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

• ClinicalTrials.gov Identifier: NCT04725474
• Recruitment Status: Recruiting
• First Posted: January 26, 2021
• Last Update Posted: August 1, 2023
• Sponsor: CatalYm GmbH
• Information provided by (Responsible Party): CatalYm GmbH

Tracking Information

• First Submitted Date: January 14, 2021
• First Posted Date: January 26, 2021
• Last Update Posted Date: August 1, 2023
• Actual Study Start Date: December 9, 2020
• Estimated Primary Completion Date: October 31, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2021)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 27, 2023)

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

Original Secondary Outcome Measures (submitted: January 25, 2021)

• Cmax following the first dose of CTL-002 (Part A & B) [ Time Frame: 1 day ]
  PK parameter from serum CTL-002 levels
• AUC following the first dose of CTL-002 (Part A & B) [ Time Frame: 14 days ]
  PK parameter from serum CTL-002 levels
• Half-life of CTL-002 (Part A & B) [ Time Frame: min. 6 weeks ]
  PK parameter from serum CTL-002 levels
• Evaluation of treatment-emergent cytokine/chemokine concentrations (including TNF-a, IFN-g, IL-2, CXCL-9 and CXCL-10) (Part A & B) [ Time Frame: min. 6 weeks ]
  Measurement of concentration in peripheral blood
• Evaluation of clinical efficacy according RECIST (Part A) [ Time Frame: min. 6 weeks ]
  RECIST is measured every 6-8 weeks during treatment
• Evaluation of appetite [ Time Frame: min. 6 weeks ]
  Assessment of appetite via quality of life questionnaire
• Assessment of Body-Mass-Index (BMI) (kg/m2) [ Time Frame: min. 6 weeks ]
  Calculation of BMI in kg/m2 by combining measurement of body weight in kg and body height in cm
• Assessment of lumbar vertebra skeletal muscle index (L3SMI) (cm2/m2) [ Time Frame: min. 6 weeks ]
  Combining measurement of L3 vertebra skeletal muscle mass via computed tomography (CT) in cm2 and patient height (squared) in m2

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-in-Human Study of the GDF-15 Neutralizing Antibody Visugromab (CTL-002) in Patients With Advanced Cancer (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).

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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Solid Tumor, Adult

Intervention

Biological: visugromab (CTL-002)

monoclonal antibody

Study Arms

• 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
  Intervention: Biological: visugromab (CTL-002)
• Experimental: Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination
  At defined dose level(s) with visugromab (CTL-002)
  Intervention: Biological: visugromab (CTL-002)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 27, 2023): 274
• Original Estimated Enrollment (submitted: January 25, 2021): 155
• Estimated Study Completion Date: October 31, 2027
• Estimated Primary Completion Date: October 31, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Eugen Leo, MD, PhD, MBA / CMO; +49 89 200066440; eugen.leo@catalym.com

Contact: Petra Fettes, PhD; +49 89 200066440; petra.fettes@catalym.com

• Listed Location Countries: Germany, Spain, Switzerland

Administrative Information

• NCT Number: NCT04725474
• Other Study ID Numbers: CTL-002-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: CatalYm GmbH
• Original Responsible Party: Same as current
• Current Study Sponsor: CatalYm GmbH
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Eugen Leo, MD, PhD, MBA; CatylYm GmbH

• PRS Account: CatalYm GmbH
• Verification Date: July 2023