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NCT07098988PHASE2Recruiting

Trial Investigating Visugromab in Combination With Immunochemotherapy in 1L Treatment of Participants With Metastatic NSCLC

CatalYm GmbH

Start Date

8/1/2025

Completion Date

3/31/2031

Summary

This is an exploratory, signal finding, randomized, placebo-controlled, blinded, multi-center Phase 2b trial of the anti GDF-15 antibody Visugromab (CTL-002) versus Placebo, combined with Immunochemotherapy (ICT: Pembrolizumab, Pemetrexed, Carboplatin) in the first-line treatment of participants with newly diagnosed metastatic non-squamous NSCLC. The trial consists of 3 Parts, a non-randomized Safety-run-in part (Part A) and the subsequent randomized Ph2b trial with 2 treatment arms. After the treatment of 15 participants with visugromab at the expansion dose, an interim safety and preliminary efficacy analysis will be conducted (Part B), followed by the treatment of the remaining participants (Part C).

Eligibility Criteria

Age Range: 18 years to No maximum

Main Inclusion Criteria: * Histologically confirmed, newly diagnosed stage IV non-squamous NSCLC. * Demonstrated absence of actionable mutations (e.g., EGFR, ALK, among others) that suggest/require treatment with available targeted agent. * Measurable disease determined by the local site Investigator/radiology by their assessment per RECIST v1.1. * Have not received prior systemic treatment for advanced/metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease and did not contain any PD 1/PD L1 directed CPI therapy. * Availability of locally determined PD L1 TPS, determined with a test validated for this purpose, from a tumor tissue biopsy obtained after any potential prior systemic treatment for this disease. Participants with PD-L1 TPS ≥ 50% can only be enrolled in case CPI monotherapy is not clinically indicated. * Availability of a tissue/histological biopsy for translational research investigations and Informed Consent Form (ICF) for biopsy release for translational research signed by participant. The biopsy has to be obtained after any potential prior systemic treatment for this disease and be available for shipment. A cytological sample is not accepted. * Age ≥ 18 years on the day of signing the informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Adequate organ function (bone marrow, hepatic, renal function and coagulation). Main Exclusion Criteria: * Presence of predominantly squamous cell histology or predominantly neuroendocrine histology NSCLC (mixed tumors will be categorized by the predominant cell type) or presence of small cell lung cancer elements (ineligibility independent of percentage). * Any acute or chronic major tissue injury that may require maintained GDF 15 function for tissue protection as per Investigator assessment (diagnosed with myocardial infarction, or liver, kidney or other major organ failure, all within \< 3 months prior to planned treatment start). * Major surgery (defined as a surgery which requires general anesthetic and/or involves opening of body cavities), within 4 weeks of the first dose of study drug. * Received potentially curative radiation therapy to the lung that is \> 30 Gy within 6 months prior to the first dose of study drug. * Received or completed any focal radiotherapy for symptoms within 28 days of the first dose of study drug. * Expected to require any other form of antineoplastic therapy while on trial. * Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction. * Known history of prior malignancy with the exception that the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy. * Known or detected clinically active central nervous system (CNS) involvement by NSCLC or other tumors, e.g., with symptomatic metastases and/or carcinomatous meningitis. Participants with CNS involvement may be enrolled with mandatory regular imaging of the brain under protocol-defined conditions. * Have one of the following cardiovascular risk factors: myocardial infarction in the past 3 months before planned treatment start; uncontrolled heart failure; uncontrolled ventricular arrhythmia; QT interval corrected for heart rate using Fridericia's formula interval ≥ 470 ms regardless of sex; peri/myocarditis in the past 3 months before planned treatment start; history of ischemic stroke in the past 3 months before planned treatment start. * Any active autoimmune that has required systemic treatment in the past 3 months before planned treatment start (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). * Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes. * Has interstitial lung disease or a history of non-infectious pneumonitis that required systemic steroids or current pneumonitis. * Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.

Interventions

BIOLOGICAL

Visugromab

DRUG

Matching placebo for visugromab

BIOLOGICAL

Pembrolizumab 200 mg Q3W

DRUG

Pemetrexed 500 mg/m^2

DRUG

Carboplatin AUC 5

Interested in This Trial?

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Conditions

Metastatic Non-Squamous Non-Small Cell Lung CancerAdult Solid Tumor

Locations

University of Alabama at Birmingham

Birmingham, Alabama 35294-2936

United States

USC Norris Comprehensive Cancer Center

Los Angeles, California 90033

United States

Yale Cancer Center

New Haven, Connecticut 06519

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

NYU Longone Health

New York, New York 10016

United States

Duke University Medical Center

Durham, North Carolina 27710

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

Thorax Clinic Heidelberg

Heidelberg, Baden-Wurttemberg 69126

Germany

University Hospital Würzburg

Würzburg, Bavaria 97080

Germany

Evangelical Hospital Bethel, Clinic for Internal Medicine, Hematology/Oncology, Palliative Medicine Johannesstift

Bielefeld, North Rhine-Westphalia 33611

Germany

Clinics Essen-Mitte

Essen, North Rhine-Westphalia 45136

Germany

Foundation Bethanien Moers

Moers, North Rhine-Westphalia 47441

Germany

Großhansdorf Hospital - Clinical Center for Pulmonology and Thoracic Surgery, Department of Thoracic Oncology

Großhansdorf, Schleswig-Holstein 22927

Germany

Institute of Romagna for Cancer Research " Dino Amadori" - IRCCS IRST

Meldola, Forli 47014

Italy

Oncology Reference Center

Aviano, 33081

Italy

Local Health Unit of Romagna - Santa Maria delle Croci Hospital of Ravenna, Onco-Hematology Department

Ravenna, 48121

Italy

National Cancer Institute Regina Elena, IRCCS

Rome, 00144

Italy

MED-Polonia, Sp. z o.o. (LLC)

Poznan, 60-693

Poland

Specialist Hospital in Prabuty Sp. z o.o. (LLC), Department of Pulmonology

Prabuty, 82-550

Poland

"Sf. Nectarie" Oncology Center, Department of Medical Oncology

Craiova, Dolj 200542

Romania

Gral Medical S.R.L. - Oncofort Hospital

Piteşti, 110283

Romania

Clinica Polisano S.R.L.

Sibiu, 550253

Romania

SC Oncomed SRL, Department of Medical Oncology

Timișoara, +40 () 727 774 974

Romania

University Hospital of Jaen

Jaén, Andalusia 23007

Spain

Regional University Hospital of Malaga

Málaga, Andalusia 29010

Spain

University Hospital Virgen Macarena

Seville, Andalusia 41009

Spain

University Hospital Virgen del Rocio (HUVR)

Seville, Andalusia 41013

Spain

University Hospital Marques de Valdecilla (HUMV)

Santander, Cantabria 39008

Spain

Hospital del Mar

Barcelona, Catalonia 08003

Spain

Hospital Quiron Dexeus Barcelona

Barcelona, Catalonia 08028

Spain

University Clinic of Navarra - Pamplona

Pamplona, Chartered Community of Navarre 31008

Spain

University Hospital Complex of Santiago (CHUS)

Santiago de Compostela, Galicia 15706

Spain

START- Rioja

Rioja, La Rioja 26006

Spain

University Hospital 12 de Octubre

Madrid, Madrid 28041

Spain

University Hospital HM Sanchinarro

Madrid, Madrid 28050

Spain

University Hospital Lucus Augusti (HULA)

Lugo, 27003

Spain

MD Anderson International Cancer Center Spain

Madrid, 28033

Spain

University Hospital Basel

Basel, Basel 4031

Switzerland

Fribourg Cantonal Hospital

Fribourg, Canton of Fribourg 1708

Switzerland

Cantonal Hospital Saint Gallen, Clinic of Oncology and Hematology

Sankt Gallen, Canton of St. Gallen 9007

Switzerland