Visugromab added to first-line immunochemotherapy for metastatic non-squamous NSCLC

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2b trial of the anti–GDF-15 antibody visugromab given with first-line immunochemotherapy (pembrolizumab, pemetrexed, carboplatin) in newly diagnosed metastatic non-squamous NSCLC. The study begins with a non-randomized safety run-in (Part A), includes an interim safety and preliminary efficacy analysis after 15 participants at the expansion dose (Part B), and then proceeds to a randomized expansion phase (Part C). Key entry requirements include no actionable driver mutations, measurable disease by RECIST v1.1, and available local PD-L1 TPS; prior adjuvant/neoadjuvant therapy is allowed if completed >12 months before metastasis. Participants are randomized to receive visugromab or matching placebo alongside standard immunochemotherapy with blinded assessment of safety and early efficacy signals.

Why it matters

Who can join: the full rules

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.

Where it's running

• University of Alabama at Birmingham
  Birmingham, Alabama, United States Recruiting
• USC Norris Comprehensive Cancer Center
  Los Angeles, California, United States Recruiting
• Smilow Cancer Center, Derby
  Derby, Connecticut, United States Recruiting
• Smilow Cancer Center, Guilford
  Guilford, Connecticut, United States Recruiting
• Yale Cancer Center
  New Haven, Connecticut, United States Recruiting
• Smilow Cancer Hospital - North Haven
  North Haven, Connecticut, United States Recruiting

+1 more sites. See ClinicalTrials.gov for the full list.

Study contacts

• Study coordinator: Felix Lichtenegger, MD
• Email: regulatory-003@catalym.com
• Phone: +49 89 200066440

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Visugromab plus nivolumab, with or without docetaxel, for second-line treatment of metastatic non-squamous non-small cell lung cancer

  This trial tests whether adding the anti-GDF-15 antibody visugromab to nivolumab, with or without docetaxel, helps people with metastatic non-squamous NSCLC whose cancer progressed after first-line treatment that included a checkpoint inhibitor.

  Recruiting at 36 sites Phase 2 CatalYm GmbH · Birmingham, Alabama and 35 other locations · NCT07246863

• First-line treatment with pembrolizumab, pemetrexed, and platinum with or without zoldonrasib for metastatic non-squamous NSCLC

  This trial tests whether adding zoldonrasib to standard pembrolizumab and platinum chemotherapy helps people with untreated metastatic non-squamous NSCLC that has a RAS G12D mutation.

  Recruiting at 4 sites Phase 3 Revolution Medicines, Inc. · Anchorage, Alaska and 3 other locations · NCT07777822

• Lenvatinib and Pembrolizumab With or Without SBRT for Metastatic Kidney Cancer

  This study tests whether adding SBRT to standard lenvatinib plus pembrolizumab helps people with metastatic kidney cancer who have stable disease after initial treatment.

  Recruiting at 8 sites Phase 2 Kidney Cancer Research Bureau · Kazan' and 7 other locations · NCT07928167

• Bladder cancer: test a biomarker-guided plan after neoadjuvant therapy

  This phase 2 study tests a biomarker- and response-guided plan to preserve the bladder in patients with muscle-invasive bladder cancer after neoadjuvant therapy.

  Recruiting Phase 2 Fox Chase Cancer Center · Philadelphia, Pennsylvania · NCT07908979

• Peripheral neuropathy during perioperative therapy with enfortumab vedotin and pembrolizumab in muscle-invasive urothelial cancer

  This study follows adults with muscle-invasive urothelial cancer to see how nerve-related side effects develop when people receive enfortumab vedotin and pembrolizumab around surgery as part of standard care.

  Recruiting at 3 sites Comprehensive Cancer Center Munich (CCCM) · Munich, Bavaria and 2 other locations · NCT07870577

• Sacituzumab Tirumotecan plus Pembrolizumab in advanced biliary tract cancer

  This study tests whether the combination of Sacituzumab Tirumotecan and Pembrolizumab can help people with advanced biliary tract cancer who have already had at least one approved therapy fail.

  Recruiting Phase 2 Peking Union Medical College Hospital · Beijing, Beijing Municipality · NCT07850791

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.