Treatment for advanced or metastatic NSCLC in combination with erlotinib in subjects who are epidermal growth factor receptor (EGFR) treatment naïve after failure of at least one prior chemotherapy regimen MedDRA version: 14.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: PT Classification code 10029521 Term: Non-small cell lung cance
Conditions
Interventions
Product Name: U3-1287 (AMG 888)
Product Code: U3-1287 (AMG 888)
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 1262787-83-6
Current Sponsor code: U3-1287
Concentration unit: mg
Sponsors
DAIICHI SANKYO DEVELOPMENT LTD.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women = 18 years old. 2. Histologically or cytologically confirmed NSCLC with either: - Metastatic disease (Stage IV) OR - Stage IIIB disease not amenable to surgery or curative intent. 3. Disease progression or recurrence following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months) documented by radiographic assessment. 4. Measurable disease per RECIST guidelines Version 1.1. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 6. Hematological function, as follows: - Absolute neutrophil count (ANC) = 1.5 × 10e9/L - Platelet count = 100 × 10e9/L - Hemoglobin = 9 g/dL. 7. Renal function, as follows: - Calculated creatinine clearance = 60 mL/min using the modified Cockroft-Gault equation or serum creatinine = 1.5 x ULN. 8. Hepatic function, as follows: - Aspartate aminotransferase (AST) = 2.5 ×upper limit of normal (ULN) (if liver metastases are present, =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Left ventricular ejection fraction (LVEF) 100 mmHg or systolic > 140 mmHg). It is permissible for the subject to receive treatment with antihypertensive medication to maintain blood pressure within required parameters. 9. Clinically significant electrocardiogram (ECG) changes that obscure the ability to assess the RR, PR, QT, QTc, and QRS intervals. 10. Ascites or pleural effusion requiring chronic medical intervention. 11. Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure (New York Heart Association >Class II), unstable angina, or unstable cardiac arrhythmia requiring medication. 12. Treatment with anticancer therapy, antibody-based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study drug treatment or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment or treatment with small molecule tyrosine kinase inhibitors (TKIs) within 2 weeks before study drug treatment. Prior and concurrent use of hormone replacement therapy is permitted. 13. Therapeutic radiation therapy or major surgery within 4 weeks before study drug treatment or palliative radiation therapy within 2 weeks before study drug reatment. Radiation treatment to all sites of measureable disease unless progression is documented after radiation. No target lesion should be selected within the reviously irradiated field unless there was progression at that lesion following radiation. 14. Participated in clinical drug trials within 4 weeks (2 weeks for small molecule TKIs) before study drug treatment. Current participation in other investigational procedures. 15. Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. 16. History of hypersensitivity to any of the study drugs or to any excipients. 17. Concurrent use of CYP3A4 inducers or inhibitors. 18. Any known pre-existing condition including substance abuse that could interfere with subject’s participation in and completion of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase 1b Portion - To evaluate the safety and tolerability of the combination of U3-1287 (AMG 888) and erlotinib in subjects with advanced or metastatic NSCLC. - To determine the recommended dose of U3-1287 (AMG 888) for Phase 2 study (RP2D)in combination with erlotinib. Phase II Portion - To evaluate progression-free survival (PFS) among all randomized subjects treated with erlotinib in combination with high and low doses of U3-1287 (AMG 888) compared to erlotinib plus placebo. - To evaluate the safety profile of the combination of U3-1287 (AMG 888) and erlotinib. ;Secondary Objective: Phase Ib Portion - To assess tumor response of U3-1287 (AMG 888) when combined with erlotinib. - To assess the pharmacokinetic (PK) parameters of U3-1287 (AMG 888) when combined with erlotinib. Phase II Portion - To evaluate overall survival, objective response rate (ORR), duration of response, time to response, time to disease progression, duration of stable disease, and disease control rate (complete response [CR] + partial response [PR] + stable disease [SD]) among all randomized subjects treated with erlotinib in combination with high and low doses of U3-1287 (AMG 888) compared to erlotinib plus placebo. - To assess the PK parameters of U3-1287 (AMG 888) when combined with erlotinib. - To assess the PK parameters of erlotinib when combined with U3-1287 (AMG 888). - To evaluate the incidence of HAHA formation (anti-U3-1287 [AMG 888] antibodies). ;Primary end point(s): • Treatment-emergent AEs • Clinically significant or = grade 3 events according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 in safety laboratory tests, physical examinations, ECGs, echocardiograms, or vital signs • Incidence of DLTs (used to identify RP2D, if applicable) - Phase 1b • PFS - Phase 2 ;Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): For both Phase 1b and Phase 2 · PK parameters (Cmin, Cmax and AUC) of U3-1287 (AMG 888) when combined with erlotinib · PK parameters (Cmin, Cmax and AUC) of erlotinib when combined with U3-1287(AMG 888) · HAHA profile for U3-1287 (AMG 888) · Best overall tumor response For Phase 2 only · Overall survival (OS) · ORR · Duration of response · Time to response · Duration of stable disease (SD) · Time to disease progression (TTP) · Disease control rate (CR+PR+SD) ;Timepoint(s) of evaluation of this end point: 12 months | — |
Countries
Austria, Belgium, Bulgaria, Germany, Hungary, Israel, Italy, Lithuania, Romania, Slovenia, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information
Daiichi Sankyo Development Limited
Outcome results
None listed