Visugromab: Participants receive Visugromab (recommended dose) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
Matching placebo for visugromab: Participants receive Matching Placebo intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
Pembrolizumab 200 mg Q3W: Participants receive Pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments after visugromab infusion.
Pemetrexed 500 mg/m^2: Participants receive Pemetrexed 500 mg/m\^2 IV on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
Carboplatin AUC 5: Participants receive Carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) on Day 1 of each 21-day cycle for four cycles.
Study 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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Objective Response Rate — up to 24 months Percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator at any time during the core trial period
Trial sites (42)
Facility
City
Region
Status
University of Alabama at Birmingham
Birmingham
Alabama
Recruiting
USC Norris Comprehensive Cancer Center
Los Angeles
California
Recruiting
Yale Cancer Center
New Haven
Connecticut
Recruiting
Moffitt Cancer Center
Tampa
Florida
Recruiting
NYU Longone Health
New York
New York
Recruiting
Duke University Medical Center
Durham
North Carolina
Recruiting
Medical University of South Carolina
Charleston
South Carolina
Recruiting
Thorax Clinic Heidelberg
Heidelberg
Baden-Wurttemberg
Recruiting
University Hospital Würzburg
Würzburg
Bavaria
Recruiting
Evangelical Hospital Bethel, Clinic for Internal Medicine, Hematology/Oncology, Palliative Medicine Johannesstift
Bielefeld
North Rhine-Westphalia
Recruiting
Clinics Essen-Mitte
Essen
North Rhine-Westphalia
Recruiting
Foundation Bethanien Moers
Moers
North Rhine-Westphalia
Recruiting
Großhansdorf Hospital - Clinical Center for Pulmonology and Thoracic Surgery, Department of Thoracic Oncology
Großhansdorf
Schleswig-Holstein
Recruiting
Institute of Romagna for Cancer Research " Dino Amadori" - IRCCS IRST
Meldola
Forli
Recruiting
National Cancer Institute, IRCCS
Milan
Milan
Recruiting
Oncology Reference Center
Aviano
Italy
Recruiting
Local Health Unit of Romagna - Santa Maria delle Croci Hospital of Ravenna, Onco-Hematology Department
Ravenna
Italy
Recruiting
National Cancer Institute Regina Elena, IRCCS
Rome
Italy
Recruiting
MED-Polonia, Sp. z o.o. (LLC)
Poznan
Poland
Recruiting
Specialist Hospital in Prabuty Sp. z o.o. (LLC), Department of Pulmonology
Prabuty
Poland
Recruiting
"Sf. Nectarie" Oncology Center, Department of Medical Oncology
Craiova
Dolj
Recruiting
Gral Medical S.R.L. - Oncofort Hospital
Piteşti
Romania
Recruiting
Clinica Polisano S.R.L.
Sibiu
Romania
Recruiting
SC Oncomed SRL, Department of Medical Oncology
Timișoara
Romania
Recruiting
University Hospital of Jaen
Jaén
Andalusia
Recruiting
Regional University Hospital of Malaga
Málaga
Andalusia
Recruiting
University Hospital Virgen Macarena
Seville
Andalusia
Recruiting
University Hospital Virgen del Rocio (HUVR)
Seville
Andalusia
Recruiting
University Hospital Marques de Valdecilla (HUMV)
Santander
Cantabria
Recruiting
Hospital del Mar
Barcelona
Catalonia
Recruiting
Hospital Quiron Dexeus Barcelona
Barcelona
Catalonia
Recruiting
University Clinic of Navarra - Pamplona
Pamplona
Chartered Community of Navarre
Recruiting
University Hospital Complex of Santiago (CHUS)
Santiago de Compostela
Galicia
Recruiting
START- Rioja
Rioja
La Rioja
Recruiting
University Clinic of Navarra - Madrid
Madrid
Madrid
Recruiting
University Hospital 12 de Octubre
Madrid
Madrid
Recruiting
University Hospital HM Sanchinarro
Madrid
Madrid
Recruiting
University Hospital Lucus Augusti (HULA)
Lugo
Spain
Recruiting
MD Anderson International Cancer Center Spain
Madrid
Spain
Recruiting
University Hospital Basel
Basel
Basel
Recruiting
+ 2 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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