A Phase I/II, 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)
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Study Summary
To evaluate CTL 002 in cancer.
To Determine the recommended phase 2 dose (RP2D) and further evaluate safety and preliminary efficacy of CTL-002 monotherapy and the combination.
Main endpoints are safety of CTL-002 monotherapy and CTL-002 combination with an anti-PD-1 antibody, pharmacokinetics, pharmacodynamics (e.g. degree of GDF-15 neutralization achieved and change in immune-cell number and composition in the tumor tissue) as well as preliminary clinical efficacy (tumor mass reduction; anticachexia effect).
Biomarker and response assessments will be reported.
To assess the prediction accuracy of response for two potential biomarkers in a total of 25 cancer patients treated with the GDF-15-targeting antibody visugromab in combination with the anti-PD1 antibody nivolumab in patients that are relapsed/refractory to prior anti-PD1/PD-L1 treatment.
To explore the preliminary anti-tumor activity of CTL-002 administered in combination with an anti-PD-1 checkpoint inhibitor in in subjects with advanced-stage relapsed/refractory solid tumors in non-curable state as per current clinical knowledge that have either (1) bladder cancer, hepatocellular cancer, non-small cell lung cancer or melanoma (for melanoma, only cutaneous and mucosal forms, not uveal/ocular) (approved anti-PD-1/PD-L1 indications) that relapsed on or were primary refractory to prior anti-PD-1/PD-L1 therapy or (2) colorectal cancer (micro-satellite stable [MSS]/mismatch-repair competent) and have not received any prior anti-PD-1/PD-L1 therapy, or (3) mixed solid tumors (“basket” cohort) with tumors that are demonstrated to be PD-L1+ (Tumor Proportion Score [TPS] > 1) at baseline and are relapsed on or were primary refractory to prior anti-PD-1/PD-L1 therapy.
To evaluate Visugromab in combination with an anti-PD1 antibody in patients with advanced solid tumors that are relapsed/refractory to prior anti-PD1/-PD-L1 treatment.
To investigate the treatment of advanced stage cancer patients that are relapsed/refractory to prior anti-PD-1/-PD-L1 treatment with the GDF-15 neutralizing antibody, visugromab, in combination with the anti-PD-1 checkpoint inhibitor nivulomab.
- 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).
- 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).
Clinical Study Information for Healthcare Providers
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