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

CatalYm

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Solid Tumor, Adult

Treatments: Biological: visugromab (CTL-002)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04725474

CTL-002-001

Details and patient eligibility

About

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.

Enrollment: 274 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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).

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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274 participants in 2 patient groups

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

Experimental group

Description:

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

Treatment:

Biological: visugromab (CTL-002)

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

Experimental group

Description:

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

Treatment:

Biological: visugromab (CTL-002)