Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Conditions
Interventions
investigational material(s)
Generic name etc : Poziotinib
INN of investigational material : -
Therapeutic category code : 429 Other antitumor agents
Dosage and Administration for Investigational mater
Sponsors
Spectrum Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patient is at least 20 years of age 2. Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements 3. Phase 2: If an archival tissue sample is not available, a tumor biopsy will be required. 4. Previously treated patient with histologically or cytologically confirmed (archival tissue accepted) locally advanced or metastatic non-small cell lung cancer (NSCLC) and is not a candidate for definitive therapy -Phase 1: No test for mutational status is required -Phase 2: Documented EGFR or HER2 exon 20 insertion mutation (including duplication mutations) in NSCLC patients. Patients will be enrolled based on documentation of mutational status using PCR or a validated next generation sequencing detection analysis test. -Documented EGFR exon 20 insertion mutation, including D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other EGFR exon 20 in-frame insertion mutation (including duplications). -Documented HER2 exon 20 insertion mutation, including A775_G776insYVMA, G776_V777insVC, or P780_Y781insGSP, or any other HER2 exon 20 in-frame insertion mutation (including duplications). 5. Patient has measurable NSCLC disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Metastatic lesions in bone, CNS, or in brain cannot be used for target lesions. 6. Prior treatment status: -Phase 1: Patient with refractory NSCLC to available standard therapies -Phase 2: Progression after at least one systemic therapy for locally advanced or metastatic disease 7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 8. Patient has recovered from prior systemic therapy for metastatic disease to Grade ?1 for non-hematologic toxicities (except for Grade ?2 peripheral neuropathy) and has adequate hematologic, hepatic, and renal function at Baseline, as defined by: -Leukocytes >=3.0*109/L -Absolute neutrophil count (ANC) must be >=1.5*109/L -Platelet count >=100*109/L -Hemoglobin >=9.0 g/dL -Total bilirubin <=2 mg/dL; if hepatic metastases are present, <=2.5*ULN -SGOT (AST) and SGPT (ALT) <=2.5*ULN with the following exception; Patients with liver metastases AST, ALT <=5*ULN 9. Patient is willing to practice 2 forms of contraception, one of which must be a barrier method. Female patients of childbearing potential must use an effective method of birth control (e.g., oral contraceptive, intrauterine device, bilateral tubal ligation/occlusion, condoms, or diaphragm, not engaging in sexual intercourse) during treatment period and 3 months thereafter. Males must use an effective method of birth control (e.g., condoms, vasectomy, not engaging in sexual intercourse) during treatment period and 3 months thereafter. 10. Females of childbearing potential must have a negative pregnancy test within 7 days prior to Day 1. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) with no other medical reasons or who are surgically sterilized do not require this test.
Exclusion criteria
Exclusion criteria: 1. Phase 2 : Patient has EGFR T790M mutation or any other acquired EGFR exon 20 point mutation 2. Phase 2 : Patient has had previous treatment with poziotinib. The currently approved TKIs that are not considered to be exon 20 insertion-selective are permissible. 3. Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks prior to Cycle 1, Day 1;local radiation therapy for bone pain may be allowed. 4. Patient has used strong inhibitors/inducers of CYP3A4 and CYP2D6 within 1 month prior to Cycle 1, Day 1. 5. Patient has brain metastases and is clinically symptomatic, requires high dose or increasing doses of systemic corticosteroids, or needs any anticonvulsant therapy for metastatic brain disease. 6. Patient has a high risk for or history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment. Cardiac ejection fraction =2 skin disorder, rash, mucositis, or skin infection that needs medication or therapy or existing Grade >=2 skin toxicity from previous therapies; Grade >2 neuropathy, Grade >=2 pneumonitis. 10. Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (eg, Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy 11. Patient has an active liver disease or biliary tract disease (except for Gilbert's disease, asymptomatic biliary stones, liver metastasis, or stabilized chronic liver diseases). Patient has active HBV or HCV infection. 12. Patient is HIV antibody positive. 13. Patient currently has or has had interstitial lung disease in the past 14. Patient has known hypersensitivity to poziotinib or has a history of allergic reactions attributed to chemically similar compounds or other tyrosine kinase inhibitors (TKIs) 15. Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would not be appropriate for this study 16. Patient has unstable, uncontrolled, active bleeding disorders that the investigator considers that the patient could be at increased risk or not be suitable for treatment in this study 17. Patient is pregnant. 18. Women who are breastfeeding or women who are not willing to stop breastfeeding during study treatment period and for 30 days after the last dose of study drug.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| efficacy Phase 1: Dose-Finding - Maximum Tolerated Dose or Maximum Administered Dose Phase 2: Efficacy - Objective Response Rate | — |
Secondary
| Measure | Time frame |
|---|---|
| efficacy pharmacokinetics safety Phase 1: Dose-Finding - Pharmacokinetics of poziotinib and M1 and M2 metabolites - Safety and Tolerability Phase 2: Efficacy - Disease Control Rate - Duration of Response - Progression-Free Survival - Pharmacokinetics of poziotinib and M1 and M2 metabolites - Safety and Tolerability | — |
Countries
Japan
Contacts
Public ContactjRCT Inquiry Contact IQVIA Services Japan K.K.
IQVIA Services Japan K.K.
Outcome results
None listed