A study evaluating the safety and efficacy of radium-223 dichloride in combination with pembrolizumab in lung cancer patients
- Conditions
- Stage IV non-small cell lung cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003704-39-GB
- Lead Sponsor
- Bayer Consumer Care AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 154
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method