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

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).

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Biological: visugromab (CTL-002)

• Study Type: Interventional
• Enrollment (Actual): 263
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Essen, Germany, 45147
    • Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik und Poliklinik
  • Frankfurt am Main, Germany, 60590
    • Universitätsklinikum Frankfurt, Medizinische Klinik I
  • Würzburg, Germany, 97078
    • Universitätsklinikum Würzburg, Comprehensive Cancer Center
• Spain
  • Barcelona, Spain, 08908
    • ICO Hospitalet, Hospital Duran i Reynals
  • Barcelona, Spain, 08023
    • Next Oncology, Phase I Unit. IOB - Hospital Quironsalud
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron, Institute of Oncology
  • Barcelona, Spain, 08036
    • ICMDiM, Hospital Clinic
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28050
    • START Madrid, Hospital Universitario HM Sanchinarro
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra, Unidad Central de Ensayos Clinicos
• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel, Department for Medical Oncology
  • Sankt Gallen, Switzerland, 9007
    • Kantonsspital St. Gallen, Clinic for Medical Oncology & Hematology
  • Zurich, Switzerland, 9091
    • University Hospital Zurich, Department of Dermatology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 (Part A; dose escalation): CTL-002 Monotherapy + Checkpoint Inhibitor Combination; Up to 5 dose levels with visugromab (CTL-002) administered as IV monotherapy and in combination with a CPI	Biological: visugromab (CTL-002); monoclonal antibody
Experimental: Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination; At defined dose level(s) with visugromab (CTL-002)	Biological: visugromab (CTL-002); monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (Parts A & B)	Incidence of treatment emergent adverse events in monotherapy and/or combination therapy	min. 2 months
Determination of DLT and MTD (Part A)	Assessment of toxicities in monotherapy and/or combination therapy per dose level	28 days
Evaluation of clinical efficacy according RECIST (Part B)	RECIST is measured every 6-8 weeks treatment	min. 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax following the first dose of CTL-002 (Part A & B)	PK parameter from serum CTL-002 levels	1 day
AUC following the first dose of CTL-002 (Part A & B)	PK parameter from serum CTL-002 levels	14 days
Half-life of CTL-002 (Part A & B)	PK parameter from serum CTL-002 levels	min. 6 weeks
Evaluation of clinical efficacy according RECIST (Part A)	RECIST is measured every 6-8 weeks during treatment	min. 6 weeks
Evaluation of appetite (Part A)	Assessment of appetite via quality of life questionnaire	min. 6 weeks
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
Evaluation of treatment-emergent cytokine/chemokine concentrations (Part A & B)	Measurement of concentration in peripheral blood	min. 6 weeks
Assessment of lumbar vertebra skeletal muscle index (L3SMI) (cm2/m2) (Parts A & B)	Combining measurement of L3 vertebra skeletal muscle mass via computed tomography (CT) in cm2 and patient height (squared) in m2	min. 6 weeks

Collaborators and Investigators

• Sponsor: CatalYm GmbH
• Investigators: Study Director: Sujata Rao, MD, CatylYm GmbH

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2030

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: January 25, 2021
• First Posted (Actual): January 26, 2021

Study Record Updates

• Last Update Posted (Estimated): January 12, 2026
• Last Update Submitted That Met QC Criteria: January 9, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: CTL-002; GDF-15; visugromab
• Other Study ID Numbers: CTL-002-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No