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

Phase 1

Active, not recruiting

• Conditions: Solid Tumor, Adult

• Registration Number: NCT04725474
• Lead Sponsor: CatalYm GmbH

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-12-09
• Study First Submitted: 2021-01-14
• Study First Submitted QC: 2021-01-25
• Study First Posted: 2021-01-26
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-07
• Last Update Posted: 2024-08-09
• Primary Completion: 2025-10-31
• Study Completion: 2027-10-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 274

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (13)

Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik und Poliklinik; 🇩🇪 Essen, Germany

Universitätsklinikum Frankfurt, Medizinische Klinik I; 🇩🇪 Frankfurt am Main, Germany

Universitätsklinikum Würzburg, Comprehensive Cancer Center; 🇩🇪 Würzburg, Germany

Next Oncology, Phase I Unit. IOB - Hospital Quironsalud; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall d'Hebron, Institute of Oncology; 🇪🇸 Barcelona, Spain

ICMDiM, Hospital Clinic; 🇪🇸 Barcelona, Spain

ICO Hospitalet, Hospital Duran i Reynals; 🇪🇸 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, Spain

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