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

NCT04995523 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: D7020C000012023-508262-15-002021-000857-23
• Study Type: interventional
• Target: 212
• Locations: 16 countries
• Sites: 40

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.

Conditions

Non-Small-Cell Lung Carcinoma

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

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (11)

• ORR

  Part A: From first dose of rilvegostomig to PD or death in the absence of disease progression (approximately 2 years).

• 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).

• 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).

• 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).

• 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).

Study Arms (5)

Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced Non-small Cell Lung Cancer (NSCLC)

EXPERIMENTAL

Rilvegostomig Intravenous (IV) monotherapy

Drug: AZD2936

Dose Expansion Part B: CPI experienced NSCLC

EXPERIMENTAL

Rilvegostomig IV monotherapy

Drug: AZD2936

Dose Expansion Part C: CPI Naive NSCLC

EXPERIMENTAL

Rilvegostomig IV monotherapy

Drug: AZD2936

Dose Expansion Part D: CPI Naive NSCLC

EXPERIMENTAL

Rilvegostomig IV monotherapy

Drug: AZD2936

Dose Expansion Part E: treatment Naive Squamous NSCLC

EXPERIMENTAL

Rilvegostomig IV monotherapy

Drug: AZD2936

Interventions

AZD2936 DRUG

Anti-TIGIT/Anti-PD-1 Bispecific Antibody

Also known as: Rilvegostomig

Dose Escalation Part A: Checkpoint inhibitor (CPI) experienced Non-small Cell Lung Cancer (NSCLC); Dose Expansion Part B: CPI experienced NSCLC; Dose Expansion Part C: CPI Naive NSCLC; Dose Expansion Part D: CPI Naive NSCLC; Dose Expansion Part E: treatment Naive Squamous NSCLC

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (40)

Research Site

Chicago, Illinois, 60637, United States

Location

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Rochester, Minnesota, 55905, United States

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Fairfax, Virginia, 22031, United States

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Melbourne, 3000, Australia

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Anderlecht, 1070, Belgium

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Leuven, 3000, Belgium

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Florianópolis, 88034-000, Brazil

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Natal, 59075-740, Brazil

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Porto Alegre, 90035903, Brazil

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Rio de Janeiro, 20231-050, Brazil

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São Paulo, 01246-000, Brazil

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Chengdu, 610041, China

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Chongqing, 400030, China

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Copenhagen, 2100, Denmark

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Dijon, 21079, France

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Toulouse, 31059, France

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Tbilisi, 0112, Georgia

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Kashiwa, 227-8577, Japan

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Niigata, 951-8566, Japan

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Sendai, 981-0914, Japan

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Tokyo, 104-0045, Japan

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Kuala Lumpur, 59100, Malaysia

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Kuching, 93586, Malaysia

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Chisinau, MD-2025, Moldova

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Groningen, 9713 GZ, Netherlands

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Leiden, 2333 ZA, Netherlands

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Utrecht, 3584 CX, Netherlands

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Seoul, 03082, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Barcelona, 08035, Spain

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Madrid, 28027, Spain

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Madrid, 28041, Spain

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Taichung, 40201, Taiwan

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Taichung, Taiwan

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Tainan, 70403, Taiwan

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Taipei, 110, Taiwan

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Bangkok, 10700, Thailand

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Chanthaburi, 22000, Thailand

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Muang, 50200, Thailand

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Parkinson Disease 4, Autosomal Dominant Lewy Body; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study includes 5 parts: Part A: Dose escalation; B \& C \& E: Dose expansion non-randomized; D: Randomized RP2D \& alternative dose.

Study Record Dates

• First Submitted: July 16, 2021
• First Posted: August 9, 2021
• Study Start: September 14, 2021
• Primary Completion (Estimated): August 28, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 24, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

FR (2); MY (2); GE (1); TW (4); US (3); MO (1); NL (3); DK (1); BE (2); ES (3); JP (4); KR (3); AU (1); BR (5); TH (3); CN (2)