An open-label, multicenter, Phase 1/2 study of radium-223 dichloride in combination with pembrolizumab in participants with stage IV non-small cell lung cancer

Bayer Consumer Care AG0 个研究点目标入组 154 人开始时间: 2020年3月24日最近更新: 2020年6月15日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: Bayer Consumer Care AG
入组人数: 154

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 clinical trial of medicinal product

入排标准

性别: All

入选标准

•1. Participant must be =18 yrs (or age of legal maturity) at time of signing ICF
•2. Histologically / cytologically confirmed diagnosis of stage IV NSCLC. Phase 1 incl. participants meeting either Cohort 1 / Cohort 2 inclusion criteria as outlined below
•a. Phase 2 Cohort 1:
•- No EGFR sensitization (activating) mutation or ALK/ROS1 rearrangement
•- Treatment naïve (no prior systemic therapy) for their metastatic NSCLC. Completion of treatment with chemotherapy as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 mths prior to diagnosis of metastatic disease
•- PD-L1 TPS =50% as per local assessment
•b. Phase 2 Cohort 2:
•- Progression on prior treatment with immune checkpoint inhibitor
•- If no EGFR sensitization (activating) mutation or ALK/ROS1 rearrangement
•1. 1 or 2 prior lines of therapies for metastatic NSCLC
•- If EGFR sensitization (activating) mutation or ALK/ROS 1 rearrangement
•1. Prior treatment with appropriate tyrosine kinase inhibitor
•2. At least one & not more than 3 prior lines of therapy for metastatic NSCLC
•- Availability of tumor specimen for determination of PD-L1 status
•3. Measurable disease per RECIST v1.1 as assessed by local site investigator/radiologist. Lesions situated in previously irradiated area considered measurable if progression has been demonstrated in such lesions.
•4. At least 2 skeletal metastases identified at baseline confirmed by MRI / CT
•5. ECOG Performance Status of 0/1
•6. Adequate bone marrow & organ function as assessed by following lab. tests
•a. Hemoglobin =9g/dL without transfusion / erythropoietin within last 4 wks
•b. ANC =1500/mm3
•c. Platelet count =100000/mm3 without platelet transfusion within last 4 wks
•d. ALT & AST =2.5 x upper limit of normal (=5 X ULN in case of liver metastases)
•e. Total bilirubin =1.5XULN
•f. Creatinine =1.5XULN or estimated creatinine clearance =30 mL/min as calculated using Cockcroft-Gault equation
•g. Prothrombin International normalized ratio or PT & aPTT =1.5×ULN unless participant receiving anticoagulant therapy (as long as PT/ aPTT within therapeutic range of intended use of anticoagulants)
•- Participants being treated with anticoagulant will be allowed to participate provided no prior evidence of underlying abnormality in these parameters exists. Anticoagulants that require monitoring, standards should be considered & controlled by investigator. New oral anticoagulants, individual risk benefit in accordance with the applicable labels &/or local guidelines should be carefully assessed
•7. Female participants of child-bearing potential must have negative serum pregnancy test within 7 days before start of study drug administration. Post-menopausal females & surgically sterilized females are exempt from pregnancy test
•8. Females of childbearing potential & males must agree to use highly effective methods of birth control (i.e failure rate <1% per yr) from signing ICF until at least 120 days after last administration of pembrolizumab or 6 mths after last administration of radium-223 dichloride, whatever comes later, when sexually active (plus an additional 30 days [a menstruation cycle] for female participants plus an additional 75 days [a spermatogenesis cycle] for male participants who must refrain from donating sperm during this period).
•Highly effective methods of contraception for female participants include: (i) combined hormonal contraception associated with inhibition of ovulation; (ii) progestogen-only hormonal contrac

排除标准

•1. Previous / concurrent cancer within 3 years prior to enrollment except for curatively treated carcinoma in situ (e.g., breast carcinoma, cervical cancer, prostate carcinoma, non-melanoma skin cancer, and superficial bladder tumors).
•2. Condition by Cohort & Phase:
•a. Phase 2 Cohort 1 (& participants eligible for 1st line treatment in Phase 1): Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, cluster of differentiation [CD]137).
•b. Phase 2 Cohort 2 (& participants eligible for = 2nd line treatment in Phase 1): Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137) and was discontinued from that treatment due to a Grade 3 or higher irAE.
•3. Known active CNS metastases &/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (i.e., without evidence of progression for at least 4 wks by repeat imaging) (note that the repeat imaging should be performed during study screening), clinically stable, & without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
•4. Active autoimmune disease that has required systemic treatment in the past 2 yrs (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy is not considered a form of systemic treatment & is allowed.
•5. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
•6. Major surgical procedure / significant traumatic injury within last 28 days. Note: If participants received major surgery, they must have recovered adequately from the toxicity &/or complications from the intervention prior to starting therapy. Central line surgery is not considered major surgery.
•7. Non-healing wound, non-healing ulcer / non-healing bone fracture.
•8. Evidence / history of any bleeding diathesis, irrespective of severity.
•9. Known history / presence of osteonecrosis of jaw.
•10. Known hypersensitivity to the active substance or to any of the excipients of radium-223 dichloride or pembrolizumab
•11. Seizure disorder requiring medication.
•12. Ongoing infection >Grade 2 NCI-CTCAE v.5.0 requiring systemic therapy
•13. Significant acute GI disorders with diarrhea as major symptom e.g., Crohn’s disease, malabsorption, or = NCI-CTCAE v.5.0 Grade 2 diarrhea of any etiology.
•14. Pregnant / breast-feeding participants.
•15. CHF = NYHA class 2.
•16. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 mths).
•17. Myocardial infarction in the last 6 months
•18. Uncontrolled cardiac arrhythmias (= grade 3 CTC v5.0).
•19. History of osteoporotic fracture
•20. Known history of Hepatitis B (defined as HBsAg reactive or detectable HBV DNA or known active Hepatitis C virus (defined as HCV RNA is detected) infection. Note: No testing for Hepatitis B & Hepatitis C is required unless mandated by local authority.
•21. Known HIV. No HIV testing required unless mandated by local authority.
•22. Previous (within the last 4 wks of the planned first dose of study treatment) or concomitant participation in another clinical study with investigational medicinal product(s). Note: Participants must have recovered from all AEs due to previous therapies

研究者

发起方

Bayer Consumer Care AG

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