A Study of AZD2936 Anti-TIGIT/Anti-PD-1 Bispecific Antibody in Participants With Advanced or Metastatic NSCLC (ARTEMIDE-01)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small-Cell Lung Carcinoma
• Intervention / Treatment: Drug: AZD2936

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).

• Study Type: Interventional
• Enrollment (Actual): 212
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne, Australia, 3000
    • Research Site
• Belgium
  • Anderlecht, Belgium, 1070
    • Research Site
  • Leuven, Belgium, 3000
    • Research Site
• Brazil
  • Florianópolis, Brazil, 88034-000
    • Research Site
  • Natal, Brazil, 59075-740
    • Research Site
  • Porto Alegre, Brazil, 90035903
    • Research Site
  • Rio de Janeiro, Brazil, 20231-050
    • Research Site
  • São Paulo, Brazil, 01246-000
    • Research Site
• China
  • Chengdu, China, 610041
    • Research Site
  • Chongqing, China, 400030
    • Research Site
• Denmark
  • Copenhagen, Denmark, 2100
    • Research Site
• France
  • Dijon, France, 21079
    • Research Site
  • Toulouse, France, 31059
    • Research Site
• Georgia
  • Tbilisi, Georgia, 0112
    • Research Site
• Japan
  • Kashiwa, Japan, 227-8577
    • Research Site
  • Niigata, Japan, 951-8566
    • Research Site
  • Sendai, Japan, 981-0914
    • Research Site
  • Tokyo, Japan, 104-0045
    • Research Site
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • Research Site
  • Kuching, Malaysia, 93586
    • Research Site
• Moldova
  • Chisinau, Moldova, MD-2025
    • Research Site
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Research Site
  • Leiden, Netherlands, 2333 ZA
    • Research Site
  • Utrecht, Netherlands, 3584 CX
    • Research Site
• South Korea
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 05505
    • Research Site
  • Seoul, South Korea, 03082
    • Research Site
• Spain
  • Barcelona, Spain, 08035
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Madrid, Spain, 28027
    • Research Site
• Taiwan
  • Taichung, Taiwan
    • Research Site
  • Taichung, Taiwan, 40201
    • Research Site
  • Tainan, Taiwan, 70403
    • Research Site
  • Taipei, Taiwan, 110
    • Research Site
• Thailand
  • Bangkok, Thailand, 10700
    • Research Site
  • Chanthaburi, Thailand, 22000
    • Research Site
  • Muang, Thailand, 50200
    • Research Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Site
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 130 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced Non-small Cell Lung Cancer (NSCLC); Rilvegostomig Intravenous (IV) monotherapy	Drug: AZD2936; Anti-TIGIT/Anti-PD-1 Bispecific Antibody; Other Names: Rilvegostomig
Experimental: Dose Expansion Part B: CPI experienced NSCLC; Rilvegostomig IV monotherapy	Drug: AZD2936; Anti-TIGIT/Anti-PD-1 Bispecific Antibody; Other Names: Rilvegostomig
Experimental: Dose Expansion Part C: CPI Naive NSCLC; Rilvegostomig IV monotherapy	Drug: AZD2936; Anti-TIGIT/Anti-PD-1 Bispecific Antibody; Other Names: Rilvegostomig
Experimental: Dose Expansion Part D: CPI Naive NSCLC; Rilvegostomig IV monotherapy	Drug: AZD2936; Anti-TIGIT/Anti-PD-1 Bispecific Antibody; Other Names: Rilvegostomig
Experimental: Dose Expansion Part E: treatment Naive Squamous NSCLC; Rilvegostomig IV monotherapy	Drug: AZD2936; Anti-TIGIT/Anti-PD-1 Bispecific Antibody; Other Names: Rilvegostomig

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, 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	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	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)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).
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.
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, 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).
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, 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	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	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).
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, D and E.
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, 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.	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	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	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.

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2021
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 16, 2021
• First Submitted That Met QC Criteria: July 29, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 20, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• 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
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body
• Other Study ID Numbers: D7020C00001; 2021-000857-23 (EudraCT Number); 2023-508262-15-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level datain an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No