First-in-Human Study of the GDF-15 Neutralizing Antibody Visugromab (CTL-002) in Patients With Advanced Cancer (GDFATHER)
- Conditions
- Solid Tumor, Adult
- Interventions
- Biological: visugromab (CTL-002)
- Registration Number
- NCT04725474
- Lead Sponsor
- CatalYm GmbH
- Brief Summary
The Phase 1 part (Part A) is a dose escalation study of IV visugromab (CTL-002, a monoclonal antibody neutralizing GDF-15) as monotherapy and in combination with an approved checkpoint inhibitor (CPI) in patients with advanced solid tumors.
Enrolment into the Ph 1 part is completed.
The Phase 2 parts (Part B) are cohort expansions with visugromab (CTL-002) in combination with a defined CPI at a fixed dose into seven different solid tumor indications.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 274
- Signed and dated informed consent, and able to comply with the study procedures and any locally required authorization.
- Male or female aged ≥ 18 years.
- Relapsed/refractory patients with histologically or cytologically confirmed diagnosis of advanced-stage or recurrent cancer (Germany-specific: and have exhausted all standard of care treatments or are not eligible for such treatments)
- Progressed on/relapsed after at least one prior anti-PD-1/PD-L1 treatment
- Biopsy-accessible tumor lesions and willing to undergo triple sequential tumor biopsy (Part A) and dual biopsy (Part B, only for selected cohorts).
- At least 1 radiologically measurable lesion per RECIST V1.1/imRECIST (Part B).
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Life expectancy > 3 months as assessed by the Investigator.
- Adequate organ function (bone marrow, hepatic, renal function and coagulation).
Main
- Pregnant or breastfeeding.
- Any tumor-directed therapy within 21 days before study treatment.
- Treatment with investigational agent within 21 days before study treatment.
- Radiotherapy within 14 days before study treatment.
- Pre-existing arrhythmia, uncontrolled angina pectoris, uncontrolled heart failure (NYHA) Grade IV, any myocardial infarction/coronary event, CNS-ischemic event and any thromboembolic event at any time < 6 months prior to Screening or presence of any uncontrolled heart failure NYHA Grade III or higher.
- Left ventricular ejection fraction (LVEF) < 50% measured by echocardiogram or MUGA.
- QTcF > 450 ms for men or > 470 ms for women.
- Any active autoimmune requiring systemic immunosuppressive treatments. .
- Any history of non-infectious pneumonitis < 6 months prior to Screening.
- Any active inflammatory bowel disease such as Crohn's disease or ulcerative colitis which are generally excluded or active autoimmunthyroiditis present < 6 months prior to Screening.
- History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (< 6 months prior to Screening).
- Evidence for active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), tuberculosis (TB), or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination visugromab (CTL-002) At defined dose level(s) with visugromab (CTL-002) Phase 1 (Part A; dose escalation): CTL-002 Monotherapy + Checkpoint Inhibitor Combination visugromab (CTL-002) Up to 5 dose levels with visugromab (CTL-002) administered as IV monotherapy and in combination with a CPI
- Primary Outcome Measures
Name Time Method Determination of DLT and MTD (Part A) 28 days Assessment of toxicities in monotherapy and/or combination therapy per dose level
Evaluation of clinical efficacy according RECIST (Part B) min. 6 weeks RECIST is measured every 6-8 weeks treatment
Adverse Events (Parts A & B) min. 2 months Incidence of treatment emergent adverse events in monotherapy and/or combination therapy
- Secondary Outcome Measures
Name Time Method Half-life of CTL-002 (Part A & B) min. 6 weeks PK parameter from serum CTL-002 levels
Assessment of Body-Mass-Index (BMI) (kg/m2) (Part A) min. 6 weeks Calculation of BMI in kg/m2 by combining measurement of body weight in kg and body height in cm
Cmax following the first dose of CTL-002 (Part A & B) 1 day PK parameter from serum CTL-002 levels
AUC following the first dose of CTL-002 (Part A & B) 14 days PK parameter from serum CTL-002 levels
Evaluation of appetite (Part A) min. 6 weeks Assessment of appetite via quality of life questionnaire
Evaluation of treatment-emergent cytokine/chemokine concentrations (Part A & B) min. 6 weeks Measurement of concentration in peripheral blood
Evaluation of clinical efficacy according RECIST (Part A) min. 6 weeks RECIST is measured every 6-8 weeks during treatment
Assessment of lumbar vertebra skeletal muscle index (L3SMI) (cm2/m2) (Part A) min. 6 weeks Combining measurement of L3 vertebra skeletal muscle mass via computed tomography (CT) in cm2 and patient height (squared) in m2
Trial Locations
- Locations (13)
Universitätsklinikum Frankfurt, Medizinische Klinik I
🇩🇪Frankfurt am Main, Germany
Next Oncology, Phase I Unit. IOB - Hospital Quironsalud
🇪🇸Barcelona, Spain
University Hospital Zurich, Department of Dermatology
🇨🇭Zurich, Switzerland
Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik und Poliklinik
🇩🇪Essen, Germany
ICO Hospitalet, Hospital Duran i Reynals
🇪🇸Barcelona, Spain
Clinica Universidad de Navarra, Unidad Central de Ensayos Clinicos
🇪🇸Pamplona, Spain
START Madrid, Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Kantonsspital St. Gallen, Clinic for Medical Oncology & Hematology
🇨🇭Saint Gallen, Switzerland
Universitätsklinikum Würzburg, Comprehensive Cancer Center
🇩🇪Würzburg, Germany
Hospital Universitari Vall d'Hebron, Institute of Oncology
🇪🇸Barcelona, Spain
ICMDiM, Hospital Clinic
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
University Hospital Basel, Department for Medical Oncology
🇨🇭Basel, Switzerland