First-in-Human Study of the GDF-15 Neutralizing Antibody... | NCT04725474

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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)
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)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
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

Outcomes Module

Primary Outcomes

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 (Part B)	RECIST is measured every 6-8 weeks treatment	min. 6 weeks

Secondary Outcomes

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

Eligibility Module

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
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).