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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CatalYm GmbH

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Jul 2025 → ongoing

Decision date (initial)

2025-06-12

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

CatalYm GmbH

External identifiers

EU CT number

2024-516792-32-01

WHO UTN

U1111-1312-1131

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy, Therapy

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

Secondary objectives 5

1. 1. To investigate the safety and tolerability of visugromab plus ICT versus placebo plus ICT
2. 2. To investigate additional efficacy parameters in participants treated with visugromab plus ICT versus placebo plus ICT
3. 3. To investigate pharmacokinetics (PK) of visugromab in peripheral blood in participants treated with visugromab plus ICT
4. 4. To evaluate changes in health-related quality-of-life (HR-QoL) from baseline in participants treated with the combination of visugromab plus ICT versus placebo plus ICT
5. 5. To assess the impact of chemotherapy-induced nausea and vomiting on participants’ daily lives, focusing on the frequency and severity of these symptoms

Conditions and MedDRA coding

Metastatic non-squamous non-small cell lung cancer

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. 1. Histologically confirmed, newly diagnosed stage IV non-squamous NSCLC
2. 2. Demonstrated absence of actionable mutations (e.g. EGFR, ALK, among others) that suggest/require treatment with an available targeted agent.
3. 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. 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. 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. 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. 7. Age ≥ 18 years on the day of signing the informed consent.
8. 8. Life expectancy of at least 3 months as assessed by the Investigator.
9. 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
10. 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. 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. 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. 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. 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).

Exclusion criteria 28

1. 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).
2. 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.
3. 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. 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. 5. Received potentially curative radiation therapy to the lung that is > 30 Gy within 6 months prior to the first dose of IMP.
6. 6. Received or completed any focal radiotherapy for symptoms within 28 days of the first dose of IMP.
7. 7. Expected to require any other form of antineoplastic therapy while on trial.
8. 8. Received a live or live-attenuated vaccination within 30 days of planned treatment start.
9. 9. Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction.
10. 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.
11. 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. 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. 13. Prior severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
14. 14. Known sensitivity to any component of pembrolizumab, or pemetrexed, or carboplatin.
15. 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. 16. Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes.
17. 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.
18. 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. 19. Unable or unwilling to take folic acid or vitamin B12 supplementation.
20. 20. Presence of active infection requiring systemic therapy.
21. 21. Known history of Human Immunodeficiency Virus (HIV; known HIV 1/2 antibody [Ab] positive).
22. 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. 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. 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. 25. Interstitial lung disease or a history of non-infectious pneumonitis that required systemic steroids or current pneumonitis.
26. 26. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.
27. 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.
28. 28. Participant is under legal guardianship.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 13

1. 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)
2. 2. Complete response (CR) rate
3. 3. Partial response (PR) rate
4. 4. Objective response rate (ORR)
5. 5. Time to response (TTR)
6. 6. Duration of response (DOR)
7. 7. Progression-free survival (PFS)
8. 8. Overall survival (OS)
9. 9. Participant weight course over time
10. 10. Maximum concentration (Cmax)
11. 11. Minimum concentration (Cmin)
12. 12. Participants’ subjective well-being as assessed via the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ)
13. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CatalYm GmbH

Sponsor organisation

CatalYm GmbH

Address

Am Klopferspitz 19, Martinsried Martinsried

City

Planegg

Postcode

82152

Country

Germany

Scientific contact point

Organisation

CatalYm GmbH

Contact name

Medical Lead

Public contact point

Organisation

CatalYm GmbH

Contact name

Regulatory Affairs

Third parties 23

Locations

6 EU/EEA countries · 37 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications