3 NSCLC, Stage III NSCLC, Stage 4 NSCLC, Stage IV NSCLC, PD L1+ tumors
Brief summary
This is a Phase I/II study designed to evaluate if experimental anti-TIGIT/anti-PD-1 bispecific antibody rilvegostomig (AZD2936) is safe, tolerable and efficacious in participants with Advanced or Metastatic Non-small Cell Lung Cancer.
Detailed description
This is a first-time-in-human (FTIH), open-label, multicenter, multi-part, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of rilvegostomig (AZD2936) in adult participants with stage III unresectable or stage IV NSCLC. The study includes 4 parts: Part A (dose escalation) and Parts B-E (dose expansion).
Interventions
DRUGAZD2936
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The study includes 5 parts: Part A: Dose escalation; B & C & E: Dose expansion non-randomized; D: Randomized RP2D & alternative dose.
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Written informed consent * Aged 18 or above * Part A and Part B: Unresectable stage III or stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part C and Part D: Stage IV squamous or non-squamous NSCLC not amenable to curative surgery or radiation. Part E: Stage IV squamous NSCLC not amenable to curative surgery or radiation. * Documented PD-L1 expression by PD-L1 IHC per local report. * Part A and Part B: Confirmed progression during treatment with a CPI-including regimen. * Part C and Part D: No prior I/O treatment for metastatic NSCLC. * Part E: No prior treatment for metastatic NSCLC. * ECOG performance status of 0 or 1 at enrolment. * Life expectancy of ≥ 12 weeks at enrolment. * Have at least 1 measurable lesion per RECIST v1.1. * Adequate bone marrow, liver and kidney function
Exclusion criteria
* Sensitizing epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) fusion * Documented test result for any other known genomic alteration for which a targeted therapy is approved in first line per local standard of care (e.g. ROS1, NTRK fusions, BRAF, V600E mutation) * Previous treatment with an anti-TIGIT therapy * Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment. * Part A and Part B: Primary or secondary resistance after treatment with 2 or more regiments including a CPI. * Part C and Part D: Any prior systemic treatment with an immune oncology agent (prior administration of immune-oncology agent for curative intent to treat other invasive malignancy is permitted). Treatment with one previous systemic chemotherapy will be allowed. * Part E: Any prior systemic treatment for metastatic NSCLC, including but not limited to chemotherapy, anti-PD-1, anti-PD-L1, anti-CTLA-4. * Symptomatic central nervous system (CNS) metastasis. * Thromboembolic event within 3 months prior to enrolment. * Other invasive malignancy within 2 years prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with adverse events (AEs) and immune mediated AEs (imAEs), serious AEs (SAEs), dose limiting toxicities (DLTs), vital signs, and abnormal laboratory parameters | Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig | A DLT is a toxicity defined by the study protocol that occurs from the first dose of study intervention up to the end of the DLT evaluation period that is assessed as clearly unrelated to the primary disease or intercurrent illness. |
| Rate of rilvegostomig discontinuation due to toxicity | Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months) | Percentage of participants with AEs leading to discontinuation of rilvegostomig |
| Objective Response Rate (ORR) | Part B, C, D and E: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years) | Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). | Percentage of participants with a confirmed CR or PR according to RECIST v1.1 |
| Disease control rate (DCR) | Part A, B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years). | Percentage of participants who have a best objective response of confirmed CR or PR or who have SD lasting for at least a certain time of period after start of treatment |
| Duration of response (DoR) | Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). | The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression |
| Durable response rate (DRR) | Part A, B, C, D and E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). | The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more |
| Progression-free survival (PFS) | Part B, C, E: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years). Part D: From randomization to PD or death in the absence of disease progression (approximately 2 years). | The time from first dose of study intervention until the date of objective disease progression or death in the absence of disease progression |
| Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood | Part A, B: From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B. | Evaluation of the target engagement of rilvegostomig in peripheral blood |
| PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax) | From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E. | Maximum observed plasma concentration of rilvegostomig |
| PK of rilvegostomig: Area under the concentration-time curve (AUC) | From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E. | Area under the plasma concentration-time curve |
| PK of rilvegostomig: Clearance | From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E. | A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time. |
| PK of rilvegostomig: Terminal elimination half-life (t 1/2) | From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E. | Terminal elimination half life |
| Incidence of anti-drug antibodies (ADA) against rilvegostomig in serum | From first dose of study intervention, at predefined intervals throughout the administration of rilvegostomig (approximately 2 years). The predefined intervals for Part A will be different from Part B, C, D and E. | Immunogenicity of rilvegostomig |
Countries
Australia, Belgium, Brazil, China, Denmark, France, Georgia, Japan, Malaysia, Moldova, Netherlands, South Korea, Spain, Taiwan, Thailand, United States
Outcome results
None listed