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.
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
212
Anti-TIGIT/Anti-PD-1 Bispecific Antibody
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
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.
Time frame: Part A, B, C, D and E: From the time of informed consent until 90 days after the last dose of rilvegostomig
Rate of rilvegostomig discontinuation due to toxicity
Percentage of participants with AEs leading to discontinuation of rilvegostomig
Time frame: Part A, B, C, D and E: From first dose to the last dose of rilvegostomig (an average of 6 months)
Objective Response Rate (ORR)
Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1
Time frame: 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)
ORR
Percentage of participants with a confirmed CR or PR according to RECIST v1.1
Time frame: Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
Disease control rate (DCR)
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
Time frame: 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).
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Research Site
Chicago, Illinois, United States
Research Site
Rochester, Minnesota, United States
Research Site
Fairfax, Virginia, United States
Research Site
Melbourne, Australia
Research Site
Anderlecht, Belgium
Research Site
Leuven, Belgium
Research Site
Florianópolis, Brazil
Research Site
Natal, Brazil
Research Site
Porto Alegre, Brazil
Research Site
Rio de Janeiro, Brazil
...and 30 more locations
Duration of response (DoR)
The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression
Time frame: 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).
Durable response rate (DRR)
The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more
Time frame: 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).
Progression-free survival (PFS)
The time from first dose of study intervention until the date of objective disease progression or death in the absence of disease progression
Time frame: 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).
Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood
Evaluation of the target engagement of rilvegostomig in peripheral blood
Time frame: 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.
PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax)
Maximum observed plasma concentration of rilvegostomig
Time frame: 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.
PK of rilvegostomig: Area under the concentration-time curve (AUC)
Area under the plasma concentration-time curve
Time frame: 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.
PK of rilvegostomig: Clearance
A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time.
Time frame: 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.
PK of rilvegostomig: Terminal elimination half-life (t 1/2)
Terminal elimination half life
Time frame: 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.
Incidence of anti-drug antibodies (ADA) against rilvegostomig in serum
Immunogenicity of rilvegostomig
Time frame: 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.