| Eligibility |
Inclusion Criteria:
- Histologically or cytologically confirmed stage IV or recurrent solid tumor not
amenable to curative intent therapy
- Cohort 1 specific inclusion criteria: NSCLC with documented EGFR exon 20 mutation by
one of the following Clinical Laboratory Improvement Act (CLIA) certified tests:
OncoMine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne
Assay or by a Food and Drug Administration (FDA) approved device using cobas EGFR
mutation test version (v)2 or therascreen EGFR RGQ PCt kit; Mutations include
D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH, or any other exon
20 in-frame insertion or point mutation excluding T790M
- Cohort 2 specific inclusion criteria: NSCLC with documented HER2 exon 20 mutation by a
CLIA certified tests: Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using
plasma), or FoundationOne Assay; eligible mutations include A775_G776insYVMA,
G776_V777insVC, or P780_Y781insGSP, or any other in-frame exon 20 insertion mutation
or point mutation including, but not limited to, L755S, G776V, and V777L
- Cohort 3 specific inclusion criteria: NSCLC with documented EGFR exon 20 mutation
(excluding T790M) by one of the following CLIA certified tests: OncoMine Comprehensive
Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne Assay or by an FDA
approved device using cobas EGFR mutation test v2 or therascreen EGFR RGQ PCt kit;
mutations include D770_N771insSVD, D770_N771insNPG, V769_D770insASV, H773_V774insNPH,
or any other exon 20 in-frame insertion or point mutation excluding T790M
- Cohort 4 specific inclusion criteria: solid tumor (excluding NSCLC) harboring EGFR or
HER2 exon 20 mutations documented by one of the following CLIA certified tests:
Oncomine Comprehensive Assay (OCA), Guardant360 Assay (using plasma), or FoundationOne
Assay
- Cohort 5 specific inclusion criteria: solid tumor harboring HER2 exon 19 mutation
documented by one of the following CLIA certified tests: Oncomine Comprehensive Assay
(OCA), Guardant360 Assay (using plasma), or FoundationOne Assay
- Patients must have exhausted all FDA-approved standard of care options for locally
advanced or metastatic disease, or are ineligible for FDA-approved standard of care
options, or refusing to receive FDA-approved standard of care options. Previously
untreated patients are allowed only in cohort 1 and 3 and are eligible only if EGFR
Exon 20 mutation is confirmed using an FDA approved device/test such as cobas EGFR
Mutation Test v2, therascreen EGFR RGQ PCR Kit or other FDA tests prior to study
enrollment
- 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
- Measurable disease by RECIST 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Ability to take pills by mouth
- Leukocytes >= 3,000/mcL
- Absolute neutrophil count >= 1,500/mcL
- Platelets >= 100,000/mcL
- Hemoglobin >= 9.0 g/dL
- Total bilirubin =< 2 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
=< 2.5 institutional upper limit of normal of =< 5 x ULN if liver metastases are
present
- Alkaline phosphatase =< 2.5 institutional upper limit of normal of =< 5 x ULN if liver
metastases are present
- Creatinine clearance >= 50 mL/min/1.73 m^2 by Cockcroft-Gault equation
- Brain metastases are allowed, as long as they are stable and do not require treatment
with anticonvulsants or escalating doses of steroids
- Females of childbearing potential must have a negative serum or urine pregnancy test
and must agree to use adequate contraception for the duration of the study and six
months after; adequate contraception methods include: birth control pills (e.g.
combined oral contraceptive pill), barrier protection (e.g. condom plus spermicide,
cervical/vault cap or intrauterine device), and abstinence; females of childbearing
potential are defined as those who are not surgically sterile (i.e., bilateral tubal
ligation, bilateral oophorectomy, or complete hysterectomy) or postmenopausal (defined
as 12 months with no menses without an alternative medical cause); women will be
considered post-menopausal if they have been amenorrheic for the past 12 months
without an alternative medical cause
- The following age-specific requirements must also apply:
- Women < 50 years old: they would be considered post-menopausal if they have been
amenorrheic for the past 12 months or more following cessation of exogenous
hormonal treatments; the levels of luteinizing hormone (LH) and
follicle-stimulating hormone (FSH) must also be in the post-menopausal range (as
per the institution)
- Women >= 50 years old: they would be considered post-menopausal if they have been
amenorrheic for the past 12 months or more following cessation of all exogenous
hormonal treatments, or have had radiation-induced oophorectomy with the last
menses > 1 year ago, or have had chemotherapy-induced menopause with > 1 year
interval since last menses, or have had surgical sterilization by either
bilateral oophorectomy or hysterectomy
- Non-sterilized males who are sexually active with a female partner of childbearing
potential must use adequate contraception for the duration of the study and 90 days
after the last dose of study medication; adequate contraception methods include: birth
control pills (e.g. combined oral contraceptive pill), barrier protection (e.g. condom
plus spermicide, cervical/vault cap or intrauterine device), and abstinence
- Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria:
- EGFR T790M mutation or any other acquired EGFR exon 20 mutation; patients with
coexisting primary EGFR exon 20 and T790M mutations are eligible
- Have received or are receiving an investigational medicinal product (IMP) or other
systemic anticancer treatment within 2 weeks prior to the first dose of study
treatment
- Any concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer
treatment
- Have known or suspected brain metastases or spinal cord compression, unless the
condition has been asymptomatic, has been treated with surgery and/or radiation, and
has been stable without requiring escalating corticosteroids nor anti-convulsant
medications for at least 4 weeks prior to the first dose of study medication
- Known hypersensitivity to poziotinib or history of allergic reactions attributed to
compounds of similar chemical or biologic composition to poziotinib
- Cardiac conditions as follows:
- 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 cardiac ejection fraction < 50% by either echocardiogram or
multi-gated acquisition (MUGA) scan
- Have any unresolved chronic toxicity with Common Terminology Criteria for Adverse
Events (CTCAE) version 4.03 grade >= 2, from previous anticancer therapy, except for
alopecia
- 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
- Have any condition or illness that, in the opinion of the investigator, might
compromise patient safety or interfere with the evaluation of the safety of the drug
- Pregnant or breastfeeding women
- History of another primary malignancy within 2 years prior to starting study
treatment, except for adequately treated basal or squamous cell carcinoma of the skin
or cancer of the cervix in situ
- Recent major surgery within 4 weeks prior to starting study treatment, with the
exception of surgical placement for vascular access
- Male or female patients of reproductive potential who are not employing an adequate
method of birth control; adequate contraception methods include: birth control pills
(e.g. combined oral contraceptive pill), barrier protection (e.g. condom plus
spermicide cervical/vault cap or intrauterine device), and abstinence
- Uncontrolled intercurrent illness including, but not limited to, uncompensated
respiratory, cardiac, hepatic, or renal disease, active infection (including hepatitis
B, hepatitis C, human immunodeficiency virus [HIV], and active clinical tuberculosis),
or renal transplant; ongoing or active infection, symptomatic congestive heart
failure, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or
gastritis, or psychiatric illness/social situations that would limit compliance with
study requirements
- Active bleeding disorders.
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