A Multi-arm, Phase 1b, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9291 in Combination With Ascending Doses of Novel Therapeutics in Patients With EGFRm+ Advanced NSCLC Who Have Progressed Following Therapy With an EGFR TKI.

AstraZeneca0 个研究点目标入组 67 人开始时间: 2014年9月26日最近更新: 2023年10月17日

试验速览

阶段: 1 期
状态: 已完成
发起方: AstraZeneca
入组人数: 67

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional

入排标准

年龄范围: >= 18age old 至 ot applicable（—）
性别: All

入选标准

•Inclusion Criteria Signed informed consent Male or female aged at least 18 years and older. Patients from Japan aged at least 20 years.
•Histological or cytological confirmation of EGFRm + NSCLC. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including exon 19 deletion and L858R). Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI eg, gefitinib or erlotinib. These patients must have radiological progression (as per site assessment) on the last treatment administered prior to enrolling in the study.
•At least one lesion, not previously irradiated, not biopsied during the screening period, that can be accurately measured at baseline as 10 mm or more in the longest diameter (except lymph nodes which must have short axis 15 mm or more) with computerised tomography (CT) or magnetic resonance imaging (MRI) which is suitable for accurate repeated measurements. Adequate haematological, liver and renal function as well as coagulation parameters.
•ECOG/WHO performance status of 0 or 1 or KPS >80. Ability to swallow and retain oral medications. Prior to study entry, local confirmation of tumour cMET status is acceptable, a central result will be confirmed retrospectively. Local confirmation of tumour T790M status is acceptable if performed with an approved test and agreed by AstraZeneca.
•Agree to use adequate contraceptive measures.
•Part C monotherapy cohort
•- Histological or cytological documented, locally advanced solid malignancies, excluding lymphoma, that is refractory to standard therapies or for which no standard therapies exist.
•- Radiological documentation of disease progression on the last treatment administered prior to enrolling in the study.
•- Evaluable or measurable disease.
•Part C combination therapy cohort
•- Histological or cytological confirmation of EGFRm + NSCLC. Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including exon 19 deletion and L858R).
•- Radiological documentation of disease progression while on a previous continuous treatment with an EGFR TKI eg, gefitinib or erlotinib. These patients must have radiological progression (as per site assessment) on the last treatment administered prior to enrolling in the study

排除标准

•Exclusion Criteria Treatment with an EGFR TKI within approximately 5x half-life (eg, within 8 days for erlotinib, gefitinib or afatanib, or within 10 days for dacomitinib) of the first dose of study treatment. Any cytotoxic chemotherapy, investigational agents or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment. Patients currently receiving medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior). For AZD6094 patients currently receiving prior to receiving the first dose, medications known to be strong inhibitors of CYP1A2.
•Prior AZD9291 dosing in the present study. Prior treatment with a 3rd generation (T790M-directed) therapy (eg, AZD9291, rociletinib or HM61713) outside of this study is permitted if allocated to the 3rd generation EGFR TKI cohort. Prior or current treatment with AZD6094 or another cMET inhibitor (eg, foretinib, crizotinib, cabozantinib, onartuzumab) if allocated to AZD9291 plus AZD6094 combination. Radiotherapy with a limited field of radiation for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow or with a wide field of radiation which must be completed within 4 weeks or more of the first dose of study treatment. Major surgical procedure, or significant traumatic injury within 4 weeks of the first dose of study treatment, or have an anticipated need for major surgery during the study.
•Currently receiving treatment with warfarin sodium. LMWH is allowed. Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy. Any of the following cardiac diseases currently or within the last 6 months: Unstable angina pectoris, Congestive heart failure (NYHA Grade 2 or more), Acute myocardial infarction, Stroke or transient ischemic attack.
•Known hypersensitivity to the active or inactive excipients of AZD6094. Uncontrolled hypertension (BP 150/95mmHg or more despite medical therapy) Mean resting correct QT interval (QTcF) >470 msec for women and >450 msec for men or factors that may increase the risk of QTcF prolongation such as chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval and cause Torsade de Pointes.
•Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms (ECGs), e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec. Serious underlying medical condition at the time of treatment that would impair the ability of the patient to receive protocol treatment.
•Active hepatitis B (positive HBsAg result) or hepatitis C (HCV). Patients with a past or resolved HBV infection are eligible if negative for HBsAg and positive for anti-HBc or positive for HBsAg, but for > 6 months have had normal transaminases and HBV DNA levels between 0-2000 IU/ml (inactive carrier state) and willing to start and maintain antiviral treatment for at least the duration of the study. HBV DNA levels > 2000 IU/ml but on prophylactic antiviral treatment for the past 3 months and will maintain the anti

研究者

发起方

AstraZeneca

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