Solid Tumor, Adult
Conditions
Keywords
CTL-002, GDF-15, visugromab
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. Enrolment into the Ph 2 part is completed.
Interventions
BIOLOGICALvisugromab (CTL-002)
monoclonal antibody
BIOLOGICALnivolumab
monoclonal antibody
Sponsors
CatalYm GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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. * Histologically or cytologically confirmed/documented diagnosis of advanced-stage, relapsed/refractory solid tumors in non-curable state as per current clinical knowledge (specific for Germany: who have exhausted all available approved standard treatments) or are not eligible for them anymore). * Part A: At least one anti-PD-1/PD-L1 treatment (alone or in combination) and progressed on or relapsed after completion of the anti-PD-1/PD-L1 treatment (with a minimum of 12 weeks of anti-PD1/PD-L1 exposure). * Part B: (1) bladder cancer, hepatocellular cancer, non-small cell lung cancer or melanoma (cutaneous and mucosal forms, not uveal/ocular) that relapsed on or were primary refractory to prior anti-PD-1/PD-L1 therapy with an approved anti-PD-1/PD-L1 compound (with a minimum of 12 weeks of anti-PD-1/PD-L1 exposure; specific for Germany: and have exhausted all available approved standard treatments or are not eligible for them anymore); (2) colorectal cancer (MSS/mismatch-repair competent) and have not received any prior anti-PD-1/PD-L1 therapy (Not applicable in Germany); (3) biomarker cohort with mixed solid tumors ("basket" cohort;) that relapsed on or were primary refractory to prior anti-PD1/PD-L1 therapy with an approved anti-PD-1/PD-L1 compound and that have exhausted available approved therapies for their disease or do not qualify for them anymore (specific for Germany: and have exhausted all available approved standard treatments or are not eligible for them anymore). * 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/iRECIST (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 disease 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). * Ongoing immune-related AEs (irAEs) and/or AEs ≥ Grade 2 not resolved from previous therapies except vitiligo, stable peripheral sensory neuropathy up to Grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy. * History of or clinical evidence of CNS primary tumors or metastases including leptomeningeal metastases, unless they have been previously treated, demonstrated no progression at least for 3 months before Screening, are asymptomatic and have had no requirement for steroids or enzyme inducing anticonvulsants in the last 14 days before 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (Parts A & B) | min. 2 months | Incidence of treatment emergent adverse events in monotherapy and/or combination therapy |
| 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 V1.1 (Part B) | min. 6 weeks | RECIST V1.1 is measured every 6-8 weeks treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Half-life of CTL-002 (Part A & B) | min. 6 weeks | PK parameter from serum CTL-002 levels |
| Evaluation of treatment-emergent cytokine/chemokine concentrations (Part A & B) | min. 6 weeks | Measurement of concentration in peripheral blood |
| Evaluation of treatment-induced anti-drug antibodies (ADA) (Part A & B) | min. 6 weeks | — |
| Evaluation of clinical efficacy according RECIST V1.1 (Part A) | min. 6 weeks | RECIST V1.1 is measured every 6-8 weeks during treatment |
| Evaluation of appetite (Part A) | min. 6 weeks | Assessment of appetite via quality of life questionnaire |
| 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 |
| Assessment of lumbar vertebra skeletal muscle index (L3SMI) (cm2/m2) (Parts A & B) | min. 6 weeks | Combining measurement of L3 vertebra skeletal muscle mass via computed tomography (CT) in cm2 and patient height (squared) in m2 |
Countries
Germany, Spain, Switzerland
Contacts
STUDY_DIRECTORFrank Hermann, MD
CatalYm GmbH
Outcome results
None listed