A Platform Study in Non-Small Cell Lung Cancer (NSCLC)

NCT ID: NCT06996782

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

152 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-11-24

Study Completion Date

2029-02-23

Brief Summary

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The purpose of this study is to assess the safety and efficacy of multiple study interventions including novel-novel combinations or novel agents in combination with standard therapy for the treatment of metastatic NSCLC.

Detailed Description

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This is a multicentre, open-label study to evaluate the safety and efficacy of various combinations of study interventions in participants with advanced or metastatic NSCLC (mNSCLC).

The study will include sub-studies (sub-study 1 and sub-study 2) and each sub-study focused on a specific treatment may include 2 parts -

1. Part A consisting of one of more safety run-in cohorts to evaluate 2 or more dose levels to identify the recommended Phase 2 dose (RP2D) unless RP2D has been established then Part A will not be required; and
2. Part B consisting of one or more expansion cohorts.

Sub-study 1 will investigate the safety, tolerability, and anti-tumour activity of combination of rilvegostomig and AB248.

Sub-study 2 will evaluate the safety, tolerability, and anti-tumour activity of rilvegostomig plus standard of care (SoC) platinum-based chemotherapy, with or without ramucirumab.

Conditions

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Advanced or Metastatic Non-small Cell Lung Cancer

Keywords

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Checkpoint inhibitor Platinum-based chemotherapy Interleukin-2 (IL-2) T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) domains (TIGIT) Programmed death-ligand 1 (PD-L1)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sub study 1 Part A: Safety run-in

Participants will receive AB248 in combination with rilvegostomig to identify the RP2D to futher evaluate the combination in Part B.

Group Type EXPERIMENTAL

Rilvegostomig

Intervention Type DRUG

Rilvegostomig will be administered as an intravenous (IV) infusion.

AB248

Intervention Type DRUG

AB248 will be administered via syringe or an IV bag.

Sub study 1 Part B: Dose expansion

Participants with squamous and non-squamous NSCLC (programmed death-ligand 1 \[PD-L1\] ≥ 50% and PD-L1 1-49%) will receive AB248 in combination with rilvegostomig based on the RP2D determined in Part A.

Group Type EXPERIMENTAL

Rilvegostomig

Intervention Type DRUG

Rilvegostomig will be administered as an intravenous (IV) infusion.

AB248

Intervention Type DRUG

AB248 will be administered via syringe or an IV bag.

Sub study 2 Part A: Safety run-in

Participants with squamous and non-squamous NSCLC will receive combination therapy of rilvegostomig, ramucirumab, and platinum-based chemotherapy to assess the safety and tolerability of this regimen.

Group Type EXPERIMENTAL

Rilvegostomig

Intervention Type DRUG

Rilvegostomig will be administered as an intravenous (IV) infusion.

Cisplatin

Intervention Type DRUG

Cisplatin will be administered as SoC as an IV infusion.

Carboplatin

Intervention Type DRUG

Carboplatin will be administered as SoC as an IV infusion.

Pemetrexed

Intervention Type DRUG

Pemetrexed will be administered as SoC as an IV infusion.

Paclitaxel

Intervention Type DRUG

Paclitaxel will be administered as SoC as an IV infusion.

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as SoC as an IV infusion.

Ramucirumab

Intervention Type DRUG

Ramucirumab will be administered as an IV infusion.

Sub study 2 Part B: Dose expansion

Participants will be randomised 1:1 into one of 2 treatment arms (rilvegostomig + chemotherapy + ramucirumab OR rilvegostomig + chemotherapy) in non-squamous histology cohorts and into a single arm (rilvegostomig + chemotherapy+ ramucirumab) in squamous histology cohorts.

Group Type EXPERIMENTAL

Rilvegostomig

Intervention Type DRUG

Rilvegostomig will be administered as an intravenous (IV) infusion.

Cisplatin

Intervention Type DRUG

Cisplatin will be administered as SoC as an IV infusion.

Carboplatin

Intervention Type DRUG

Carboplatin will be administered as SoC as an IV infusion.

Pemetrexed

Intervention Type DRUG

Pemetrexed will be administered as SoC as an IV infusion.

Paclitaxel

Intervention Type DRUG

Paclitaxel will be administered as SoC as an IV infusion.

Nab-paclitaxel

Intervention Type DRUG

Nab-paclitaxel will be administered as SoC as an IV infusion.

Ramucirumab

Intervention Type DRUG

Ramucirumab will be administered as an IV infusion.

Interventions

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Rilvegostomig

Rilvegostomig will be administered as an intravenous (IV) infusion.

Intervention Type DRUG

AB248

AB248 will be administered via syringe or an IV bag.

Intervention Type DRUG

Cisplatin

Cisplatin will be administered as SoC as an IV infusion.

Intervention Type DRUG

Carboplatin

Carboplatin will be administered as SoC as an IV infusion.

Intervention Type DRUG

Pemetrexed

Pemetrexed will be administered as SoC as an IV infusion.

Intervention Type DRUG

Paclitaxel

Paclitaxel will be administered as SoC as an IV infusion.

Intervention Type DRUG

Nab-paclitaxel

Nab-paclitaxel will be administered as SoC as an IV infusion.

Intervention Type DRUG

Ramucirumab

Ramucirumab will be administered as an IV infusion.

Intervention Type DRUG

Other Intervention Names

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AZD2936

Eligibility Criteria

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Inclusion Criteria

* Participants with confirmed squamous or non-squamous NSCLC with a current Stage IV mNSCLC.
* Provision of acceptable archival tumour tissue (or fresh tumour tissue biopsy if archival tumour tissue is not available and if clinically feasible) is mandatory at screening.
* Measurable disease as defined by at least one lesion that can be accurately measured at baseline as ≥ 10 mm at the longest diameter.
* Minimum life expectancy of 12 weeks in the opinion of the investigator.
* Adequate organ and marrow function.
* Contraceptive use by male or female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Adequate organ and marrow function and minimum body weight of 30 Kg.
* PD-L1 tumour proportion score (TPS) ≥ 1% (per local report).


\- Adequate coagulation and urinalysis.

Exclusion Criteria

* Participants with epidermal growth factor receptor mutations, anaplastic lymphoma receptor fusions or any other known genomic alteration for which targeted therapy is approved in the first line per local standard of care.
* Any severe or uncontrolled systemic diseases, including uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; serious chronic gastrointestinal conditions associated with diarrhoea, active non-infectious skin disease or substance abuse.
* Has had a prior stem cell, bone marrow, allogenic tissue, or solid organ transplant.
* Has an active autoimmune disease that has required systemic treatment in the past 2 years.
* History of clinically significant arrhythmia, cardiomyopathy of any aetiology or symptomatic congestive heart failure.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥ 2 years before the first dose of study intervention or presence of small cell and neuroendocrine histology components.
* Unresolved toxicities of Grade ≥ 2 from prior anti-cancer therapy, spinal cord compression or symptomatic brain metastases.
* Any prior systemic therapy received for advanced or mNSCLC or treatment with any other anti-cancer agents or immunosuppressive medication.
* Palliative radiotherapy with a limited field of radiation within 2 weeks or with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks, prior to the first dose of study intervention.
* Active tuberculosis infection.
* Any prior exposure to an anti-T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif (ITIM) domains (TIGIT) therapy or any other anticancer therapy targeting immune-regulatory receptors or mechanisms.
* Any prior systemic treatment with an immune-oncology agent, including but not limited to anti-PD-1, anti-PD-L1, anti-Cytotoxic T-lymphocyte Associated Antigen 4 (CTLA-4).


* Has a known history of human immunodeficiency virus (HIV) infection.
* Has either a known history of Hepatitis B virus (HBV) or has active Hepatitis C virus (HCV).
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis/interstitial lung disease.
* Any concomitant medication known to be associated with Torsades de pointes.


* Known active hepatitis A.
* Acute hepatitis B infection (anti-hepatitis B core antibody \[HBc\] immunoglobulin M \[IgM\] positive) or chronic hepatitis B infection with HBV DNA ≥ 2000 IU/mL.
* Active hepatitis C infection (anti-HCV positive with HCV RNA detectable) or anti- HCV positive with HCV RNA undetectable for less than 12 weeks following treatment for HCV.
* Known HIV infection that is not well controlled.
* Evidence of Grade ≥ 1 central nervous system (CNS) haemorrhage.
* Uncontrolled arterial hypertension ≥ 150 and/or ≥ 100 mm Hg.
* Radiographic evidence of major blood vessel invasion or encasement by cancer, intratumour cavitation or direct tumour penetration into the trachea or bronchus.
* Has experienced any arterial thrombotic event, a Grade ≥ 3 bleeding event or has gross haemoptysis.
* Has significant bleeding disorders, serious or nonhealing wound, ulcer or clinically relevant congestive heart failure.
* Has a bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection.
* Under chronic therapy with antiplatelet agents.
* Any prior exposure to anti-vascular endothelial growth factor (VEGF) therapy.
* Known allergy or hypersensitivity to rilvegostomig or any of the excipients of rilvegostomig, cisplatin, carboplatin, paclitaxel or nab-paclitaxel or pemetrexed or ramucirumab.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Research Site

Phoenix, Arizona, United States

Site Status RECRUITING

Research Site

Santa Rosa, California, United States

Site Status RECRUITING

Research Site

Jacksonville, Florida, United States

Site Status RECRUITING

Research Site

Baltimore, Maryland, United States

Site Status NOT_YET_RECRUITING

Research Site

Detroit, Michigan, United States

Site Status NOT_YET_RECRUITING

Research Site

Rochester, Minnesota, United States

Site Status RECRUITING

Research Site

Cleveland, Ohio, United States

Site Status NOT_YET_RECRUITING

Research Site

Providence, Rhode Island, United States

Site Status NOT_YET_RECRUITING

Research Site

Tyler, Texas, United States

Site Status RECRUITING

Research Site

Anderlecht, , Belgium

Site Status NOT_YET_RECRUITING

Research Site

Hasselt, , Belgium

Site Status NOT_YET_RECRUITING

Research Site

Leuven, , Belgium

Site Status NOT_YET_RECRUITING

Research Site

Barretos, , Brazil

Site Status NOT_YET_RECRUITING

Research Site

Fortaleza, , Brazil

Site Status NOT_YET_RECRUITING

Research Site

Natal, , Brazil

Site Status NOT_YET_RECRUITING

Research Site

Pelotas, , Brazil

Site Status NOT_YET_RECRUITING

Research Site

Porto Alegre, , Brazil

Site Status NOT_YET_RECRUITING

Research Site

São Paulo, , Brazil

Site Status NOT_YET_RECRUITING

Research Site

São Paulo, , Brazil

Site Status NOT_YET_RECRUITING

Research Site

Chengdu, , China

Site Status NOT_YET_RECRUITING

Research Site

Chongqing, , China

Site Status NOT_YET_RECRUITING

Research Site

Deyang, , China

Site Status NOT_YET_RECRUITING

Research Site

Fuzhou, , China

Site Status NOT_YET_RECRUITING

Research Site

Guangzhou, , China

Site Status NOT_YET_RECRUITING

Research Site

Jinan, , China

Site Status NOT_YET_RECRUITING

Research Site

Shanghai, , China

Site Status NOT_YET_RECRUITING

Research Site

Shanghai, , China

Site Status NOT_YET_RECRUITING

Research Site

Shenyang, , China

Site Status NOT_YET_RECRUITING

Research Site

Shenzhen, , China

Site Status NOT_YET_RECRUITING

Research Site

Wuhan, , China

Site Status NOT_YET_RECRUITING

Research Site

Wuhan, , China

Site Status NOT_YET_RECRUITING

Research Site

Bordeaux, , France

Site Status NOT_YET_RECRUITING

Research Site

Dijon, , France

Site Status NOT_YET_RECRUITING

Research Site

Limoges, , France

Site Status NOT_YET_RECRUITING

Research Site

Marseille, , France

Site Status NOT_YET_RECRUITING

Research Site

Nantes, , France

Site Status NOT_YET_RECRUITING

Research Site

Nice, , France

Site Status NOT_YET_RECRUITING

Research Site

Paris, , France

Site Status NOT_YET_RECRUITING

Research Site

Batumi, , Georgia

Site Status NOT_YET_RECRUITING

Research Site

Tbilisi, , Georgia

Site Status NOT_YET_RECRUITING

Research Site

Tbilisi, , Georgia

Site Status RECRUITING

Research Site

Tbilisi, , Georgia

Site Status NOT_YET_RECRUITING

Research Site

Tbilisi, , Georgia

Site Status NOT_YET_RECRUITING

Research Site

Tbilisi, , Georgia

Site Status WITHDRAWN

Research Site

München, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Münster, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Oldenburg, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Regensburg, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Würzburg, , Germany

Site Status NOT_YET_RECRUITING

Research Site

Milan, , Italy

Site Status NOT_YET_RECRUITING

Research Site

Milan, , Italy

Site Status NOT_YET_RECRUITING

Research Site

Orbassano, , Italy

Site Status NOT_YET_RECRUITING

Research Site

Pavia, , Italy

Site Status NOT_YET_RECRUITING

Research Site

Roma, , Italy

Site Status NOT_YET_RECRUITING

Research Site

Bunkyō City, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Bunkyō City, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Kashiwa, , Japan

Site Status RECRUITING

Research Site

Kurume-shi, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Kyoto, , Japan

Site Status RECRUITING

Research Site

Niigata, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Shinjuku-ku, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Toyoake-shi, , Japan

Site Status NOT_YET_RECRUITING

Research Site

Kuala Lumpur, , Malaysia

Site Status RECRUITING

Research Site

Kuala Selangor, , Malaysia

Site Status RECRUITING

Research Site

Kuching, , Malaysia

Site Status RECRUITING

Research Site

Singapore, , Malaysia

Site Status RECRUITING

Research Site

Chisinau, , Moldova

Site Status RECRUITING

Research Site

Amsterdam, , Netherlands

Site Status NOT_YET_RECRUITING

Research Site

Groningen, , Netherlands

Site Status NOT_YET_RECRUITING

Research Site

Leiden, , Netherlands

Site Status NOT_YET_RECRUITING

Research Site

Lima, , Peru

Site Status WITHDRAWN

Research Site

Koszalin, , Poland

Site Status NOT_YET_RECRUITING

Research Site

Lodz, , Poland

Site Status NOT_YET_RECRUITING

Research Site

Olsztyn, , Poland

Site Status NOT_YET_RECRUITING

Research Site

Belgrade, , Serbia

Site Status NOT_YET_RECRUITING

Research Site

Kragujevac, , Serbia

Site Status NOT_YET_RECRUITING

Research Site

Niš, , Serbia

Site Status NOT_YET_RECRUITING

Research Site

Seongbuk-Gu, , South Korea

Site Status NOT_YET_RECRUITING

Research Site

Seoul, , South Korea

Site Status NOT_YET_RECRUITING

Research Site

Seoul, , South Korea

Site Status NOT_YET_RECRUITING

Research Site

Seoul, , South Korea

Site Status NOT_YET_RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Research Site

L'Hospitalet de Llobregat, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Madrid, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Madrid, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Pamplona, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Pozuelo de Alarcón, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Valencia, , Spain

Site Status NOT_YET_RECRUITING

Research Site

Taichung, , Taiwan

Site Status RECRUITING

Research Site

Taipei, , Taiwan

Site Status RECRUITING

Research Site

Taipei, , Taiwan

Site Status RECRUITING

Research Site

Bangkok, , Thailand

Site Status RECRUITING

Research Site

Chanthaburi, , Thailand

Site Status NOT_YET_RECRUITING

Research Site

Hat Yai, , Thailand

Site Status NOT_YET_RECRUITING

Research Site

Khon Kaen, , Thailand

Site Status NOT_YET_RECRUITING

Research Site

Rachathewi, , Thailand

Site Status NOT_YET_RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Research Site

Ankara, , Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Research Site

Fatih, , Turkey (Türkiye)

Site Status NOT_YET_RECRUITING

Research Site

Istanbul, , Turkey (Türkiye)

Site Status WITHDRAWN

Countries

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United States Belgium Brazil China France Georgia Germany Italy Japan Malaysia Moldova Netherlands Peru Poland Serbia South Korea Spain Taiwan Thailand Turkey (Türkiye)

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

Phone: 1-877-240-9479

Email: [email protected]

Other Identifiers

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2024-519786-22

Identifier Type: OTHER

Identifier Source: secondary_id

D702KC00001

Identifier Type: -

Identifier Source: org_study_id