RecruitingPhase 1Phase 2NCT06996782

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

A Phase Ib/II Open-Label, Multicentre Platform Study Evaluating Novel Combinations in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer


Sponsor

AstraZeneca

Enrollment

152 participants

Start Date

Nov 24, 2025

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria10

  • 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.
  • 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 Criteria28

  • 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.
  • 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

DRUGRilvegostomig

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

DRUGCisplatin

Cisplatin will be administered as SoC as an IV infusion.

DRUGCarboplatin

Carboplatin will be administered as SoC as an IV infusion.

DRUGPemetrexed

Pemetrexed will be administered as SoC as an IV infusion.

DRUGPaclitaxel

Paclitaxel will be administered as SoC as an IV infusion.

DRUGNab-paclitaxel

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

DRUGRamucirumab

Ramucirumab will be administered as an IV infusion.


Locations(105)

Research Site

Kyoto, Japan

Research Site

Phoenix, Arizona, United States

Research Site

Santa Rosa, California, United States

Research Site

Jacksonville, Florida, United States

Research Site

Baltimore, Maryland, United States

Research Site

Detroit, Michigan, United States

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Rochester, Minnesota, United States

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Cleveland, Ohio, United States

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Providence, Rhode Island, United States

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Providence, Rhode Island, United States

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Tyler, Texas, United States

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Anderlecht, Belgium

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Hasselt, Belgium

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Leuven, Belgium

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Barretos, Brazil

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Fortaleza, Brazil

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Natal, Brazil

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Pelotas, Brazil

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Porto Alegre, Brazil

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São Paulo, Brazil

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São Paulo, Brazil

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Chengdu, China

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Chongqing, China

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Deyang, China

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Fuzhou, China

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Guangzhou, China

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Jinan, China

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Shanghai, China

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Shanghai, China

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Shenyang, China

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Shenzhen, China

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Wuhan, China

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Wuhan, China

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Bordeaux, France

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Dijon, France

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Limoges, France

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Marseille, France

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Nantes, France

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Nice, France

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Paris, France

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Batumi, Georgia

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Tbilisi, Georgia

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Tbilisi, Georgia

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Tbilisi, Georgia

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Tbilisi, Georgia

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Tbilisi, Georgia

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München, Germany

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Münster, Germany

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Oldenburg, Germany

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Regensburg, Germany

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Würzburg, Germany

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Milan, Italy

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Milan, Italy

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Orbassano, Italy

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Pavia, Italy

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Roma, Italy

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Bunkyō City, Japan

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Bunkyō City, Japan

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Kashiwa, Japan

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Kurume-shi, Japan

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Niigata, Japan

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Shinjuku-ku, Japan

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Toyoake-shi, Japan

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Kuala Lumpur, Malaysia

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Kuala Selangor, Malaysia

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Kuching, Malaysia

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Singapore, Malaysia

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Chisinau, Moldova

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Amsterdam, Netherlands

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Groningen, Netherlands

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Leiden, Netherlands

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Lima, Peru

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Koszalin, Poland

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Lodz, Poland

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Olsztyn, Poland

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Belgrade, Serbia

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Belgrade, Serbia

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Kragujevac, Serbia

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Niš, Serbia

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Seongbuk-Gu, South Korea

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Seoul, South Korea

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Seoul, South Korea

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Seoul, South Korea

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Seoul, South Korea

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Barcelona, Spain

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Barcelona, Spain

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L'Hospitalet de Llobregat, Spain

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Madrid, Spain

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Madrid, Spain

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Pamplona, Spain

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Pozuelo de Alarcón, Spain

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Valencia, Spain

Research Site

Valencia, Spain

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Taichung, Taiwan

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Taipei, Taiwan

Research Site

Taipei, Taiwan

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Bangkok, Thailand

Research Site

Chanthaburi, Thailand

Research Site

Hat Yai, Thailand

Research Site

Khon Kaen, Thailand

Research Site

Rachathewi, Thailand

Research Site

Ankara, Turkey (Türkiye)

Research Site

Ankara, Turkey (Türkiye)

Research Site

Fatih, Turkey (Türkiye)

Research Site

Istanbul, Turkey (Türkiye)

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NCT06996782


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