Clinical Trials

Inclusion Criteria:

• Patient is at least 18 years of age.
• Patient must be willing and capable of giving written Informed Consent, adhering to dosing and visit schedules, and meeting all study requirements.
• Patient has histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) that is not amenable to treatment with curative intent.
• Prior treatment status:
  • Cohorts 1 and 2: Patient has had at least one prior systemic treatment for locally advanced or metastatic NSCLC;
  • Cohorts 3 and 4: Patient is treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with poziotinib as determined by the Investigator. Adjuvant/neo-adjuvant therapies (chemotherapy, radiotherapy, or investigational agents) are permissible as long as they end at least 15 days prior to study entry;
  • Cohort 5: Patients who meet the criteria for enrollment in Cohort 1 to 4, but the enrollment in the respective cohort has been closed;
  • Cohort 6: Patients with EGFR mutation-positive NSCLC who progressed while on treatment with first-line osimertinib;
  • Cohort 7: Patient has had at least one prior systemic treatment for locally advanced or metastatic NSCLC.
• Tissue and plasma samples for mutation confirmation:
  • Cohorts 1 to 5: Patient has adequate tumor tissue obtained from a biopsy or surgical procedure to enable molecular profiling for retrospective central laboratory confirmation of the mutation. If tissue is not available, the patient must have biopsy accessible disease and must be willing to undergo a biopsy to provide an appropriate tissue sample prior to receiving treatment in the study;
  • Cohort 6: A tissue sample must be provided after osimertinib progression;
  • Cohort 7: Either tissue or plasma samples are acceptable for enrollment.
• Patient is positive for EGFR or HER2 mutations based on:
  • Cohorts 1 and 3: Documented EGFR exon 20 insertion mutation (including duplication mutations) using a next generation sequencing diagnostic test, such as OncoMine Comprehensive Assay (OCA) or FoundationOne Assay, or by an FDA approved test (eg, cobas® EGFR mutation test v2 or therascreen EGFR RGQ PCR kit) performed by a US CLIA certified and locally licensed clinical laboratory or similarly accredited lab for ex-US sites using tissue samples;
  • Cohorts 2 and 4: Documented HER2 exon 20 insertion mutation (including duplication mutations) using a next generation sequencing diagnostic test, such as OncoMine Comprehensive Assay (OCA) or FoundationOne Assay, performed by a US CLIA certified and locally licensed clinical laboratory or similarly accredited lab for ex-US sites using tissue samples;
  • Cohort 5: Documented EGFR or HER2 exon 20 insertion mutations using tissue samples using the criteria described for Cohorts 1 to 4;
  • Cohort 6: Documented acquired EGFR mutation who have progressed while on first-line osimertinib treatment using tissue tested with a next-generation sequencing assay;
  • Cohort 7: Documented EGFR or HER2 activating mutations (see table below) using tissue tested with a next-generation sequencing assay or plasma tested with a Guardant assay.
• Patient has measurable NSCLC disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Metastatic lesions in CNS or in brain cannot be used for target lesions.
• Brain metastases may be allowed if patient’s condition is stable, defined as clinically asymptomatic, no requirement for high dose or increasing dose of systemic corticosteroids, and no need for any anticonvulsant therapy for metastatic brain disease. For the patient who has had radiation therapy, sequential post-treatment MRI tests, at least 4-6 weeks apart, should show no increases in brain lesion size/volume within 4 weeks prior to the study.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 and has a life-expectancy of more than 6 months.
• 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 ≥ 3.0×10^9/L;
  • Absolute neutrophil count (ANC) must be ≥ 1.5×10^9/L;
  • Platelet count ≥ 100×10^9/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;
  • Creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault equation;
  • Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 30 days after the last dose of poziotinib;
  • Females of childbearing potential must have a negative pregnancy test within 30 days prior to enrollment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or who are surgically sterilized do not require this test.

Exclusion Criteria:

• Patient has:
  • All Cohorts: EGFR T790M;
  • Cohorts 1 to 5: EGFR exon 20 point mutation;
  • Cohort 7: EGFR Exon 19 deletion and L858R or HER2 T798I mutations, EGFR and HER2 Exon 20 insertion mutation.
• Patient has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation-selective tyrosine kinase inhibitor (TKI) prior to study participation. The currently approved TKIs (ie, erlotinib, gefitinib, afatinib, osimertinib) are not considered to be exon 20 insertion-selective and are permissible (Cohorts 1 to 4).
• Patient is concurrently receiving chemotherapy, biologics, immunotherapy for cancer treatment; systemic anti-cancer treatment or investigational treatment should not be used within 2 weeks; local radiation therapy for bone pain may be allowed.
• Patient has a 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.
• Patient has a high risk of cardiac disease, as determined by the Investigator, may undergo either echocardiogram (ECHO) or multi-gated acquisition (MUGA) during Screening and has a cardiac ejection fraction < 50%.
• Patient has had other malignancies within the past 3 years, except for stable non-melanoma skin cancer, fully-treated and stable, early-stage prostate cancer, or carcinoma in situ of the cervix or breast without need of treatment.
• Patient is confirmed to have clinically significant or recent acute gastrointestinal disease presenting as diarrhea and/or coloenteritis as a main symptom (ie, acute enteritis, malabsorption, or Common Terminology Criteria for Adverse Events (CTCAE, version 4.03) Grade 2 or above diarrhea due to other etiologies).
• Patient has an active Grade ≥ 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.
• Patient is unable to take drugs orally due to disorders or diseases that may affect gastrointestinal function, such as inflammatory bowel diseases (e.g., Crohn’s disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
• 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 known hypersensitivity to poziotinib or has a history of allergic reactions attributed to chemically similar compounds or other tyrosine kinase inhibitors (TKIs).
• Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would not be appropriate for this study.
• 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.
• Patient is pregnant or breast-feeding.
• Cohort 5 only: Patient is eligible for treatment in an open cohort (Cohorts 1 to 4).