Phase1 of Neratinib+Trastuzumab, Pertuzumab, Paclitaxel in Patients With Advanced Solid Tumors/HER2+

Inclusion Criteria:

* Women and men 18 years or older with advanced solid tumor malignancy
* Ability to understand and voluntarily sign informed consent prior to undergoing any study-related assessments or procedures, as well as adhere to the study visit schedule and other protocol requirements.
* Local histologic or cytologic confirmation of HER2+ solid tumors by FISH amplification or IHC (3+)
* Patients must have received one prior approved therapy for metastatic disease and have not curable options
* For escalation: Documentation by established staging studies or clinical examination to have measurable or non-measurable metastatic disease per RECIST v1.1 criteria.
* For expansion: Documentation by established staging studies or clinical examination to have measurable metastatic disease per RECIST v1.1 criteria.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
* Adequate organ function:
* Absolute neutrophil count (ANC) ≥ 1.5 X 109/L
* Hemoglobin (Hgb) ≥9g/dL
* Platelets (plt) ≥ 100 x 109/L
* Potassium within normal range, or correctable with supplements;
* Serum calcium and magnesium within the normal range (or corrected with supplements)
* AST and ALT ≤2.5 x Upper Limit Normal (ULN)
* Serum total bilirubin ≤ 1.5 x ULN
* Serum creatinine ≤ 1.5 x ULN, or 24-hr clearance ≥ 60ml/min
* Serum albumin \> 3.0 g/dL
* Left ventricular ejection fraction of \>55% (or institutional lower normal value)
* Females of child-bearing potential (FCBP) must have negative serum pregnancy test within 7 days before starting study treatment and willingness to adhere to acceptable forms or birth control (a physician- approved contraceptive method: oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner)

FCBP is defined as a sexually mature women who:

* Have not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or,
* Have not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time during the preceding 12 consecutive months
* Must be willing to practice abstinence or use highly effective contraception for a minimum of 6 months following completion of study treatment (in addition to during study therapy)
* Male subjects with female partner of childbearing potential must agree to the use of a physician-approved contraceptive method throughout the course of the study and for 3 months after the last dose of the investigational product.
* Ability to take oral medications

Exclusion Criteria:

* Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
* Any condition that confounds the ability to interpret data from the study.
* Patients must have recovered from side effects from prior cancer-directed therapy to grade 1 or less (unless deemed not clinically significant by study investigator).
* Symptomatic central nervous system metastases. Subjects with brain metastases that have been previously treated and are stable for 4 weeks are allowed.
* Persistent diarrhea or malabsorption ≥ NCI CTCAE grade 1, despite medical management, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.
* Unstable angina, significant cardiac arrhythmia, or New York Heart Association (NYHA) class III or IV congestive heart failure.
* Grade 2 or higher neuropathy
* Known history of: cardiac disease, heart failure or decreased left ventricular ejection fraction, significant clinical arrhythmias
* Prior systemic cancer-directed treatments or investigational modalities ≤ 5 half lives or 4 weeks, whichever is shorter, prior to starting study drug or who have not recovered from grade 2 or higher side effects of such therapy (except alopecia).
* Major surgery ≤ 2 weeks prior to starting a study drug or who have not recovered from side effects of such therapy.
* Known allergic reaction to neratinib, pertuzumab, trastuzumab, paclitaxel, or any of their components.
* Women who are pregnant or breast-feeding.
* Known active Human Immunodeficiency Virus (HIV) infection, Hepatitis B or C.