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NCT06996782PHASE1, PHASE2Recruiting

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

AstraZeneca

Start Date

11/24/2025

Completion Date

2/23/2029

Summary

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

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 a sub-study (sub-study 2) focused on a specific treatment that 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. The originally planned Sub-study 1 was withdrawn (cancelled) and will not be conducted. 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.

Eligibility Criteria

Age Range: 18 years to No maximum

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. Inclusion Criteria for Sub Study 2: * Programmed death-ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 1% (per local report). * Adequate coagulation and urinalysis. * Minimum body weight of 30 kg. 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. * Presence of small cell and neuroendocrine histology components. * Any severe or uncontrolled systemic diseases, including uncontrolled hypertension, and active bleeding diseases, ongoing or active known infection; interstitial lung disease/pneumonitis (of any grade); unstable and/or symptomatic venous thromboembolism, 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 5 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. * Persistent toxicities (common terminology criteria for adverse events \[CTCAE\] ≥ Grade 2) caused by previous anti-cancer therapy, excluding alopecia. * Spinal cord compression or symptomatic brain metastases. * 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. Exclusion Criteria for Sub Study 2: * 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 human immunodeficiency virus (HIV) infection that is not well controlled. * Evidence of Grade ≥ 1 central nervous system (CNS) haemorrhage. * Uncontrolled arterial hypertension ≥ 150 mm Hg (systolic) and/or ≥ 100 mm Hg (diastolic). * Has radiologically documented evidence of major blood vessel invasion or encasement by cancer, or major airway invasion by cancer or intra-tumour cavitation. * 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. * Has cirrhosis at a level of Child-Pugh B (or worse), or cirrhosis (any degree) and a history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. * Prior systemic therapy received for advanced or mNSCLC. * Prior exposure to an anti-T-cell immunoreceptor with Ig and Immunoreceptor Tyrosine-based Inhibition Motif domains (TIGIT) therapy or immune-oncology agent such as anti-programmed cell death protein 1 (PD-1), anti-PD-L1, or anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4), or any other anti-cancer therapy targeting immune-regulatory receptors or mechanisms. * Chronic therapy with antiplatelet agents. * Prior exposure to anti-vascular endothelial growth factor (VEGF) therapy. * Medical contraindication to protocol-specified platinum doublet regimens or ramucirumab. * Known allergy or hypersensitivity to rilvegostomig or any of the excipients of rilvegostomig, cisplatin, carboplatin, paclitaxel or nab-paclitaxel or pemetrexed or ramucirumab.

Interventions

DRUG

Rilvegostomig

DRUG

Cisplatin

DRUG

Carboplatin

DRUG

Pemetrexed

DRUG

Paclitaxel

DRUG

Nab-paclitaxel

DRUG

Ramucirumab

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Conditions

Advanced or Metastatic Non-small Cell Lung Cancer

Locations

Research Site

Phoenix, Arizona 85054

United States

Research Site

Santa Rosa, California 95403

United States

Research Site

Jacksonville, Florida 32224

United States

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Baltimore, Maryland 21201

United States

Research Site

Detroit, Michigan 48202

United States

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Rochester, Minnesota 55905

United States

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Cleveland, Ohio 44106

United States

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Providence, Rhode Island 02903

United States

Research Site

Providence, Rhode Island 02906

United States

Research Site

Tyler, Texas 75708

United States

Research Site

Anderlecht, 1070

Belgium

Research Site

Hasselt, 3500

Belgium

Research Site

Leuven, 3000

Belgium

Research Site

Barretos, 14784-400

Brazil

Research Site

Fortaleza, 60336-232

Brazil

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Natal, 59075-740

Brazil

Research Site

Pelotas, 096015-280

Brazil

Research Site

Porto Alegre, 90035-903

Brazil

Research Site

São Paulo, 01246-000

Brazil

Research Site

São Paulo, 05651-901

Brazil

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Chengdu, 610041

China

Research Site

Chongqing, 400072

China

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Deyang, 618000

China

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Fuzhou, 350014

China

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Guangzhou, 510405

China

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Jinan, 250013

China

Research Site

Shanghai, 200433

China

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Shanghai, 201114

China

Research Site

Shenyang, 110015

China

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Shenzhen, 518116

China

Research Site

Wuhan, 430022

China

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Wuhan, 430060

China

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Bordeaux, 33076

France

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Dijon, 21079

France

Research Site

Limoges, 87000

France

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Marseille, 13015

France

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Nantes, 44093

France

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Nice, 06189

France

Research Site

Paris, 75005

France

Research Site

Batumi, 6010

Georgia

Research Site

Tbilisi, 0112

Georgia

Research Site

Tbilisi, 0114

Georgia

Research Site

Tbilisi, 0144

Georgia

Research Site

Tbilisi, 0186

Georgia

Research Site

München, 81675

Germany

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Münster, 48149

Germany

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Oldenburg, 26121

Germany

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Regensburg, 93053

Germany

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Würzburg, 97080

Germany

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Milan, 20141

Italy

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Milan, 20162

Italy

Research Site

Orbassano, 10043

Italy

Research Site

Pavia, 27100

Italy

Research Site

Roma, 00168

Italy

Research Site

Bunkyō City, 113-8431

Japan

Research Site

Bunkyō City, 113-8677

Japan

Research Site

Kashiwa, 277-8577

Japan

Research Site

Kurume-shi, 830-0011

Japan

Research Site

Kyoto, 602-8566

Japan

Research Site

Niigata, 951-8566

Japan

Research Site

Shinjuku-ku, 162-8655

Japan

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Toyoake-shi, 470-1192

Japan

Research Site

Kuala Lumpur, 59100

Malaysia

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Kuala Selangor, 62250

Malaysia

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Kuching, 93586

Malaysia

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Singapore, 329563

Malaysia

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Chisinau, MD-2025

Moldova

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Amsterdam, 1066CX

Netherlands

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Groningen, 9713 GZ

Netherlands

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Leiden, 2333 ZA

Netherlands

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Lima, 15036

Peru

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Koszalin, 75-581

Poland

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Lodz, 93-338

Poland

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Olsztyn, 10-357

Poland

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Belgrade, 11000

Serbia

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Kragujevac, 34000

Serbia

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Niš, 18000

Serbia

Research Site

Seongbuk-Gu, 2841

South Korea

Research Site

Seoul, 03080

South Korea

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Seoul, 05505

South Korea

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Seoul, 3722

South Korea

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Seoul, 6351

South Korea

Research Site

Barcelona, 08035

Spain

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Barcelona, 08036

Spain

Research Site

L'Hospitalet de Llobregat, 08908

Spain

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Madrid, 28034

Spain

Research Site

Madrid, 28041

Spain

Research Site

Pamplona, 31008

Spain

Research Site

Pozuelo de Alarcón, 28223

Spain

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Valencia, 46009

Spain

Research Site

Valencia, 46010

Spain

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Taichung, 40201

Taiwan

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Taipei, 110

Taiwan

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Taipei, 11696

Taiwan

Research Site

Bangkok, 10700

Thailand

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Chanthaburi, 22000

Thailand

Research Site

Hat Yai, 90110

Thailand

Research Site

Khon Kaen, 40002

Thailand

Research Site

Rachathewi, 10400

Thailand

Research Site

Ankara, 06230

Turkey (Türkiye)

Research Site

Ankara, 6200

Turkey (Türkiye)

Research Site

Fatih, 34093

Turkey (Türkiye)

Research Site

Istanbul, 34752

Turkey (Türkiye)