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

Sponsor
CatalYm GmbH (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04725474
Collaborator
(none)
155
Enrollment
6
Locations
2
Arms
53.7
Anticipated Duration (Months)
25.8
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The Phase 1 part (Part A) is a dose escalation study of IV CTL002 (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 CTL-002 in combination with a defined CPI at a fixed dose into currently six different solid tumor indications.

Condition or Disease Intervention/Treatment Phase
  • Biological: CTL-002
 Phase 1/Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
155 participants
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 enrollmentPatients 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
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).
Actual Study Start Date :
Dec 9, 2020
Anticipated Primary Completion Date :
May 31, 2023
Anticipated Study Completion Date :
May 31, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Phase 1 (Part A; dose escalation): CTL-002 Monotherapy + Checkpoint Inhibitor Combination

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

Biological: CTL-002
monoclonal antibody
Experimental: Phase 2 (Part B; expansion): CTL-002 + Checkpoint Inhibitor Combination

At defined dose level(s) with CTL-002

Biological: CTL-002
monoclonal antibody

Outcome Measures

Primary Outcome Measures

  1. Adverse Events (Parts A & B) [min. 2 months]

    Incidence of treatment emergent adverse events in monotherapy and/or combination therapy

  2. Determination of DLT and MTD (Part A) [28 days]

    Assessment of toxicities in monotherapy and/or combination therapy per dose level

  3. Evaluation of clinical efficacy according RECIST (Part B) [min. 6 weeks]

    RECIST is measured every 6-8 weeks treatment

Secondary Outcome Measures

  1. Cmax following the first dose of CTL-002 (Part A & B) [1 day]

    PK parameter from serum CTL-002 levels

  2. AUC following the first dose of CTL-002 (Part A & B) [14 days]

    PK parameter from serum CTL-002 levels

  3. Half-life of CTL-002 (Part A & B) [min. 6 weeks]

    PK parameter from serum CTL-002 levels

  4. Evaluation of treatment-emergent cytokine/chemokine concentrations (including TNF-a, IFN-g, IL-2, CXCL-9 and CXCL-10) (Part A & B) [min. 6 weeks]

    Measurement of concentration in peripheral blood

  5. Evaluation of clinical efficacy according RECIST (Part A) [min. 6 weeks]

    RECIST is measured every 6-8 weeks during treatment

  6. Evaluation of appetite (Part A) [min. 6 weeks]

    Assessment of appetite via quality of life questionnaire

  7. 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

  8. 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  • 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).

Contacts and Locations

Locations

Site City State Country Postal Code
1 Universitätsklinikum Essen, Westdeutsches Tumorzentrum, Innere Klinik und Poliklinik Essen Germany 45147
2 Universitätsklinikum Würzburg, Comprehensive Cancer Center Würzburg Germany 97078
3 Hospital Universitari Vall d'Hebron, Institute of Oncology Barcelona Spain 08035
4 START Madrid, Hospital Universitario HM Sanchinarro Madrid Spain 28050
5 Clinica Universidad de Navarra, Unidad Central de Ensayos Clinicos Pamplona Spain 31008
6 University Hospital Zurich, Department of Dermatology Zurich Switzerland 9091

Sponsors and Collaborators

  • CatalYm GmbH

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
CatalYm GmbH
ClinicalTrials.gov Identifier:
NCT04725474
Other Study ID Numbers:
  • CTL-002-001
First Posted:
Jan 26, 2021
Last Update Posted:
Mar 17, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by CatalYm GmbH
CTL-002
GDF-15

Study Results

No Results Posted as of Mar 17, 2022