2024-516794-70-00招募中2 期
A Phase 2, Randomized, Blinded, Placebo-Controlled Trial Investigating the Efficacy and Safety of Visugromab plus Nivolumab with or without Docetaxel versus Docetaxel Monotherapy in Second-Line Treatment of Participants with Metastatic Non-Squamous Non-Small Cell Lung Cancer (GDFATHER-NSCLC-02)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- CatalYm GmbH
- 入组人数
- 95
- 试验地点
- 32
- 主要终点
- Objective response rate (ORR), defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator at any time during the Core Trial Period.
研究概览
简要总结
To investigate the antitumoral effect in participants treated with visugromab (at Dose Level I and Dose Level II) and nivolumab with docetaxel versus visugromab at Dose Level II and nivolumab with placebo versus double placebo and docetaxel
研究设计
- 分配方式
- Randomized
- 主要目的
- Randomized Trial Part
- 盲法
- Double (Monitor, Subject, Investigator, Carer)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Histologically or cytologically confirmed diagnosis of stage IV non squamous NSCLC.
- •All toxicities attributable to prior anti-cancer therapy other than alopecia and fatigue must have resolved to Grade 1 (according to National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) or baseline before start of treatment.
- •Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to receiving the first dose of IMP.
- •Females of childbearing potential must be willing to use a highly effective method of contraception from 14 days before the start of IMP and for the course of the trial through 150 days after the last dose of visugromab or nivolumab or through 180 days after last dose of chemotherapeutic agents as specified in the protocol, whatever comes later.
- •Male participants with a female partner(s) of childbearing potential must agree to use a highly effective method of contraception, starting with the first dose of IMP through 150 days after last dose of visugromab or nivolumab, or through 180 days after last dose of chemotherapeutic agents as specified in the protocol, whatever comes later. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.
- •Ability to understand the purpose of the trial and voluntary provision of a signed and dated informed consent prior to performing any protocol related procedures (including Screening evaluations) and ability to comply with the trial procedures (including completion of the electronic questionnaires on patient reported outcomes) and any locally required authorization.
- •Demonstrated absence of actionable mutations (e.g. EGFR, ALK, among others) that suggest/require treatment with available targeted agent.
- •Must have failed one line of prior systemic treatment for metastatic NSCLC containing an approved anti PD (L)1 CPI. The minimum treatment duration on this regimen must have been 12 weeks exposure for the CPI with no documented progression in this period. Failure of the prior line of systemic treatment for metastatic NSCLC must have occurred under ongoing CPI treatment. Discontinuation of the prior CPI and line of treatment due to AEs, or any other reason than progression/relapse does not permit enrollment.
- •Participants should not have any contraindication to receive treatment with an anti-PD-(L)1 CPI or docetaxel.
- •Measurable disease determined by the Investigator based upon local radiologist assessment as per RECIST v1.
- •If a target lesion is located in a previously irradiated area, it will be considered measurable if progression (or non reduced size in the past 12 weeks) has been demonstrated in such a lesion post radiotherapy.
- •Age ≥ 18 years on the day of signing the informed consent.
- •Life expectancy of at least 3 months as assessed by the Investigator.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Adequate organ function, defined as: Bone marrow function: Absolute neutrophil count (ANC) ≥ 1,500 /µL, Platelets ≥ 100,000 /µL, Hemoglobin ≥ 10.0 g/dL after ≥ 4 weeks without transfusions. Renal: Calculated creatinine clearance (CrCl) ≥ 50 mL/min. Hepatic: Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels > 1.5 × ULN, Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN (or ≤ 5 × ULN for participants with liver metastases). Endocrine: Thyroid stimulating hormone (TSH) within normal range including participants with thyroid hormone substitution. If TSH is not within normal range at baseline, the participant will still be eligible if total T3 or free T3 and free T4 are within the normal range. Coagulation: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy, Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) ≤ 1.5 × ULN unless the participant is receiving anticoagulant therapy, No evidence for clinically relevant hypo- or hypercoagulability or presence of clinically relevant thrombosis/thrombotic event.
排除标准
- •Presence of predominantly squamous cell histology or predominantly neuroendocrine histology NSCLC (mixed tumors will be categorized by the predominant cell type) or presence of small cell lung cancer elements (ineligibility independent of percentage).
- •Comedication with metformin or metformin-containing antidiabetics in participants with type II diabetes.
- •Chronic systemic corticosteroid treatment for other reasons. Participants with asthma that require intermittent use of bronchodilators, inhaled steroids, or local steroid injections are not excluded from participation.
- •Currently participating in a clinical trial or receiving any investigational therapy or have participated in a trial of an investigational agent in the past 4 weeks or used an investigational device for any disease within 4 weeks prior to administration of any IMP.
- •Presence of active infection requiring systemic therapy.
- •Known history of Human Immunodeficiency Virus (HIV) infection (known HIV 1/2 antibodies [Ab] positive).
- •Known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg result. Active Hepatitis C is defined by a known positive IgM Hepatitis C Virus (HCV) antibody (Ab) result or known quantitative HCV ribonucleic acid (RNA) results greater than the lower limits of detection of the assay.
- •History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant’s participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator.
- •Symptomatic ascites or pleural effusion(s). A participant who is clinically stable following treatment for these conditions (including therapeutic fluid removal) is eligible.
- •Interstitial lung disease or a history of (non-infectious) pneumonitis that required systemic steroids or current pneumonitis.
- •Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the trial.
- •Received a live or live attenuated vaccination within 30 days of planned treatment start.
- •Known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial (including severe alcoholism) or had a recent history (within the last 6 months before planned treatment start) of such abuse, or any other condition that as per Investigator view does not permit trial participation.
- •Participant is under legal guardianship.
- •Prior exposure to visugromab or another anti GDF 15 antibody or to docetaxel.
- •Received more than one line of prior systemic treatment for advanced/metastatic NSCLC.
- •Any acute or chronic major tissue injury that may require maintained GDF-15 function for tissue protection as per Investigator assessment (e.g., diagnosed with myocardial infarction, or liver, kidney, or other major organ failure, all within < 3 months prior to planned treatment start).
- •Major surgery (defined as a surgery which requires general anesthetic and/or involves opening of body cavities), within 4 weeks of the first dose of IMP.
- •Received radiation therapy to the lung that is > 30 Gy within 6 months prior to the first dose of IMP.
- •Received or completed any focal radiotherapy for symptoms within 28 days of the first dose of IMP.
- •Expected to require any other form of antineoplastic therapy during the trial.
- •Known history of allogeneic tissue/solid organ transplant.
- •Clinically active inflammatory bowel disease, active diverticulitis, intra-abdominal abscess, and/or gastrointestinal obstruction.
- •Known history of prior malignancy with the exception that the participant has undergone potentially curative therapy with a minimum of 5 years of complete remission prior to randomization, no evidence of disease recurrence and no further required therapy.
- •Known or detected clinically active central nervous system (CNS) involvement by NSCLC or other tumors, e.g., with symptomatic metastases and/or carcinomatous meningitis. Participants with CNS involvement may be enrolled with mandatory regular imaging of the brain as a site of disease if all CNS lesions fulfill one of the following criteria:- CNS lesions following prior focal radiotherapy or surgery: Clinically stable for at least 14 days post stereotactic radiotherapy, 14 days post whole brain irradiation, and at least 28 days post-surgery as documented by clinical assessment without evidence of new or enlarging brain metastases. Participants must be off steroids for 5 days prior to first dose of trial medication. - Known untreated, but asymptomatic CNS lesions (i.e., no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, no lesion >1.5 cm in diameter). - Clinically stable for at least 4 weeks before planned treatment start.
- •Have one of the following cardiovascular risk factors: Myocardial infarction in the past 3 months before planned treatment start, Uncontrolled heart failure, Uncontrolled ventricular arrhythmia, QT interval corrected for heart rate using Fridericia’s formula interval ≥ 470 ms regardless of sex, A peri/myocarditis in the past 3 months before planned treatment start, A history of ischemic stroke in the past 3 months before planned treatment start.
- •Prior severe hypersensitivity reaction to treatment with another monoclonal antibody (mAb).
- •Known sensitivity to visugromab, nivolumab, and/or docetaxel and any component of these drug products.
- •An active autoimmune disease that has required systemic treatment in past 3 months before planned treatment start (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Local corticosteroid treatment or replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
结局指标
主要结局
Objective response rate (ORR), defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator at any time during the Core Trial Period.
Objective response rate (ORR), defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as assessed by the Investigator at any time during the Core Trial Period.
次要结局
- 1. Incidence, type and severity of adverse events (AEs), recorded as treatment emergent adverse events (TEAEs), treatment related AEs (including immune mediated Adverse Events (imAEs) as AEs of Special Interest (AESIs)) and serious adverse events (SAEs).
- 2. Complete response (CR) rate.
- 3. Partial response (PR) rate.
- 4. Objective response rate (ORR).
- 5. Duration of response (DOR).
- 6. Time to response (TTR).
- 7. Progression free survival (PFS).
- 8. Overall survival (OS).
- 9. Participant weight course over time.
- 10. Maximum concentration (Cmax).
- 11. Minimum concentration (Cmin).
- 12. Participants’ subjective well-being as assessed via the Non-Small Cell Lung Cancer-Symptom Assessment Questionnaire (NSCLC-SAQ).
研究者
Regulatory Affairs
Scientific
CatalYm GmbH
研究点 (32)
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