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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT04995523
Other study ID # D7020C00001
Secondary ID 2021-000857-23
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date September 14, 2021
Est. completion date November 27, 2025

Study information

Verified date April 2024
Source AstraZeneca
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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-D (dose expansion).


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 179
Est. completion date November 27, 2025
Est. primary completion date November 27, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 130 Years
Eligibility 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. - 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. - 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. - Primary or secondary resistance after treatment with 2 or more regimens including a CPI. - Symptomatic central nervous system (CNS) metastasis. - Thromboembolic event within 3 months prior to enrolment. - Other invasive malignancy within 2 years prior to screening.

Study Design


Intervention

Drug:
AZD2936
Anti-TIGIT/Anti-PD-1 Bispecific Antibody

Locations

Country Name City State
Australia Research Site Melbourne
Belgium Research Site Anderlecht
Belgium Research Site Leuven
Brazil Research Site Florianópolis
Brazil Research Site Natal
Brazil Research Site Porto Alegre
Brazil Research Site Rio de Janeiro
Brazil Research Site Sao Paulo
China Research Site Chengdu
China Research Site Chongqing
Denmark Research Site Copenhagen
France Research Site Dijon
France Research Site Toulouse Cedex 09
Japan Research Site Kashiwa
Japan Research Site Niigata-shi
Japan Research Site Sendai-shi
Japan Research Site Tokyo
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Korea, Republic of Research Site Seoul
Malaysia Research Site Kuala Lumpur
Malaysia Research Site Kuching
Netherlands Research Site Groningen
Netherlands Research Site Leiden
Netherlands Research Site Utrecht
Spain Research Site Barcelona
Spain Research Site Madrid
Spain Research Site Madrid
Taiwan Research Site Taichung
Taiwan Research Site Taichung
Taiwan Research Site Tainan City
Taiwan Research Site Taipei City
Thailand Research Site Bangkok
Thailand Research Site Muang
Thailand Research Site Mueang Chanthaburi
United States Research Site Chicago Illinois
United States Research Site Fairfax Virginia
United States Research Site Rochester Minnesota

Sponsors (1)

Lead Sponsor Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  China,  Denmark,  France,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Spain,  Taiwan,  Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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. Part A, B, C and D: From the time of informed consent until 90 days after the last dose of rilvegostomig
Primary Rate of rilvegostomig discontinuation due to toxicity Percentage of participants with AEs leading to discontinuation of rilvegostomig Part A, B, C and D: From first dose to the last dose of rilvegostomig (an average of 6 months)
Primary Objective Response Rate (ORR) Percentage of participants with a confirmed Complete Response (CR) or Partial Response (PR) according to RECIST v1.1 Part B, C and D: From first dose of rilvegostomig to progressive disease (PD) or death in the absence of disease progression (approximately 2 years)
Secondary ORR Percentage of participants with a confirmed CR or PR according to RECIST v1.1 Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
Secondary 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 Part A, B, C: 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).
Secondary Duration of response (DoR) The time from first response according to RECIST v1.1 until progression or death in the absence of disease progression Part A, B, C and D: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
Secondary Durable response rate (DRR) The percentage of participants according to RECIST v1.1 with a confirmed CR or PR lasting 6 months or more Part A, B, C and D: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).
Secondary 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 Part B, C: 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).
Secondary Measure the receptor occupancy (RO) of TIGIT and PD-1 on peripheral blood Evaluation of the target engagement of rilvegostomig in 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.
Secondary PK of rilvegostomig: Maximum plasma concentration of the study drug (Cmax) Maximum observed plasma concentration of rilvegostomig 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 and D.
Secondary PK of rilvegostomig: Area under the concentration-time curve (AUC) Area under the plasma concentration-time curve 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 and D.
Secondary PK of rilvegostomig: Clearance A pharmacokinetic measurement of the volume of plasma from which the study intervention is completely removed per unit time. 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 and D.
Secondary PK of rilvegostomig: Terminal elimination half-life (t 1/2) Terminal elimination half life 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 and D.
Secondary Incidence of anti-drug antibodies (ADA) against rilvegostomig in serum Immunogenicity of rilvegostomig 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 and D.
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