A Study of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC

Non-Small-Cell Lung Carcinoma Clinical Trial

— ARTEMIDE-01  

Official title:

Phase I/II, Open-label, Dose Escalation and Dose Expansion Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC

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
• 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
• 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Non-Small-Cell Lung Carcinoma

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.