A Study of Poziotinib in Patients with Non-Small Cell Lung Cancer that has tested positive for Presence of EGFR or HER2 Exon 20 Insertion Mutation cells

Phase 1

Conditions: MedDRA version: 21.1Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
on-Small Cell Lung Cancer, Locally Advanced or Metastatic

Registration Number: EUCTR2018-001868-36-IT

Lead Sponsor: SPECTRUM PHARMACEUTICALS

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 603

Inclusion Criteria

1. Patient is at least 18 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. 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
4. 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
• 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: Either tissue or plasma samples must be provided after osimertinib progression.
• Cohort 7: Either tissue or plasma samples
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 530
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 73

Exclusion Criteria

1. 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
2. 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 and 2)
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; or 5 half lives , whichever is longer, 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 has a cardiac ejection fraction <50%.
6. 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
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 has an active Grade higher than 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 =2pneumonitis.
9. 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
10. 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)
11. Patient has known hypersensitivity to poziotinib or has a history of allergic reactions attributed to chemically similar compounds or other tyrosine kinase inhibitors (TKIs)
12. Patient has an active uncontrolled infection, underlying medical condition, or other serious illness that would not be appropriate for this study

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

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