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.

Enrolment into the Ph 2 part is completed.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 199
• 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.
• Histologically or cytologically confirmed/documented diagnosis of advanced-stage, relapsed/refractory solid tumors in non-curable state as per current clinical knowledge (specific for Germany: who have exhausted all available approved standard treatments) or are not eligible for them anymore).
• Part A: At least one anti-PD-1/PD-L1 treatment (alone or in combination) and progressed on or relapsed after completion of the anti-PD-1/PD-L1 treatment (with a minimum of 12 weeks of anti-PD1/PD-L1 exposure).
• Part B: (1) bladder cancer, hepatocellular cancer, non-small cell lung cancer or melanoma (cutaneous and mucosal forms, not uveal/ocular) that relapsed on or were primary refractory to prior anti-PD-1/PD-L1 therapy with an approved anti-PD-1/PD-L1 compound (with a minimum of 12 weeks of anti-PD-1/PD-L1 exposure; specific for Germany: and have exhausted all available approved standard treatments or are not eligible for them anymore); (2) colorectal cancer (MSS/mismatch-repair competent) and have not received any prior anti-PD-1/PD-L1 therapy (Not applicable in Germany); (3) biomarker cohort with mixed solid tumors ("basket" cohort;) that relapsed on or were primary refractory to prior anti-PD1/PD-L1 therapy with an approved anti-PD-1/PD-L1 compound and that have exhausted available approved therapies for their disease or do not qualify for them anymore (specific for Germany: and have exhausted all available approved standard treatments or are not eligible for them anymore).
• 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/iRECIST (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 disease 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).
• Ongoing immune-related AEs (irAEs) and/or AEs ≥ Grade 2 not resolved from previous therapies except vitiligo, stable peripheral sensory neuropathy up to Grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy.
• History of or clinical evidence of CNS primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, demonstrated no progression at least for 3 months before Screening, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before 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; Biological: nivolumab; 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; Biological: nivolumab; 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 V1.1 (Part B)	RECIST V1.1 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 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
Evaluation of treatment-induced anti-drug antibodies (ADA) (Part A & B)		min. 6 weeks
Evaluation of clinical efficacy according RECIST V1.1 (Part A)	RECIST V1.1 is measured every 6-8 weeks during treatment	min. 6 weeks

Collaborators and Investigators

• Sponsor: CatalYm GmbH
• Investigators: Study Director: Frank Hermann, MD, CatalYm GmbH

Publications and helpful links

General Publications

• Melero I, de Miguel M, Cabanas EG, de Velasco G, Joerger M, Martin-Liberal J, Reig M, Konig D, Trojan J, Goebeler ME, Schuler M, Alonso G, Dummer R, Rodriguez-Ruiz ME, Yarza R, Pretelli G, Esteban-Villarubia J, Koster KL, Viltro PS, Sanduzzi-Zamparelli M, Laubli H, Koch C, Sayehli C, Gromke T, Racca F, Ramelyte E, Galle PR, Necchi A, Reck M, Trajanoski Z, Hackl H, Gogolla F, Billing J, Sattmann T, Wischhusen J, Schuberth-Wagner C, Akdemir J, Lichtenegger FS, Auckenthaler A, Fox M, Klar K, Fettes P, Liebig M, Amin A, Sachdeva S, Hermann F, Leo E. Long-term follow-up of a phase 1/2 trial of anti-GDF-15 antibody visugromab plus anti-PD-1 antibody nivolumab in anti-PD-1/-L1 relapsed/refractory solid tumors. J Hematol Oncol. 2026 Jul 9. doi: 10.1186/s13045-026-01818-2. Online ahead of print.

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 (Actual): August 19, 2026
• Last Update Submitted That Met QC Criteria: August 17, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: CTL-002; GDF-15; visugromab
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab
• 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