E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non-Small Cell Lung Cancer, Locally Advanced or Metastatic, with EGFR or HER2 Exon 20 Insertion Mutation |
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E.1.1.1 | Medical condition in easily understood language |
Non-Small Cell Lung Cancer, Locally Advanced or Metastatic |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066490 |
E.1.2 | Term | Progression of non-small cell lung cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the Objective Response Rate (ORR) to poziotinib in patients with non-small cell lung cancer (NSCLC) with EGFR or HER2 (ErBB2) exon 20 insertion mutations |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives: •To evaluate other efficacy variables of poziotinib in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations, including the following: • Disease Control Rate (DCR) (complete response + partial response + stable disease) • Duration of Response (DoR) • To evaluate the safety and tolerability of poziotinib in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations Exploratory Objectives: • To evaluate Progression-free Survival (PFS) in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations who are treated with poziotinib • To evaluate the Quality of Life, before and after treatment, in patients with NSCLC with EGFR or HER2 exon 20 insertion mutations who are treated with poziotinib |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patient, or patient’s authorized representative, must be willing and capable of giving written Informed Consent and must be able to adhere to dosing and visit schedules as well as meet all study requirements 2. Patient has histologically or cytologically confirmed non-small cell lung cancer not amenable to curative intent therapy or stage IV NSCLC 3. Specific mutations: • Cohort 1: Documented EGFR exon 20 insertion mutation using an FDA-approved in vitro diagnostic test (ie, cobas® EGFR mutation test v2 or therascreen EGFR RGQ PCR kit), a CLIA certified test (for US sites) (eg, OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay), or similarly accredited test (for ex-US sites) for tissue or plasma • Cohort 2: Documented HER2 exon 20 insertion mutation using a CLIA certified test (for US sites) (eg, OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay) or similarly accredited test (for ex-US sites) for tissue or plasma 4. 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 prior to the study 5. Brain metastases are allowed, as long as they are stable and do not require treatment with anticonvulsants or escalating doses of steroids 6. Patient has had at least one prior systemic therapy for metastatic disease 7. Patient is at least 18 years of age 8. Patient has measurable disease, as per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) 9. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 10. 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 • Aspartate aminotransferase/serum glutamic-oxaloacetic transaminase (AST/SGOT), alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT), and gamma-glutamyltransferase (GGT) ≤2.5×upper limit of normal (ULN); if hepatic metastases are present, ≤5.0×ULN • Creatinine clearance ≥50 mL/min 11. 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 12. 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. |
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E.4 | Principal exclusion criteria |
1. Patient has EGFR T790M mutation or other acquired EGFR exon 20 point mutation 2. Patient has had previous treatment with poziotinib or any other EGFR or HER2 exon 20 insertion mutation tyrosine kinase inhibitor prior to study participation. 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; local radiation therapy for bone pain may be allowed. 4. 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 5. 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 if the patient has a cardiac ejection fraction <50%, the patient will be excluded. 6. Patient has a history of other malignancies within the last 5 years, except for non-melanoma skin cancer or carcinoma in situ of the cervix 7. 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) 8. 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 9. 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) 10. Patient has known hypersensitivity to poziotinib or history of allergic reactions attributed to compounds of similar chemical or biologic composition to poziotinib 11. Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would impair the ability of the patient to receive protocol treatment 12. Patient has active bleeding disorders, uses warfarin or other coumadin-derived anticoagulants, has abnormal International Normalized Ratio (INR), or abnormal prothrombin time test within one month prior to the study 13. Patient has had recent major surgery within 15 days prior to starting study treatment, with the exception of surgical placement for vascular access 14. Patient is pregnant or breast-feeding. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Objective Response Rate (ORR, the rate of complete response and partial response) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ORR is defined as the best response recorded from the start of the study until the end of study in patients who received at least 1 dose of poziotinib. The ORR will be based on the primary analysis population. The ORR will be determined by an independent radiologic review committee. |
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E.5.2 | Secondary end point(s) |
• Disease Control Rate (DCR, the rate of complete response, partial response, and stable disease) • Duration of Response (DoR) • Safety |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
DCR will be assessed from the first dose of poziotinib to the end of study. DoR will be measured from the date that measurement criteria are first met for CR-complete response or PR-partial response (whichever status is recorded first) until the first subsequent date that progressive disease or death is documented. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
France |
Italy |
Netherlands |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |