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

Not Applicable

Not yet recruiting

• Conditions: Metastatic Non-Squamous Non-Small Cell Lung Cancer; Adult Solid Tumor
• Interventions: Biological: Visugromab; Drug: Matching placebo for visugromab; Biological: Pembrolizumab 200 mg Q3W; Drug: Pemetrexed 500 mg/m^2; Drug: Carboplatin AUC 5

• Registration Number: NCT07098988
• Lead Sponsor: CatalYm GmbH

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).

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-10
• Study First Submitted QC: 2025-07-25
• Last Update Submitted: 2025-07-25
• Study Start: 2025-07-30
• Study First Posted: 2025-08-01
• Last Update Posted: 2025-08-01
• Primary Completion: 2029-03-31
• Study Completion: 2031-03-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 107

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 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 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A	Visugromab	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.
Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A	Pembrolizumab 200 mg Q3W	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.
Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A	Pemetrexed 500 mg/m^2	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.
Visugromab (CTL-002) + Immunochemotherapy Combination (SoC treatment) - Arm A	Carboplatin AUC 5	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.
Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B	Matching placebo for visugromab	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.
Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B	Pembrolizumab 200 mg Q3W	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.
Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B	Pemetrexed 500 mg/m^2	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.
Placebo + Immunochemotherapy Combination (SoC treatment) - Arm B	Carboplatin AUC 5	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.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate	up to 24 months	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 Outcome Measures

Name	Time	Method
Adverse Events	up to 27 months	Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events
CR rate	up to 24 months	Complete response rate
PR rate	up to 24 months	Partial response rate
DOR	up to 24 months	Duration of response
ORR	up to 24 months	Objective response rate
TTR	up to 24 months	Time-to-response rate
PFS	up to 48 months	Progression-free survival
OS	up to 48 months	Overall survival
Participant weight course over time	up to 48 months
Maximum Concentration (Cmax) of visugromab	At designated time points (up to 24 months)	Cmax is the maximum observed serum concentration of visugromab
Minimum Concentration (Cmin) of visugromab	At designated time points (up to 24 months)	Cmin is the minimum observed serum concentration of visugromab
Participants' subjective well-being as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)	up to 27 months	NSCLC-SAQ is a participant reported outcome with seven (7) items assessing five (5) symptom domains of NSCLC: cough, fatigue, pain, dyspnea, and appetite. Each item is scored individually from 0 ("None/Never") to 4 ("Severe/Always"). The total score is calculated by summing domain scores, which are derived as follows: single-item domains (cough, dyspnea, appetite) use the item score; fatigue uses the mean of two items (or one if only one is answered); pain uses the highest score of two items (or one if only one is answered). The total score ranges from 0-20, with higher scores indicating more severe symptoms. If any domain score is missing, a total score is not computed.
Participants' quality of life as assessed by 5-day Functional Living Index-Emesis (5-day FLIE)	At designated time points (up to 3 months)	FLIE consists of 18 items, with 9 items on nausea and 9 items on vomiting. The impact of nausea and vomiting is assessed through their effects on physical and social activities, and emotional well-being. Each item is rated using a visual analog scale (VAS) from 1 to 7 (In some questions, "1" means that nausea or vomiting does not affect the daily life at all, while in other questions, "1" means it affects the daily life a lot). Scoring is calculated per the FLIE Scoring and Administration Manual. Higher scores indicate less impact of nausea and vomiting on daily life. At least 12 of 18 items must be completed to compute the total score.

Trial Locations

Locations (1)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States