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

NCT07098988 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CTL-002-0032024-516792-32-01
• Study Type: interventional
• Target: 107
• Locations: 6 countries
• Sites: 25

Brief 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).

Conditions

Metastatic Non-Squamous Non-Small Cell Lung Cancer; Adult Solid Tumor

Keywords

CTL-002; Visugromab; GDF-15

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  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

  up to 24 months

Secondary Outcomes (13)

• Adverse Events

  up to 27 months

• CR rate

  up to 24 months

• PR rate

  up to 24 months

• DOR

  up to 24 months

• ORR

  up to 24 months

Study Arms (2)

Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A

EXPERIMENTAL

Participants receive Visugromab (recommended dose), Pembrolizumab (200 mg), Pemetrexed (500 mg/m2) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments and Carboplatin target dose Area Under Curve (AUC) 5 (max. dose 750 mg) IV on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for four cycles.

Biological: Visugromab; Biological: Pembrolizumab 200 mg Q3W; Drug: Pemetrexed 500 mg/m^2; Drug: Carboplatin AUC 5

Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B

ACTIVE COMPARATOR

Participants receive matching placebo for visugromab, Pembrolizumab (200 mg), Pemetrexed (500 mg/m2) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments and Carboplatin target dose Area Under Curve (AUC) 5 (max. dose 750 mg) IV on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for four cycles.

Drug: Matching placebo for visugromab; Biological: Pembrolizumab 200 mg Q3W; Drug: Pemetrexed 500 mg/m^2; Drug: Carboplatin AUC 5

Interventions

Visugromab BIOLOGICAL

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.

Also known as: CTL-002

Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A

Matching placebo for visugromab DRUG

Participants receive Matching Placebo intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.

Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B

Pembrolizumab 200 mg Q3W BIOLOGICAL

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.

Also known as: Keytruda®

Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B; Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A

Pemetrexed 500 mg/m^2 DRUG

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.

Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B; Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A

Carboplatin AUC 5 DRUG

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.

Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B; Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• CatalYm GmbH: lead

Study Sites (25)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-2936, United States

NOT YET RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06519, United States

ACTIVE NOT RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

NOT YET RECRUITING

Thorax Clinic Heidelberg

Heidelberg, Baden-Wurttemberg, 69126, Germany

ACTIVE NOT RECRUITING

University Hospital Würzburg

Würzburg, Bavaria, 97080, Germany

ACTIVE NOT RECRUITING

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

Bielefeld, North Rhine-Westphalia, 33611, Germany

ACTIVE NOT RECRUITING

Clinics Essen-Mitte

Essen, North Rhine-Westphalia, 45136, Germany

RECRUITING

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

Großhansdorf, Schleswig-Holstein, 22927, Germany

RECRUITING

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

Meldola, Forli, 47014, Italy

ACTIVE NOT RECRUITING

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

Ravenna, 48121, Italy

RECRUITING

National Cancer Institute Regina Elena, IRCCS

Rome, 00144, Italy

ACTIVE NOT RECRUITING

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

Craiova, Dolj, 200542, Romania

RECRUITING

Gral Medical S.R.L. - Oncofort Hospital

Piteşti, 110283, Romania

ACTIVE NOT RECRUITING

Clinica Polisano S.R.L.

Sibiu, 550253, Romania

RECRUITING

SC Oncomed SRL, Department of Medical Oncology

Timișoara, +40 () 727 774 974, Romania

RECRUITING

University Hospital of Jaen

Jaén, Andalusia, 23007, Spain

NOT YET RECRUITING

Regional University Hospital of Malaga

Málaga, Andalusia, 29010, Spain

RECRUITING

University Hospital Virgen Macarena

Seville, Andalusia, 41009, Spain

ACTIVE NOT RECRUITING

University Hospital Complex of Santiago (CHUS)

Santiago de Compostela, Galicia, 15706, Spain

RECRUITING

University Hospital 12 de Octubre

Madrid, Madrid, 28041, Spain

ACTIVE NOT RECRUITING

University Hospital Lucus Augusti (HULA)

Lugo, 27003, Spain

RECRUITING

University Hospital Basel

Basel, Basel, 4031, Switzerland

RECRUITING

Fribourg Cantonal Hospital

Fribourg, Canton of Fribourg, 1708, Switzerland

ACTIVE NOT RECRUITING

Cantonal Hospital Saint Gallen, Clinic of Oncology and Hematology

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

RECRUITING

MeSH Terms

Interventions

pembrolizumab; Pemetrexed

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Felix Lichtenegger, MD

  CatalYm GmbH

  STUDY DIRECTOR

Central Study Contacts

Felix Lichtenegger, MD

CONTACT

+49 89 200066440; regulatory-003@catalym.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Participants, Investigator and Site trial team, Sponsor and Service Providers' trial teams (including Imaging vendor) are blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part A: Safety Run-In Part B and Part C: Randomized Part The randomized part consists of two arms: Visugromab + ICT (Arm A) and Placebo + ICT (Arm B) Participants will be allocated in 2:1 ratio to treatment arm A or B.

Study Record Dates

• First Submitted: July 10, 2025
• First Posted: August 1, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): March 31, 2029
• Study Completion (Estimated): March 31, 2031
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (3); ES (6); DE (5); US (4); RO (4); IT (3)