2024-515393-27-00招募中2 期
A randomized, double-blind, placebo-controlled, Phase 2 study evaluating efficacy and safety of inupadenant in combination with carboplatin and pemetrexed in adults with nonsquamous non-small cell lung cancer who have progressed on immunotherapy
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 131
- 试验地点
- 44
- 主要终点
- Part 1 (Dose-Finding): Incidence of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), AEs leading to dose-modifications or discontinuation, deaths, and clinically significant laboratory abnormalities.
研究概览
简要总结
Part 1 (Dose-Finding): • To evaluate safety and tolerability of inupadenant in combination with carboplatin and pemetrexed • To identify the inupadenant recommended Phase 2 dose (RP2D) to be used in combination with carboplatin and pemetrexed in Part 2 of the study Part 2 (Randomized): • To evaluate efficacy of inupadenant in combination with carboplatin and pemetrexed compared to the efficacy of the placebo in combination with carboplatin and pemetrexed
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Part 2
- 盲法
- Double (Subject, Investigator)
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
- •Have signed an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved informed consent form prior to any study specific evaluation.
- •Be ≥18 years of age at the time informed consent is signed
- •Have histologically or cytologically confirmed diagnosis of metastatic (Stage IV) or locally advanced, unresectable Stage III nonsquamous NSCLC that has relapsed or progressed
- •Have measurable disease as defined by RECIST v1.1 criteria based on local assessment with at least 1 target lesion that has not been previously irradiated
- •PD-L1 expression status must be available prior to study entry. No prespecified PD-L1 expression status is necessary for inclusion (or enrollment)
- •Can provide a tumor sample from an existing biopsy taken within 4 years prior to entering the trial or have at least one lesion that is accessible for a fresh biopsy where safe and feasible
- •Have relapsed or progressed after prior anti PD-1/PD-L1 therapy as follows: - Have received only 1 anti-PD-1/PD-L1 agent in the metastatic setting, without concomitant chemotherapy, and have radiographic progression at least 12 weeks after the start of the anti-PD-1/PD-L1 therapy. One cycle of chemotherapy while awaiting molecular testing results prior to starting the anti-PD-1/PD-L1 agent is allowed. Immuno-oncology (IO)/IO combination therapy (standard or investigational) is allowed. OR - Have received anti-PD-1/PD-L1 therapy concurrently with and/or following chemoradiation in the Stage III unresectable setting and have radiographic progression at least 6 months after the last dose of chemotherapy and at least 12 weeks after the start of the anti-PD-1/PDL1 therapy. Immuno-oncology (IO)/IO combination therapy (standard or investigational) is allowed. Note: Prior re-treatment with the same anti-PD-1/PD-L1 agent as well as prior SABR/SRS are allowed following progression on the anti-PD1/PD-L1 regimen.
- •Have adequate organ function confirmed by the following laboratory values obtained within 14 days prior to treatment assignment: Hematological: - Absolute neutrophil count: ≥1,500 /mL - Platelets: ≥100,000 /mL - Hemoglobin: ≥9.5 g/dL or ≥5.9 mmol/L– 4 weeks without transfusions Renal: - Estimated glomerular filtration rate (Modification of Diet in Renal Disease method) (Levey, 1999) ≥ 60mL/min Hepatic - Total bilirubin OR Direct bilirubin: Total bilirubin ≤1.5× institutional upper limit of normal (ULN). For a participant with Gilbert's syndrome, total bilirubin ≤3.0 × institutional ULN is allowed if the increase is predominantly unconjugated bilirubin.- Alanine transaminase (ALT) and aspartate transaminase (AST): ≤3× ULN; ≤5× ULN if liver metastases Coagulation - International Normalized Ratio (INR) : ≤1.5× ULN unless the participant is receiving anticoagulant therapy.
- •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
排除标准
- •Presence of symptomatic central nervous system (CNS) metastases or leptomeningeal disease. a. Participants with asymptomatic untreated CNS metastases are eligible provided that immediate CNS-specific treatment is unlikely in the Investigator's judgment. b. Participants with previously treated CNS metastases are eligible provided they are neurologically stable and, if receiving corticosteroids for CNS metastases, are on a stable or decreasing corticosteroid dose for at least 2 weeks prior to the start of study treatment c. In participants with known CNS metastases, baseline CNS imaging must be obtained within 4 weeks prior to the start of study treatment.
- •Diagnosis of immunodeficiency or any condition requiring concurrent use of systemic immunosuppressants or corticosteroids (>10mg daily prednisone equivalents).
- •Active infection requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 7 days prior to first dose of study treatment.
- •Oncologic treatment including radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, targeted therapy, and/or experimental drugs administered ≤14 days (<28 days in case of checkpoint inhibitor therapy) prior to first dose of study treatment and/or ongoing adverse effects from such treatment > Grade
- •Major surgical procedure ≤4 weeks prior to first dose of study treatment; participants with major surgical procedure >4 weeks prior to first dose of study treatment must be sufficiently recovered and stable before treatment administration. Please refer to Protocol Section 3.5.2 for other exclusion criteria
- •Presence of active second malignancy, except for: a. History of malignancy that has been successfully treated, with no evidence of active cancer for 1 year prior to enrollment b. Surgically cured and/or low risk tumors e.g., early stage cervical or endometrial cancer, any cancer in situ, non-melanoma skin cancers.
- •Received systemic therapies for NSCLC, in the metastatic or Stage III unresectable setting, other than 6 those described in inclusion criterion
- •Have actionable mutation or genomic alteration in epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), or ROS
- •Additionally, participants with known RET or NTRK rearrangement, BRAF V600E mutation, HER2 mutation, or MET exon 14 skipping mutation are excluded if targeted therapy is available as local standard of care (SOC).
- •Preexisting gastrointestinal disorders/conditions that would, in the opinion of the Investigator, interfere with ingestion or absorption of inupadenant.
- •History of or active (non-infectious) pneumonitis/ interstitial disease or lung fibrosis.
- •Have active or a history of autoimmune disease requiring systemic treatment in the last 6 months or persistent immune-mediated toxicity caused by checkpoint inhibitor therapy > Grade 1, with the exception of residual endocrinopathy being adequately treated, vitiligo, Type 1 diabetes mellitus (T1DM), or psoriasis not requiring systemic therapy. Replacement therapy is allowed.
- •Have known active or chronic hepatitis B or C infection unless treated with antiviral therapy for at least 4 weeks with no detectable viral load at the time of screening; known infection with human immunodeficiency virus (HIV) unless receiving antiretroviral therapy with well-controlled disease documented at the time of screening. Participants are not required to be tested for the presence of such viruses prior to therapy on this protocol in the absence of a history of such infection or unless required by local health authorities.
- •History of life-threatening toxicity related to prior immune therapy or any toxicity resulting in permanent discontinuation from prior immune therapy.
结局指标
主要结局
Part 1 (Dose-Finding): Incidence of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), AEs leading to dose-modifications or discontinuation, deaths, and clinically significant laboratory abnormalities.
Part 1 (Dose-Finding): Incidence of adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), AEs leading to dose-modifications or discontinuation, deaths, and clinically significant laboratory abnormalities.
Part 2 (Randomized): Progression-free survival (PFS), defined as time from randomization to the date of first documented radiological progression using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause
Part 2 (Randomized): Progression-free survival (PFS), defined as time from randomization to the date of first documented radiological progression using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria or death due to any cause
次要结局
- Part 1: ORR; DoR; percent CTS from baseline; DCR, PFS, OS.
- Part 2: Incidence and frequency of AEs, SAEs, and AEs leading to dose modifications or discontinuation, deaths, and clinically significant laboratory abnormalities.
- Part 2: ORR; DoR; percent CTS from baseline; DCR; OS.
- Part 2: Time to definitive deterioration in global health status/quality of life (QoL), shortness of breath and pain per EORTC QLQ-C30 questionnaire. Please refer to Protocol for other secondary endpoints.
研究者
Sally Ross
Scientific
iTeos Belgium
研究点 (44)
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