Clinical trial NCT04725474: First-in-Human Study of the GDF-15 Neutralizing Antibody Visugromab (CTL-002) in Patients With Advanced Cancer (GDFATHER)
Official title: A Phase 1/2, FIH, Two-part, Open-label Clinical Trial of Intravenous (IV) Administration of CTL-002 Given as Monotherapy and/or in Combination With an Anti-PD-1 Checkpoint Inhibitor in Subjects With Advanced-stage, Relapsed/Refractory Solid Tumors (The "GDFATHER"-Trial: GDF-15 Antibody-mediaTed Human Effector Cell Relocation).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Keywords: CTL-002
GDF-15
visugromab
Lead sponsor: CatalYm GmbH
Sponsor class: INDUSTRY
First posted: 2021-01-26
Enrollment: 274
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients will be assigned to a dose level of CTL-002 (Part A) or an expansion cohort (Part B) at the time of their enrollment
Primary purpose: TREATMENT

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.


Eligibility criteria: Main Inclusion Criteria:

* 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 Exclusion Criteria:

* 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).

Primary outcomes:
measure: Adverse Events (Parts A & B)
timeFrame: min. 2 months
measure: Determination of DLT and MTD (Part A)
timeFrame: 28 days
measure: Evaluation of clinical efficacy according RECIST (Part B)
timeFrame: min. 6 weeks
Secondary outcomes:
measure: Cmax following the first dose of CTL-002 (Part A & B)
timeFrame: 1 day
measure: AUC following the first dose of CTL-002 (Part A & B)
timeFrame: 14 days
measure: Half-life of CTL-002 (Part A & B)
timeFrame: min. 6 weeks
measure: Evaluation of treatment-emergent cytokine/chemokine concentrations (Part A & B)
timeFrame: min. 6 weeks
measure: Evaluation of clinical efficacy according RECIST (Part A)
timeFrame: min. 6 weeks
measure: Evaluation of appetite (Part A)
timeFrame: min. 6 weeks
measure: Assessment of Body-Mass-Index (BMI) (kg/m2) (Part A)
timeFrame: min. 6 weeks
measure: Assessment of lumbar vertebra skeletal muscle index (L3SMI) (cm2/m2) (Part A)
timeFrame: min. 6 weeks
Other outcomes:
Locations:
city: Essen
country: Germany
facility: Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik und Poliklinik
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt, Medizinische Klinik I
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg, Comprehensive Cancer Center
city: Barcelona
country: Spain
facility: Next Oncology, Phase I Unit. IOB - Hospital Quironsalud
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron, Institute of Oncology
city: Barcelona
country: Spain
facility: ICMDiM, Hospital Clinic
city: Barcelona
country: Spain
facility: ICO Hospitalet, Hospital Duran i Reynals
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: START Madrid, Hospital Universitario HM Sanchinarro
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra, Unidad Central de Ensayos Clinicos
city: Basel
country: Switzerland
facility: University Hospital Basel, Department for Medical Oncology
city: Saint Gallen
country: Switzerland
facility: Kantonsspital St. Gallen, Clinic for Medical Oncology & Hematology
city: Zurich
country: Switzerland
facility: University Hospital Zurich, Department of Dermatology
Study officials:
affiliation: CatylYm GmbH
name: Eugen Leo, MD, PhD, MBA
role: STUDY_DIRECTOR
References: