2024-511007-41-00已完成2 期
Phase 1b/2a safety and tolerability study of bemcentinib with pembrolizumab/carboplatin/pemetrexed in subjects with untreated advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) without/with a STK11 mutation.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 27
- 主要终点
- Phase 1b: The incidence of dose limiting toxicities (DLTs) during a 21-day assessment period in treatment cycle 1 (i.e., the first 21 days from cycle 1 day 1 (C1D1) for each subject) Phase 2a: Objective response rate (ORR - complete response and partial response per RECIST 1.1) at 6 and 12 months.
研究概览
简要总结
Phase 1b: To determine the safety and tolerability of the combination of bemcentinib with chemo-immunotherapy (CIT) to identify the recommended phase 2 dose (RP2D) when administered as first line (1L) treatment in subjects with advanced (Stage IIIb/IIIC) or metastatic (Stage IV) non-squamous NSCLC with no actionable mutations.
Phase 2a: To determine the anti-tumor activity of the combination of bemcentinib with CIT when administered as 1L treatment in subjects with advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC with STK11 mutation and no actionable mutations.
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
- •The subject (or legally acceptable representative, if applicable) must provide written informed consent for the study prior to any screening procedures.
- •Be ≥ 18 years of age on the day of signing the informed consent.
- •Have a histologically- or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIc) or metastatic (Stage IV) (AJCC Edition 8) non-squamous NSCLC not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 1b).
- •Have a histologically- or cytologically confirmed diagnosis of advanced (Stage IIIb/IIIC) or metastatic (Stage IV) (AJCC, Edition 8) non-squamous NSCLC with STK11m mutation, not amenable to curative therapy, irrespective of PD-L1 status and without actionable mutations (Phase 2a).
- •Participants who received prior neo-adjuvant or adjuvant/consolidation treatment (radiotherapy, chemotherapy, immunotherapy) or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 6 months since the last dose of chemotherapy, immunotherapy and/or radiotherapy before enrollment.
- •Have measurable disease per RECIST 1.1 as assessed by the investigator. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
排除标准
- •Has received any prior chemotherapy or biological therapy for advanced (Stage IIIb/IIIc) or metastatic (Stage IV) non-squamous NSCLC.
- •Has any actionable mutation that is considered targetable with first-line treatment.
- •Has a known history of prior malignancy except if the subject has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy.
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate, provided they are radiologically stable, i.e. without evidence of progression for at least 2 weeks and have no evidence of new or enlarging brain metastases and are off steroids 7 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Subjects with asymptomatic brain metastases (i.e. no neurological symptoms, no requirements for corticosteroids, and no lesion >1.5cm) may participate but will require regular imaging of the brain as a site of disease. Subjects who have experienced an acute neurological event (e.g. intracranial or subarachnoid haemorrhage, stroke, intracranial trauma) within 6 months prior to study enrolment will be excluded.
- •History of the following cardiac conditions: a. Congestive cardiac failure of >Grade II severity according to the New York Heart Association (NYHA) or resistant or inadequately treated heart failure. b. Ischemic cardiac event including myocardial infarction or hospitalization for unstable angina within 3 months prior to first dose. c. Abnormal left ventricular ejection fraction on echocardiography or multigated acquisition scan (MUGA) (less than the lower limit of normal for a subject of that age at the treating institution or <45%, whichever is lower), or history of cardiomyopathy or left ventricular hypertrophy. d. Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e. sustained systolic blood pressure (BP) >160 mmHg or diastolic BP >90 mmHg), or need to change medication due to lack of disease control within 12 weeks prior to the provision of consent. e. History or presence of sustained bradycardia (≤55 bpm) or history of symptomatic bradycardia, left bundle branch block, cardiac pacemaker or significant arrhythmias or any conduction disorder within 6 months prior to dosing as defined by the need for treatment. f. Family history of long QTc syndrome or ventricular arrhythmias; personal history of long QTc syndrome or previous drug induced QTc prolongation of at least Grade 3 (QTc >500ms). g. Presence of any other risk factors that increase the risk of QTc prolongation, specifically, hypokalemia or hypomagnesemia (if corrected the subject may be enrolled) or inadequately treated hypothyroidism (defined as thyroid stimulating hormone (TSH) below the expected range). h. Current treatment with any agent known to cause QT prolongation and have a risk for Torsades de pointes (TdP), which cannot be discontinued at least 5 and ½ half-lives or 2 weeks prior to the first dose of study treatment, with the exception of antiemetics (e.g. ondansetron) which may be required. Please see https://crediblemeds.org for a list of medications with known Torsade de Point risk that need to be excluded.
结局指标
主要结局
Phase 1b: The incidence of dose limiting toxicities (DLTs) during a 21-day assessment period in treatment cycle 1 (i.e., the first 21 days from cycle 1 day 1 (C1D1) for each subject) Phase 2a: Objective response rate (ORR - complete response and partial response per RECIST 1.1) at 6 and 12 months.
Phase 1b: The incidence of dose limiting toxicities (DLTs) during a 21-day assessment period in treatment cycle 1 (i.e., the first 21 days from cycle 1 day 1 (C1D1) for each subject) Phase 2a: Objective response rate (ORR - complete response and partial response per RECIST 1.1) at 6 and 12 months.
次要结局
- Phase 1b: - ORR (complete response and partial response per RECIST 1.1) Phase 2a: - The frequency and percentage of AEs; assessment of safety laboratory parameters, vital signs, and ECGs per CTCAE
- Phase 1b: - Disease control rate (DCR) (complete response, partial response, and stable disease per RECIST 1.1) Phase 2a: - DCR (complete response, partial response, and stable disease)
- Phase 1b: - Duration of response (DOR) Time of first response to progressive disease as assessed per RECIST 1.1) Phase 2a: - DOR
- Phase 1b: - Overall survival Phase 2a: - Progression free survival (PFS)
- Phase 2a: - Time to progression (TTP)
- Phase 2a: - Overall survival
- Phase 2a: - PK exposure (Cmax, AUC, and t½)
研究者
Clinical Project Manager
Scientific
Bergenbio ASA
研究点 (27)
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