First-in-Human Study of the GDF-15 Neutralizing Antibody Visugromab (CTL-002) in Patients With Advanced Cancer (GDFATHER)

Solid Tumor, Adult Clinical Trial

— 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).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04725474
• Other study ID #: CTL-002-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 9, 2020
• Est. completion date: October 31, 2027

Study information

• Verified date: July 2023
• Source: CatalYm GmbH
• Contact: Eugen Leo, MD, PhD, MBA / CMO
• Phone: +49 89 200066440
• Email: eugen.leo[@]catalym.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 274
• Est. completion date: October 31, 2027
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 (Part A)
• 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).

Related Conditions & MeSH terms

• Solid Tumor, Adult

Intervention

Biological:
• visugromab (CTL-002)
monoclonal antibody

Locations

Country	Name	City	State
Germany	Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik und Poliklinik	Essen
Germany	Universitätsklinikum Würzburg, Comprehensive Cancer Center	Würzburg
Spain	Hospital Universitari Vall d'Hebron, Institute of Oncology	Barcelona
Spain	ICO Hospitalet, Hospital Duran i Reynals	Barcelona
Spain	Next Oncology, Phase I Unit. IOB - Hospital Quironsalud	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	START Madrid, Hospital Universitario HM Sanchinarro	Madrid
Spain	Clinica Universidad de Navarra, Unidad Central de Ensayos Clinicos	Pamplona
Switzerland	University Hospital Basel, Department for Medical Oncology	Basel
Switzerland	Kantonsspital St. Gallen, Clinic for Medical Oncology & Hematology	Saint Gallen
Switzerland	University Hospital Zurich, Department of Dermatology	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
CatalYm GmbH

Countries where clinical trial is conducted

Germany,  Spain,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse Events (Parts A & B)	Incidence of treatment emergent adverse events in monotherapy and/or combination therapy	min. 2 months
Primary	Determination of DLT and MTD (Part A)	Assessment of toxicities in monotherapy and/or combination therapy per dose level	28 days
Primary	Evaluation of clinical efficacy according RECIST (Part B)	RECIST is measured every 6-8 weeks treatment	min. 6 weeks
Secondary	Cmax following the first dose of CTL-002 (Part A & B)	PK parameter from serum CTL-002 levels	1 day
Secondary	AUC following the first dose of CTL-002 (Part A & B)	PK parameter from serum CTL-002 levels	14 days
Secondary	Half-life of CTL-002 (Part A & B)	PK parameter from serum CTL-002 levels	min. 6 weeks
Secondary	Evaluation of treatment-emergent cytokine/chemokine concentrations (Part A & B)	Measurement of concentration in peripheral blood	min. 6 weeks
Secondary	Evaluation of clinical efficacy according RECIST (Part A)	RECIST is measured every 6-8 weeks during treatment	min. 6 weeks
Secondary	Evaluation of appetite (Part A)	Assessment of appetite via quality of life questionnaire	min. 6 weeks
Secondary	Assessment of Body-Mass-Index (BMI) (kg/m2) (Part A)	Calculation of BMI in kg/m2 by combining measurement of body weight in kg and body height in cm	min. 6 weeks
Secondary	Assessment of lumbar vertebra skeletal muscle index (L3SMI) (cm2/m2) (Part A)	Combining measurement of L3 vertebra skeletal muscle mass via computed tomography (CT) in cm2 and patient height (squared) in m2	min. 6 weeks