Authorised Therapeutic exploratory (Phase II) Metastatic non-squamous non-small cell lung cancer

A phase 2 placebo-controlled trial to investigate visugromab in combination with immunochemotherapy (ICT) in first-line treatment of participants with metastatic non-squamous non-small cell lung cancer (NSCLC)

EU CTIS ID: 2024-516792-32-01

What this study is testing

To investigate the antitumoral effect in participants treated with visugromab plus ICT versus placebo plus ICT

Therapeutic exploratory (Phase II)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1. Histologically confirmed, newly diagnosed stage IV non-squamous NSCLC
10. Adequate organ function, defined as: - Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500 /μL; Platelets ≥ 100,000 /μL; Hemoglobin ≥ 10.0 g/dL after ≥ 4 weeks without transfusions - Renal: Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m^2 - Hepatic: Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN; Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN for participants with liver metastases). - Endocrine: Thyroid stimulating hormone (TSH) within normal range including participants with thyroid hormone substitution. If TSH is not within normal range at baseline, the participant will still be eligible if total T3 or free T3 and free T4 are within the normal range - Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy; Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy; No evidence for clinically relevant hypo- or hypercoagulability or presence of clinically relevant thrombosis/thrombotic event.
11. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to receiving the first dose of trial medication.
12. Females of childbearing potential must be willing to use a highly effective method of contraception from 14 days before start of IMP and for the course of the trial through 120 days after the last dose of pembrolizumab, or 150 days after last dose of visugromab/placebo or through 180 days after last dose of chemotherapeutic agents as specified in the protocol, whatever comes later.
13. Male participants with a female partner(s) of child-bearing potential must agree to use a highly effective method of contraception, starting with the first dose of pembrolizumab, or 150 days after last dose of visugromab/placebo through 120 days after the last dose of trial therapy or through 180 days after last dose of chemotherapeutic agents as specified in the protocol, whatever comes later. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
14. Ability to understand the purpose of the trial and voluntary provision of a signed and dated informed consent prior to performing any protocol-related procedures (including Screening evaluations) and ability to comply with the trial procedures (including completion of the electronic questionnaire on patient-reported outcome).

You likely can't join if

1. 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).
18. Unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs, other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
19. Unable or unwilling to take folic acid or vitamin B12 supplementation.
2. Currently participating in a clinical trial or receiving any investigational therapy or have participated in a trial of an investigational agent in the past 4 weeks or used an investigational device for any disease within 4 weeks prior to administration of any IMP.
20. Presence of active infection requiring systemic therapy.
21. Known history of Human Immunodeficiency Virus (HIV; known HIV 1/2 antibody [Ab] positive).

See the full eligibility criteria

Who can join

1. Histologically confirmed, newly diagnosed stage IV non-squamous NSCLC
10. Adequate organ function, defined as: - Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500 /μL; Platelets ≥ 100,000 /μL; Hemoglobin ≥ 10.0 g/dL after ≥ 4 weeks without transfusions - Renal: Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min/1.73m^2 - Hepatic: Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN; Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN for participants with liver metastases). - Endocrine: Thyroid stimulating hormone (TSH) within normal range including participants with thyroid hormone substitution. If TSH is not within normal range at baseline, the participant will still be eligible if total T3 or free T3 and free T4 are within the normal range - Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy; Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy; No evidence for clinically relevant hypo- or hypercoagulability or presence of clinically relevant thrombosis/thrombotic event.
11. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to receiving the first dose of trial medication.
12. Females of childbearing potential must be willing to use a highly effective method of contraception from 14 days before start of IMP and for the course of the trial through 120 days after the last dose of pembrolizumab, or 150 days after last dose of visugromab/placebo or through 180 days after last dose of chemotherapeutic agents as specified in the protocol, whatever comes later.
13. Male participants with a female partner(s) of child-bearing potential must agree to use a highly effective method of contraception, starting with the first dose of pembrolizumab, or 150 days after last dose of visugromab/placebo through 120 days after the last dose of trial therapy or through 180 days after last dose of chemotherapeutic agents as specified in the protocol, whatever comes later. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
14. Ability to understand the purpose of the trial and voluntary provision of a signed and dated informed consent prior to performing any protocol-related procedures (including Screening evaluations) and ability to comply with the trial procedures (including completion of the electronic questionnaire on patient-reported outcome).
2. Demonstrated absence of actionable mutations (e.g. EGFR, ALK, among others) that suggest/require treatment with an available targeted agent.
3. Measurable disease as per the local reading provided to the Investigator by a qualified radiologist based on an assessment per RECIST v1.1. If a target lesion is located in a previously irradiated area, it will be considered measurable if progression (or non-reduced size in the past 12 weeks) has been demonstrated in such a lesion.
4. 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 checkpoint inhibitor (CPI) therapy.
5. 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.
6. Availability of a tissue/histological biopsy (formalin-fixed paraffin-embedded block preferred) 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.
7. Age ≥ 18 years on the day of signing the informed consent.
8. Life expectancy of at least 3 months as assessed by the Investigator.
9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.

What rules you out

1. 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).
18. Unable to interrupt aspirin or other non-steroidal anti-inflammatory drugs, other than an aspirin dose ≤ 1.3 g per day, for a 5-day period (8-day period for long-acting agents, such as piroxicam).
19. Unable or unwilling to take folic acid or vitamin B12 supplementation.
2. Currently participating in a clinical trial or receiving any investigational therapy or have participated in a trial of an investigational agent in the past 4 weeks or used an investigational device for any disease within 4 weeks prior to administration of any IMP.
20. Presence of active infection requiring systemic therapy.
21. Known history of Human Immunodeficiency Virus (HIV; known HIV 1/2 antibody [Ab] positive).
22. Known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive IgM HCV antibody result or known quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay.
23. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant’s participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
24. Symptomatic ascites or pleural effusion(s). A participant who is clinically stable following treatment for these conditions (including therapeutic fluid removal) is eligible.
25. Interstitial lung disease or a history of non-infectious pneumonitis that required systemic steroids or current pneumonitis.
27. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.
10. 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.
28. Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial (including severe alcoholism) or had a recent history (within the last 6 months before planned treatment start) of such abuse, or any other condition that as per Investigator view would not permit trial participation.
29. Participant is under legal guardianship.
3. 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).
4. 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 IMP.
5. Received radiation therapy to the lung that is > 30 Gy within 6 months prior to the first dose of IMP.
6. Received or completed any focal radiotherapy for symptoms within 28 days of the first dose of IMP.
7. Expected to require any other form of antineoplastic therapy while on trial.
8. Received a live or live-attenuated vaccination within 30 days of planned treatment start.
9. Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction.
26. History of stem cell/solid organ transplant
11. 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 as a site of disease if all CNS lesions fulfill one of the following criteria: - CNS lesions following prior radiotherapy or surgery: Clinically stable for at least 14 days post stereotactic radiotherapy, at least 14 days post whole brain irradiation, and at least 28 days post surgery as documented by clinical assessment without evidence of new or enlarging brain metastases. Participants have to be off steroids for 5 days prior to first dose of trial medication. - Known untreated, but asymptomatic CNS lesions (i.e., no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, no lesion > 1.5 cm in diameter): Clinically stable for at least 4 weeks before planned treatment start.
12. Have one of the following cardio-vascular risk factors: - Myocardial infarction in the past 6 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. - A peri/myocarditis in the past 3 months before planned treatment start. - A history of ischemic stroke in the past 3 months before planned treatment start.
13. Prior severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
14. Known sensitivity to any component of pembrolizumab, or pemetrexed, or carboplatin.
15. An active autoimmune disease 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). Local corticosteroid treatment or replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
16. Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes.
17. Chronic systemic corticosteroid treatment for other reasons. Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections are not excluded from participation.

The study team makes the final eligibility decision.

Where it's taking place

United States
Switzerland

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States; Switzerland. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.