NCT04725474进行中（未招募）1 期
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).
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- CatalYm GmbH
- 入组人数
- 199
- 试验地点
- 23
- 主要终点
- Determination of DLT and MTD (Part A)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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-
- •Life expectancy > 3 months as assessed by the Investigator.
- •Adequate organ function (bone marrow, hepatic, renal function and coagulation).
排除标准
- •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).
研究组 & 干预措施
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
干预措施: nivolumab (Biological)
Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination
Experimental
At defined dose level(s) with visugromab (CTL-002)
干预措施: nivolumab (Biological)
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
干预措施: visugromab (CTL-002) (Biological)
Phase 2 (Part B; expansion): visugromab (CTL-002) + Checkpoint Inhibitor Combination
Experimental
At defined dose level(s) with visugromab (CTL-002)
干预措施: visugromab (CTL-002) (Biological)
结局指标
主要结局
Determination of DLT and MTD (Part A)
时间窗: 28 days
Assessment of toxicities in monotherapy and/or combination therapy per dose level
Evaluation of clinical efficacy according RECIST (Part B)
时间窗: min. 6 weeks
RECIST is measured every 6-8 weeks treatment
Adverse Events (Parts A & B)
时间窗: min. 2 months
Incidence of treatment emergent adverse events in monotherapy and/or combination therapy
Evaluation of clinical efficacy according RECIST V1.1 (Part B)
时间窗: min. 6 weeks
RECIST V1.1 is measured every 6-8 weeks treatment
次要结局
- 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)
- Cmax following the first dose of CTL-002 (Part A & B)(1 day)
- AUC following the first dose of CTL-002 (Part A & B)(14 days)
- Half-life of CTL-002 (Part A & B)(min. 6 weeks)
- Evaluation of treatment-emergent cytokine/chemokine concentrations (Part A & B)(min. 6 weeks)
- Evaluation of clinical efficacy according RECIST (Part A)(min. 6 weeks)
- Evaluation of appetite (Part A)(min. 6 weeks)
- Assessment of Body-Mass-Index (BMI) (kg/m2) (Part A)(min. 6 weeks)
- Assessment of lumbar vertebra skeletal muscle index (L3SMI) (cm2/m2) (Parts A & B)(min. 6 weeks)
研究者
研究点 (23)
Loading locations...
相似试验
进行中（未招募）
1 期
Safety and Immunogenicity of an Inactivated West Nile Virus Vaccine in Healthy AdultsWest Nile Viral InfectionNCT06745921National Institute of Allergy and Infectious Diseases (NIAID)30
招募中
1 期
Study to Assess Safety and Tolerability of OPN-6602 in Subjects With Relapsed and/or Refractory Multiple MyelomaRelapsed Multiple MyelomaRefractory Multiple MyelomaNCT06433947Opna Bio LLC130
已完成
1 期
Study of VGX-100 Administered Alone and Co-administered With Bevacizumab in Adult Subjects With Advanced Solid TumorsNeoplasmsCancerNCT01514123Circadian Technologies Ltd.43
已完成
2 期
Safety and Immune Response of One Dose of OVX836 at Two Dose Levels, in Comparison to Influvac TetraTM, After Intramuscular Administration in Healthy Subjects Aged 18-65 YearsInfluenzaNCT04192500Osivax300
终止
1 期
Study of Intralesional Administration of MK-4621 (RGT100) in Adult Participants With Advanced or Recurrent Tumors (MK-4621-001/RGT100-001)Advanced Solid TumorsNCT03065023Merck Sharp & Dohme LLC15
相关资讯
CatalYm Initiates Phase 2b Trial of Visugromab in Second-Line Hepatocellular Carcinoma Treatment- CatalYm has dosed the first patient in the GDFATHER-HCC-01 trial, evaluating visugromab combined with nivolumab and lenvatinib for patients with unresectable or metastatic hepatocellular carcinoma who progressed after first-line anti-PD-(L)1 therapy.
- The anti-GDF-15 antibody visugromab demonstrated encouraging anti-tumor activity in earlier trials, with a median duration of response of 21.4 months in advanced-stage, anti-PD-(L)1 relapsed/refractory HCC patients.
- The global Phase 2b study will enroll approximately 104 participants across 40 sites, with progression-free survival as the primary endpoint and potential cachexia mitigation as an exploratory objective.
- This represents CatalYm's third Phase 2b study of visugromab, expanding development into hepatocellular carcinoma following first and second-line NSCLC programs.5 months agoCatalYm Strengthens Leadership Team to Advance Visugromab Through Late-Stage Development- CatalYm appointed four experienced executives to accelerate visugromab's progression into late-stage clinical development following promising Phase 2a results.
- The company's GDFATHER-2 trial demonstrated that visugromab combined with anti-PD-1 inhibitor produced deep and durable responses across multiple solid tumor types with favorable safety.
- CatalYm is advancing visugromab into multiple Phase 2b studies including first-line metastatic NSCLC and cachexia indications based on Nature-published data.
- The leadership changes position the GDF-15-targeting therapy developer for potential regulatory approval and commercial success in oncology and cachexia markets.last yearCatalYm's Visugromab Shows Promise in Enhancing Antibody-Drug Conjugate Efficacy by Blocking GDF-15- New preclinical data reveals that visugromab, CatalYm's GDF-15-neutralizing antibody, significantly enhances the anti-tumor activity of antibody-drug conjugates (ADCs) in multiple solid tumor models.
- Research demonstrates that ADC treatment triggers GDF-15 expression as a potential resistance mechanism, which visugromab effectively counteracts by improving immune cell infiltration and activation in the tumor microenvironment.
- These findings build on CatalYm's previous clinical evidence showing visugromab's ability to induce durable responses in relapsed/refractory solid tumors and mitigate cancer-associated cachexia.last year