A Randomized, Open Label, Multicenter, Phase 3 Trial Evaluating the Efficacy and Safety of TAK-928 Versus Docetaxel in Participants With Unresectable Locally Advanced or Metastatic Non-Small Cell Lung Cancer With Disease Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Immunotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 600
- 试验地点
- 46
- 主要终点
- Global Part: Confirmed Objective Response Rate (cORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V)1.1
研究概览
简要总结
Lung cancer is one of the most common forms of cancer. One common type is non-small cell lung cancer (NSCLC). NSCLC happens when abnormal cells in the lungs grow too fast. This can stop the lungs from working normally. This study focuses on NSCLC in later stages (advanced). This means that the cancer has spread to other parts of the body (metastatic) or cannot be removed with surgery (unresectable).
People with unresectable, advanced or metastatic NSCLC often get treatment with immunotherapy and/or platinum-based chemotherapy (such as cisplatin or carboplatin). Immunotherapy helps the body's germ-fighting (immune) system fight cancer. Chemotherapy kills cancer cells or slows their growth. Over time, these treatments may stop working and the cancer can get worse.
Researchers are looking for ways to make immunotherapy work better. One approach is to help the immune system recognize cancer more easily by activating certain cells, called T cells, to attack and kill the tumor cells. TAK-928 is designed to attach to T cells in the tumor and make them more active and abundant. This may help the body fight the cancer and destroy tumor cells.
The main aim of this study is to learn how well TAK-928 works and compares with the usual treatment (also called standard of care), docetaxel, in adults with unresectable, advanced or metastatic NSCLC. Another aim is to learn how safe TAK-928 is in adults with NSCLC.
The participants can be treated for up to 2 years (24 months) depending on how a participant responds, side effects, or other reasons. Researchers will check a participant's condition until the treatment is ended.
During the study, participants will visit the study clinic several times.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Must be able to understand and willing to sign the written informed consent form (ICF), be able to comply with the visit schedule and related procedures specified in the protocol.
- •Male or female participants must be at least 18 years old or the legal age of majority in their country, whichever is greater. For Japan-specific safety run-in (SRI) part of the trial, participants must be Japanese residing in Japan.
- •Have locally unresectable advanced or metastatic histologically or cytologically confirmed squamous NSCLC. Mixed small cell carcinoma, or other pathological components are excluded.
- •Note: For Japan-specific SRI only: Participants' histology is not restricted to squamous NSCLC and may include all metastatic or unresectable solid tumor participants.
- •Have had disease progression on or after prior treatment with anti-PD-1/PD-L1 therapy and platinum-based doublet chemotherapy (for example, carboplatin and paclitaxel), given either concurrently or sequentially. Eligible participants include those that have:
- •- Received platinum-based chemotherapy in combination with anti-PD-1/PD-L1 therapy as the only prior line of therapy.
- •- Received platinum-based chemotherapy and anti-PD-1/PD-L1 therapy sequentially (in either order) as the only 2 prior lines of therapy.
- •Note: For Japan-specific SRI only: Participants must be refractory OR intolerant to standard of care (SOC) treatment.
- •Participants that have received prior anti-PD-1/PD-L1 therapy with curative intent for locally advanced disease are eligible if they meet either of the following criteria:
- •- Received prior platinum-based chemotherapy with or without radiotherapy with maintenance anti-PD-1/PD-L1 therapy for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy.
- •- Received prior peri-operative platinum-based chemotherapy with maintenance anti-PD-1/PD-L1 therapy for resectable Stage II/III and have relapsed within 6 months from the last dose of platinum-based chemotherapy.
- •Note: For Japan-specific SRI only: This criterion is not applicable for Japanese participants enrolled in the SRI part of the trial.
- •Provide formalin-fixed tumor tissue specimen. Fresh biopsies are preferred but archival specimens collected within 2 years before signing the informed consent form are acceptable (blocks or 10-15 unstained slides sectioned 4-5 microns in thickness, if tissue slides, they must be sectioned from blocks less than or equal to (<=) 2 months from date of consent). Formalin-fixed paraffin-embedded (FFPE) blocks are preferred for submission; slides should be sent only if there is a local regulation preventing submission of the FFPE block. Ideally, the archival specimen should be collected subsequent to the most recent systemic therapy.
- •Note: For Japan-specific SRI only: Collection of tumor tissue specimen is not required for Japanese participants enrolled in the SRI part of the trial.
- •Have at least 1 measurable lesion (target lesion) by computed tomography (CT) or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.
- •Lesions that have previously received radiotherapy or intratumoral injection can only be used as measurable lesions if they show progression after treatment (either pathologically confirmed or with observation of radiographic progression more than 3 months after treatment) as per RECIST V1.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 or
- •Expected survival time greater than or equal to (>=) 3 months.
- •Women of childbearing potential (WOCBP) must take a urine or serum pregnancy test, highly sensitive tests are required where available based on region, and must test negative for trial inclusion. WOCBP must agree to use at least 1 form of highly effective contraception and 1 barrier method of contraception during the entire course of treatment and for 6 months after the last dose of trial treatment. Fertile men must agree to use a condom, preferably combined with at least 1 form of acceptable contraception for any WOCBP partner(s) during the entire course of treatment and for 6 months after the last dose of trial intervention.
- •Lactating women must agree to strictly abstain from breastfeeding during the entire Treatment Period and for 6 months after the treatment.
排除标准
- •Women who are pregnant or breastfeeding, or intending to become pregnant before, during, or within 6 months after the last dose of any trial intervention. WOCBP not using and/or not willing to use at least 1 form of highly effective method of contraception and 1 barrier method of contraception or fertile men with WOCBP partner(s) not using and/or not willing to use at least 1 form of acceptable contraception. Note: If in the investigator's judgment, the participant may be pregnant based on the physician's medical interview or other information, the participant will be excluded from the trial irrespective of a negative pregnancy test.
- •Known actionable genomic alteration, including any of the following driver gene mutations:
- •Epidermal growth factor receptor (EGFR): including exon 19 deletion, exon 21 L858R, exon 20 T790M, exon 20 S768I, exon 21 L861Q, exon 18 G719X, and exon 20 insertion mutations.
- •Kirsten rat sarcoma virus (KRAS) G12C mutation.
- •Anaplastic lymphoma kinase (ALK) rearrangement.
- •ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) rearrangement.
- •B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E mutation.
- •Neurotrophic tyrosine receptor kinase (NTRK) 1/2/3 fusion.
- •MET proto-oncogene, receptor tyrosine kinase (MET) exon 14 skipping mutation.
- •RET proto-oncogene (RET) rearrangement.
- •V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2, also known as HER2) mutation.
- •Note: (a) It is not mandatory to have undergone driver gene testing. (b) For Japan-specific SRI only: This criterion is not applicable for Japanese participants enrolled in the SRI part of the trial.
- •Participants with enlarging or symptomatic brain metastases are excluded from the trial. Participants who are neurologically, clinically and radiologically stable >=4 weeks after definitive treatment for brain metastases and participants with small, asymptomatic, incidental, untreated brain metastases that remain radiographically stable >=4 weeks after initial identification may participate in this trial as long as they meet all of the following criteria:
- •No metastases to meninges, midbrain, pons, medulla oblongata (leptomeningeal metastases), or cerebellar metastases.
- •No compression of the aqueduct of Sylvius, no compression of the third or fourth ventricle.
- •No participant with epidural spinal cord compression or spinal cord metastases.
- •Participants must be off steroids for at least 7 days for CNS disease. Systemic steroids of <=10 milligrams per day (mg/day) of prednisone or equivalent are acceptable if needed for other indications.
- •CNS-related symptoms must be stable >=14 days prior to randomization
- •Brain metastases should not be included as RECIST V1.1 target lesions
- •Presence of any of the following hematologic abnormalities at baseline*:
- •Hemoglobin <9 grams per deciliter (g/dL).
- •Absolute neutrophil count (ANC) <1,500 per cubic millimeters (mm^3).
- •Platelet (PLT) count <100 x 10^3/mm^
- •*"Baseline" is defined as the last available observation prior to the first dose of investigational product. Note: Participants must not receive supportive treatments such as blood products (including RBC suspension, apheresis platelets, cryoprecipitation, and so on.) within 7 days of confirming eligibility. Erythropoietin or colony-stimulating factors must not be administered within 28 days of confirming eligibility.
- •Presence of any of the following serum chemistry abnormalities at baseline:
- •Total bilirubin greater than (>) 1.5×upper limit of normal (ULN) except for participants with Gilbert's syndrome with serum bilirubin <=3×ULN or if concurrent conjugated bilirubin <=ULN.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3×ULN; for liver metastasis, AST or ALT >5×ULN.
- •Creatinine clearance (CrCl) <30 milliters per minute (mL/min); the Cockcroft-Gault formula is used to calculate CrCl (using ideal body weight for obese participants and actual body weight for non-obese participants).
- •Albumin <30 grams per liter (g/L).
- •Presence of any of the following coagulation parameter abnormalities at baseline:
- •International normalized ratio (INR) >1.5×ULN (>3×ULN if on stable dose anticoagulation).
- •Partial thromboplastin time (PTT; or activated partial thromboplastin time [aPTT]) >1.5×ULN (>3×ULN if on stable-dose anticoagulation).
- •History of deep venous thrombosis, pulmonary embolism, or any other serious thromboembolic events within 30 days prior to enrollment (implantable port or catheter-related thrombosis, or superficial venous thrombosis are not considered "serious" thromboembolisms). Participants with a history of serious thromboembolic event must be asymptomatic and on stable anticoagulation therapy (if such therapy is deemed necessary by the treating physician).
- •Active uncontrolled bleeding, known bleeding diathesis, or significant concern for risk of acute life-threatening bleeding (for example, radiographic evidence that tumor invades large blood vessels or has unclear boundaries with a major vessel [including aorta, left pulmonary artery, right pulmonary artery, pulmonary vein, superior vena cava, inferior vena cava, and so on], or the investigator judges that the tumor is very likely to invade major vessels with the potential to cause fatal bleeding during the duration of the trial).
- •Presence of clinically significant cardiovascular or cerebrovascular diseases, including:
- •Symptomatic, clinically unstable arrhythmia or arrhythmia requiring clinical intervention.
- •Severe conduction disorders (such as third-degree atrioventricular block and bundle branch block).
- •QT interval corrected for heart rate (QTc interval, calculated using Fridericia's formula) >=480 milliseconds (msec).
- •Uncontrolled hypertension (systolic blood pressure >=160 millimeters of mercury (mmHg) or diastolic blood pressure >=100 mmHg) despite standard treatment.
- •History of myocarditis.
- •Left ventricular ejection fraction <50 percent (%).
- •Congestive heart failure requiring treatment.
- •Class II to IV cardiac insufficiency according to the New York Heart Association functional classification.
- •History of acute coronary syndrome (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to the first dose of investigational product.
- •Cerebrovascular accident or transient ischemic attack within 6 months before the first dose of the investigational product.
- •History of seizures unless controlled on stable dose of antiseizure medications.
- •Cardiac enzymes >=levels consistent with acute myocardial infarction as defined by laboratory-specific criteria. Participants with isolated Grade 1 elevated cardiac enzymes require cardiology clearance and consultation with the sponsor's medical monitor to confirm absence of ongoing myocardial/ischemic disease.
- •History of or current interstitial lung disease (ILD), pulmonary fibrosis, and drug-related, immune-related and radiation pneumonitis; current active pulmonary infection requiring anti-infective therapy; active pulmonary tuberculosis (TB) within 1 year prior to enrollment; severely impaired pulmonary function, including but not limited to the following: pulmonary embolism, severe asthma or chronic obstructive pulmonary disease within 3 months prior to randomization; autoimmune, connective tissue, or inflammatory diseases involving the lungs (such as rheumatoid arthritis, Sjögren's disease, and sarcoidosis); previous unilateral pneumonectomy.
- •Note: Participants with a positive interferon-gamma release assay (IGRA) and negative chest imaging for active pulmonary TB (that is, participants with a history of latent TB) may enroll if they have completed appropriate definitive treatment for latent TB prior to enrollment in the trial (C1D1). Participants with a history of active TB may enroll if they have completed appropriate definitive treatment for active TB more than 1 year before enrollment in the trial (C1D1) and chest imaging at the time of screening is negative for active disease.
- •History of severe, poorly controlled allergies, asthma or atopic dermatitis (except for atopic dermatitis caused by immunotherapy).
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研究组 & 干预措施
Control
Docetaxel or comparable generic brand
干预措施: Control Arm (Drug)
TAK-928
TAK-928 is a first-in-class bispecific monoclonal antibody (mAb) comprised of an interleukin-2 (IL-2) mutein fused with a recombinant anti-programmed cell death protein 1 (anti-PD-1) mAb. TAK-928 was precisely designed and constructed to afford targeted binding of tumor-specific CD8+ T cells (TSTs) that co-express PD-1 and CD25 (IL2Ra) receptors. The mechanism of action of TAK-928 is blocking the PD-(L)1 and activating the IL-2 pathways simultaneously to reverse T cell exhaustion and promote activation of T cells and natural killer (NK) cells, and consequently eliminate tumor cells.
干预措施: TAK-928 (Drug)
结局指标
主要结局
Global Part: Confirmed Objective Response Rate (cORR) as Assessed by Blinded Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version (V)1.1
时间窗: Up to 26 months
cORR is defined as the proportion of participants with confirmed objective response rate (complete response \[CR\] or partial response \[PR\]) per RECIST V1.1 CR is defined as complete disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non- target) must have reduction in short axis to less than (\<) 10 mm. PR is defined as at least a 30 percent decrease in the sum of the diameters of target lesions, taking as reference the Baseline sum diameters.
Global Part: Overall Survival (OS)
时间窗: Up to 26 months
To compare the overall survival (OS) of TAK-928 (treatment group) versus docetaxel (control group) in participants with unresectable locally advanced or metastatic squamous NSCLC with disease progression on or after platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy.
SRI Part: Percentage of Participants with Dose-limiting Toxicities (DLTs)
时间窗: Up to 28 days after first dose (Day 1)
DLT will be defined as any of the adverse events (AEs) specified in the protocol that occur within the DLT observation period, is not attributable to disease or other extraneous factors and potentially related to the intervention following the first dose. Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0.
SRI Part: Percentage of Participants With Adverse Events (AEs), Treatment-Emergent Adverse Events (TEAEs), Immune-Related Adverse Events (irAEs), Serious Adverse Events (SAEs), and TEAEs Leading to Discontinuation and Deaths
时间窗: From screening up to 26 months
AE: Any untoward medical occurrence in a clinical trial participant, temporally associated with the use of trial intervention, whether or not there is a causal relationship with any trial intervention, including, but not limited to, following: Exacerbation of pre-existing medical conditions/diseases (including worsening of symptoms, signs, laboratory abnormalities) temporally associated with the use of trial intervention; any newly developed adverse medical conditions (including symptoms, signs and newly diagnosed diseases) and clinically significant abnormal laboratory values or results. TEAE: Any AE that starts after the first administration of study drug. SAE: Any untoward medical occurrence that meets at least one of the following criteria: Results in death; is life threatening; requires inpatient hospitalization or prolongation of hospitalization. irAEs may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously.
Overall Survival (OS)
时间窗: 37 Months from First Patient In (FPI) (event driven)
To compare the overall survival (OS) of IBI363 (treatment group) vs. docetaxel (control group) in participants with unresectable locally advanced or metastatic squamous NSCLC with disease progression on or after platinum-based chemotherapy and anti-PD-1/PD-L1 immunotherapy.
次要结局
- Pharmacokinetic parameters including Clearance (CL) of IBI363(44 months)
- Progression-free survival (PFS)(44 months)
- Objective Response Rate (ORR)(44 months)
- Disease Control Rate (DCR)(44 months)
- Duration of Response (DOR)(44 momths)
- Time to Response (TTR)(44 months)
- Safety Profile(44 months)
- Pharmacokinetic parameters including Terminal Half-Life (t½) of IBI363(44 months)
- Pharmacokinetic parameters including Volume of Distribution (Vd) of IBI363(44 months)
- Number of Participants Who Develop Anti-Drug Antibodies (ADA) to IBI363 (immunogenicity)(44 months)
- Change from Baseline in Global Health Status / Quality of Life (QoL) Score Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(44 months)
- Global and SRI Part: Objective Response Rate (ORR) as Assessed by Investigator per RECIST V1.1(Up to 26 months)
- Global Part: Progression-free survival (PFS), as Assessed by BICR and Investigator per RECIST V1.1(Up to 26 months)
- Global Part: Disease Control Rate (DCR) as Assessed by BICR and Investigator per RECIST V1.1(Up to 26 months)
- Global Part: Duration of Response (DOR) as Assessed by BICR and Investigator per RECIST V1.1(Up to 26 months)
- Global Part: Time to Response (TTR) as Assessed by BICR and Investigator per RECIST V1.1(Up to 26 months)
- SRI Part: DCR as Assessed by Investigator per RECIST V1.1(Up to 26 months)
- SRI Part: DOR as Assessed by Investigator per RECIST V1.1(Up to 26 months)
- SRI Part: TTR as Assessed by Investigator per RECIST V1.1(Up to 26 months)
- Global Part: Percentage of Participants With TEAEs, irAEs, SAEs, AESIs and TEAEs Leading to Discontinuation and Deaths(From screening up to 26 months)
- Global and SRI Part: Pharmacokinetic parameters including Terminal Half-Life (t½) of TAK-928(Day 1 pre-dose and at multiple time points post-dose (up to 25 months))
- Global and SRI Part: Pharmacokinetic parameters including Clearance (CL) of TAK-928(Day 1 pre-dose and at multiple time points post-dose (up to 25 months))
- Global and SRI Part: Pharmacokinetic parameters including Volume of Distribution (Vd) of TAK-928(Day 1 pre-dose and at multiple time points post-dose (up to 25 months))
- Global and SRI Part: Number of Participants Who Develop Anti-Drug Antibodies (ADA) and/or Neutralizing Antibody (Nab) to TAK-928(Up to 25 months)
- Global Part: Time to Deterioration (TTD) in in GHS/QoL and Dyspnea as Measured by the EORTC QLQ-C30(Up to 25 months)
- Global Part: Change from Baseline in Global Health Status (GHS)/ Quality of Life (QoL) Score (Item 29 & 30) and Dyspnea (Item 8) Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(Up to 25 months)
- Global Part: Change From Baseline in Functioning Scale Scores as Measured by the EORTC QLQ-C30(Up to 25 months)
- Global Part: Change From Baseline in Symptom Scale Scores as Measured by the EORTC QLQ-C30(Up to 25 months)
- Global Part: Change From Baseline in Single Item Symptom Questions as Measured by the EORTC QLQ-C30(Up to 25 months)
- Global Part: Change From Baseline in Health Utility Scores as Measured by EuroQol Five-dimensional Five-level Questionnaire (EQ-5D-5L)(Up to 25 months)
- Global Part: Change From Baseline in Symptoms of Lung Cancer as Assessed With the EORTC QLQ- Lung Cancer (LC) 13 (QLQ-LC13)(Up to 25 months)
- Disease Control Rate (DCR)(44 months)
- Progression-free survival (PFS)(44 months)
- Objective Response Rate (ORR)(44 months)
- Duration of Response (DOR)(44 momths)
- Time to Response (TTR)(44 months)
- Pharmacokinetic parameters including Terminal Half-Life (t½) of IBI363(44 months)
- Change from Baseline in Global Health Status / Quality of Life (QoL) Score Using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(44 months)
- Safety Profile(44 months)
- Pharmacokinetic parameters including Clearance (CL) of IBI363(44 months)
- Pharmacokinetic parameters including Volume of Distribution (Vd) of IBI363(44 months)
- Number of Participants Who Develop Anti-Drug Antibodies (ADA) to IBI363 (immunogenicity)(44 months)