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: on-Small Cell Lung Cancer, Locally Advanced or Metastatic, with EGFR or HER2 Exon 20 Insertion Mutation
MedDRA version: 20.0Level: LLTClassification code 10066490Term: Progression of non-small cell lung cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-001868-36-FR

Lead Sponsor: Spectrum Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 174

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.
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 165
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 9

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.

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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