VISUGROMAB for Non-small cell lung cancer (non-squamous) | Metastatic non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 1. Histologically confirmed, newly diagnosed stage IV non-squamous NSCLC"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 11. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to receiving the first dose of trial medication."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 2. Demonstrated absence of actionable mutations (e.g. EGFR, ALK, among others) that suggest/require treatment with an available targeted agent."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 7. Age ≥ 18 years on the day of signing the informed consent."}
• {"criterion_text":"- 8. Life expectancy of at least 3 months as assessed by the Investigator."}
• {"criterion_text":"- 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1."}

Exclusion criteria

• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 13. Prior severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb)."}
• {"criterion_text":"- 14. Known sensitivity to any component of pembrolizumab, or pemetrexed, or carboplatin."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 16. Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 19. Unable or unwilling to take folic acid or vitamin B12 supplementation."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 20. Presence of active infection requiring systemic therapy."}
• {"criterion_text":"- 21. Known history of Human Immunodeficiency Virus (HIV; known HIV 1/2 antibody [Ab] positive)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 24. Symptomatic ascites or pleural effusion(s). A participant who is clinically stable following treatment for these conditions (including therapeutic fluid removal) is eligible."}
• {"criterion_text":"- 25. Interstitial lung disease or a history of non-infectious pneumonitis that required systemic steroids or current pneumonitis."}
• {"criterion_text":"- 26. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial."}
• {"criterion_text":"- 27. 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."}
• {"criterion_text":"- 28. Participant is under legal guardianship."}
• {"criterion_text":"- 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)."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 5. Received potentially curative radiation therapy to the lung that is > 30 Gy within 6 months prior to the first dose of IMP."}
• {"criterion_text":"- 6. Received or completed any focal radiotherapy for symptoms within 28 days of the first dose of IMP."}
• {"criterion_text":"- 7. Expected to require any other form of antineoplastic therapy while on trial."}
• {"criterion_text":"- 8. Received a live or live-attenuated vaccination within 30 days of planned treatment start."}
• {"criterion_text":"- 9. Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction."}

Primary endpoints

• {"endpoint_text":"- Objective response rate (ORR), defined as the 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","definition_or_measurement_approach":"ORR defined as percentage of participants with BOR of CR or PR per RECIST v1.1 assessed by Investigator at any time during the core trial period."}

Secondary endpoints

• {"endpoint_text":"- 1. Incidence, type, and severity of adverse events (AEs), recorded as treatment-emergent (TEAEs), treatment-related AEs (including immune mediated AEs (imAEs) as AEs of Special Interest (AESIs)) and serious AEs (SAEs)","definition_or_measurement_approach":"Recorded incidence, type, severity of AEs categorized as TEAEs, treatment-related AEs (including imAEs/AESIs), and SAEs."}
• {"endpoint_text":"- 2. Complete response (CR) rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- 3. Partial response (PR) rate","definition_or_measurement_approach":""}
• {"endpoint_text":"- 4. Objective response rate (ORR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 5. Time to response (TTR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 6. Duration of response (DOR)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 7. Progression-free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 8. Overall survival (OS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 9. Participant weight course over time","definition_or_measurement_approach":""}
• {"endpoint_text":"- 10. Maximum concentration (Cmax)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 11. Minimum concentration (Cmin)","definition_or_measurement_approach":""}
• {"endpoint_text":"- 12. Participants’ subjective well-being as assessed via the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ)","definition_or_measurement_approach":"Assessed using NSCLC-SAQ patient-reported questionnaire."}
• {"endpoint_text":"- 13. Participants' quality of life as assessed via the 5-day Functional Living Index-Emesis (5-day FLIE), focusing on the impact of chemotherapy-induced nausea and vomiting on daily activities and overall well-being","definition_or_measurement_approach":"Assessed using 5-day FLIE instrument focusing on chemo-induced nausea/vomiting impact on daily activities."}

Germany

Earliest CTIS Part Ii Submission Date

20-05-2025

Latest Decision Or Authorization Date

03-02-2026

Processing Time Days

259

Number Of Sites

6

Number Of Participants

18

Italy

Earliest CTIS Part Ii Submission Date

05-06-2025

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

242

Number Of Sites

7

Number Of Participants

9

Romania

Earliest CTIS Part Ii Submission Date

15-05-2025

Latest Decision Or Authorization Date

03-02-2026

Processing Time Days

264

Number Of Sites

4

Number Of Participants

11

Poland

Earliest CTIS Part Ii Submission Date

09-05-2025

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

269

Number Of Sites

3

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

23-05-2025

Latest Decision Or Authorization Date

02-02-2026

Processing Time Days

255

Number Of Sites

15

Number Of Participants

31

Bulgaria

Earliest CTIS Part Ii Submission Date

04-06-2025

Latest Decision Or Authorization Date

12-06-2025

Processing Time Days

8

Number Of Sites

3

Number Of Participants

7

Primary sponsor

Full Name

CatalYm GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Psi Cro AG

Responsibilities

codes: 1,12,2,5

Third parties

• {"country":"Germany","full_name":"Metronomia Clinical Research GmbH","duties_or_roles":"phone: +4989829265100; email: gdfather@metronomia.net","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Mlm Medical Labs GmbH","duties_or_roles":"Laboratory Kit Supply, Sample Management & Triage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Fisher Clinical Services Inc.","duties_or_roles":"Drug Product: Secondary packaging, Labelling","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Eurofins Adme Bioanalyses","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Solvias France","duties_or_roles":"Drug Product: Stability testing (sterility), Release testing(sterility)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Alderley Analytical Limited","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH","duties_or_roles":"Drug Product: QP Release, Distribution","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Fisher Clinical Services GmbH (additional address)","duties_or_roles":"Decomissioning","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Lonza AG","duties_or_roles":"Drug Substance: Release testing (Polysorbate), Stability testing (Polysorbate); Drug Product: Release testing, Stability testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Lonza Biologics Inc.","duties_or_roles":"Drug Substance: Cell bank storage","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"CluePoints","duties_or_roles":"code: 15","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Bioreliance Limited","duties_or_roles":"Drug Substance: Release testing, Stability testing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Personal Genome Diagnostics Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Lonza Biologics PLC","duties_or_roles":"Drug Substance: cell bank storage, Manufacturing, Primary Packaging, Release testing, Stability testing; Drug Product: Stability testing (potency)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioreliance Corp.","duties_or_roles":"Drug Substance: Release testing, Stability testing","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH (Allschwil)","duties_or_roles":"Drug Product: Secondary packaging, Labelling","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Psi Cro AG","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Lonza AG (Stein Ag address)","duties_or_roles":"Drug Product: Manufacturing, Primary Packaging, Stability testing (microbiologic), Release testing(microbiologic)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Solvias France (additional entry)","duties_or_roles":"Drug Product: Stability testing (sterility), Release testing(sterility)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Fisher Clinical Services GmbH (Steinbuhlweg address)","duties_or_roles":"Drug Product: Secondary packaging, Labelling","organisation_type":"Pharmaceutical company"}