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

NCT04725474 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CTL-002-001
• Study Type: interventional
• Target: 199
• Locations: 3 countries
• Sites: 13

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. Enrolment into the Ph 2 part is completed.

Conditions

Solid Tumor, Adult

Keywords

CTL-002; GDF-15; visugromab

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (9)

• Cmax following the first dose of CTL-002 (Part A & B)

  1 day

• AUC following the first dose of CTL-002 (Part A & B)

  14 days

• Half-life of CTL-002 (Part A & B)

  min. 6 weeks

• Evaluation of treatment-emergent cytokine/chemokine concentrations (Part A & B)

  min. 6 weeks

• Evaluation of treatment-induced anti-drug antibodies (ADA) (Part A & B)

  min. 6 weeks

Study Arms (2)

Phase 1 (Part A; dose escalation): CTL-002 Monotherapy + Checkpoint Inhibitor Combination

EXPERIMENTAL

Up to 5 dose levels with visugromab (CTL-002) administered as IV monotherapy and in combination with a CPI

Biological: visugromab (CTL-002); Biological: nivolumab

Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination

EXPERIMENTAL

At defined dose level(s) with visugromab (CTL-002)

Biological: visugromab (CTL-002); Biological: nivolumab

Interventions

visugromab (CTL-002) BIOLOGICAL

monoclonal antibody

Phase 1 (Part A; dose escalation): CTL-002 Monotherapy + Checkpoint Inhibitor Combination; Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination

nivolumab BIOLOGICAL

monoclonal antibody

Phase 1 (Part A; dose escalation): CTL-002 Monotherapy + Checkpoint Inhibitor Combination; Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• CatalYm GmbH: lead

Study Sites (13)

Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik und Poliklinik

Essen, 45147, Germany

Location

Universitätsklinikum Frankfurt, Medizinische Klinik I

Frankfurt am Main, 60590, Germany

Location

Universitätsklinikum Würzburg, Comprehensive Cancer Center

Würzburg, 97078, Germany

Location

Next Oncology, Phase I Unit. IOB - Hospital Quironsalud

Barcelona, 08023, Spain

Location

Hospital Universitari Vall d'Hebron, Institute of Oncology

Barcelona, 08035, Spain

Location

ICMDiM, Hospital Clinic

Barcelona, 08036, Spain

Location

ICO Hospitalet, Hospital Duran i Reynals

Barcelona, 08908, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

START Madrid, Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Clinica Universidad de Navarra, Unidad Central de Ensayos Clinicos

Pamplona, 31008, Spain

Location

University Hospital Basel, Department for Medical Oncology

Basel, 4031, Switzerland

Location

Kantonsspital St. Gallen, Clinic for Medical Oncology & Hematology

Sankt Gallen, 9007, Switzerland

Location

University Hospital Zurich, Department of Dermatology

Zurich, 9091, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 42426863 DERIVED

MeSH Terms

Interventions

Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Frank Hermann, MD

  CatalYm GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: January 26, 2021
• Study Start: December 9, 2020
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2030
• Last Updated: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); CH (3); ES (7)