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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
107
Participants receive Visugromab (recommended dose) intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
Participants receive Matching Placebo intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
Participants receive Pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments after visugromab infusion.
Participants receive Pemetrexed 500 mg/m\^2 IV on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.
Participants receive Carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) on Day 1 of each 21-day cycle for four cycles.
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGUSC Norris Comprehensive Cancer Center
Los Angeles, California, United States
RECRUITINGYale Cancer Center
New Haven, Connecticut, United States
RECRUITINGMoffitt Cancer Center
Tampa, Florida, United States
Objective Response Rate
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
Time frame: up to 24 months
Adverse Events
Incidence, type and severity of adverse events, treatment emergent adverse events, treatment-related adverse events and serious adverse events
Time frame: up to 27 months
CR rate
Complete response rate
Time frame: up to 24 months
PR rate
Partial response rate
Time frame: up to 24 months
DOR
Duration of response
Time frame: up to 24 months
ORR
Objective response rate
Time frame: up to 24 months
TTR
Time-to-response rate
Time frame: up to 24 months
PFS
Progression-free survival
Time frame: up to 48 months
OS
Overall survival
Time frame: up to 48 months
Participant weight course over time
Time frame: up to 48 months
Maximum Concentration (Cmax) of visugromab
Cmax is the maximum observed serum concentration of visugromab
Time frame: At designated time points (up to 24 months)
Minimum Concentration (Cmin) of visugromab
Cmin is the minimum observed serum concentration of visugromab
Time frame: At designated time points (up to 24 months)
Participants' subjective well-being as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)
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.
Time frame: up to 27 months
Participants' quality of life as assessed by 5-day Functional Living Index-Emesis (5-day FLIE)
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.
Time frame: At designated time points (up to 3 months)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
NYU Longone Health
New York, New York, United States
RECRUITINGDuke University Medical Center
Durham, North Carolina, United States
RECRUITINGMedical University of South Carolina
Charleston, South Carolina, United States
RECRUITINGThorax Clinic Heidelberg
Heidelberg, Baden-Wurttemberg, Germany
RECRUITINGUniversity Hospital Würzburg
Würzburg, Bavaria, Germany
RECRUITINGEvangelical Hospital Bethel, Clinic for Internal Medicine, Hematology/Oncology, Palliative Medicine Johannesstift
Bielefeld, North Rhine-Westphalia, Germany
RECRUITING...and 32 more locations