Study of the Pan-ERBB Inhibitor Neratinib Given in Combination With Everolimus, Palbociclib or Trametinib in Advanced Cancer Subjects With EGFR Mutation/Amplification, HER2 Mutation/Amplification, HER3/4 Mutation or KRAS Mutation

Inclusion Criteria:

1. Subjects with advanced or metastatic solid tumors that are refractory to standard
therapies known to provide clinical benefit. Subjects with hematologic malignancy
including lymphoma/myeloma will not be enrolled on this study.

2. Subjects must have one of the following: a. somatic mutations in human epidermal
growth factor receptor (EGFR, HER2, HER3, and HER4); b. EGFR gene amplification
(patients with 3+ results on immunohistochemistry testing for EGFR may be allowed to
enroll if gene amplification results are unavailable); c. HER2 gene amplification
(patients with 3+ results on immunohistochemistry testing for Her-2 may be allowed to
enroll if gene amplification results are unavailable); d. Somatic mutation in KRAS
(Patients will be enrolled only on neratinib and trametinib combination ARM).

3. Subjects must have measurable disease by RECIST v1.1.

4. Subjects must be >/=18 years of age.

5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.

6. Abnormal organ function is permitted. However, subjects must have: a. absolute
neutrophil count >/= 1500/mL; b. platelets >/= 100,000/mL; c. hemoglobin >/= 9 g/dL;
d. creatinine f. aspartate aminotransferase (AST/SGOT) and/or alanine aminotransferase (ALT/SGPT)

7. Subjects must be >/=4 weeks beyond treatment with any chemotherapy or other
investigational therapy to include hormonal, biological, or targeted agents; or at
least 5 half-lives from hormonal, biological, or targeted agents, whichever is shorter
at the time of treatment initiation.

8. Women of child-bearing potential MUST have a negative serum or urine human chorionic
gonadotropin (HCG) test unless prior hysterectomy or menopause (defined as 12
consecutive months of amenorrhea). Subjects should not become pregnant or breastfeed
while on this study. Sexually active subjects must agree to use contraception for the
duration of study participation and for 4 months after the last dose of neratinib and
everolimus, palbociclib or trametinib.

9. Ability to understand and willingness to sign informed consent form prior to
initiation of the study and any study procedures.

10. Only for subjects enrolled in Arm 1 - Neratinib and Everolimus: Fasting lipid profile:
Cholesterol less than or equal to 350 mg/dL and triglycerides less than or equal to
400 mg/dL.

11. Only for subjects enrolled in Arm 1 - Neratinib and Everolimus: Patients who are
taking medications with moderate or potent inhibitors or inducers of CYP450 3A4 should
be off for 5 half-lives prior to starting everolimus.

12. Only for subjects enrolled in Arm 2 - Neratinib and Palbociclib : Any prior neuropathy
should be back to baseline or grade 1

13. Only for subjects enrolled in Arm 2 - Neratinib and Palbociclib : Patients who are
taking medications with moderate or potent inhibitors or inducers of CYP450 3A4 should
be off for 5 half-lives prior to starting Palbociclib.

14. Only for subjects enrolled in Arm 3 - Neratinib and Trametinib: All skin rash
(dermatitis acneiform, erythema, xeroderma, eczema) should be at grade 1 when starting
trametinib treatment.

15. Only for subjects enrolled in Arm 3 - Neratinib and Trametinib: History of retinal
disorder, dry eye syndrome, or blurry vision need to be evaluated by ophthalmology
prior to starting treatment.

Exclusion Criteria:

1. Subjects who are pregnant or breastfeeding;

2. Known Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV) infection.

3. Inability or unwillingness to swallow pills.

4. Active infection requiring intravenous (IV) antibiotics or other uncontrolled
intercurrent illness requiring hospitalization.

5. Clinically significant gastrointestinal (GI) abnormalities that may alter absorption
such as malabsorption syndrome or major resection of the stomach or bowels. For
example, subjects should have no more than 50% of the large intestine removed and no
sign of malabsorption (e.g. gastrectomy, ileal bypass, chronic diarrhea, Crohn's
disease, malabsorption, gastroparesis).

6. Inability to comply with the study and follow-up procedures.

7. History of cerebrovascular accident (CVA), myocardial infarction or unstable angina
within the previous 6 months before starting therapy.

8. Prolongation of QT/QTc interval (QTc interval >450 ms for males or >470 ms for
females) using the Fredericia method of QTc analysis

9. Has known primary brain tumor, active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may
participate provided they are clinically stable with no neurological symptoms, and are
not using steroids for at least 7 days prior to trial treatment. This exception does
not include carcinomatous meningitis which is excluded regardless or clinical
stability.

10. Uncontrolled concurrent disease or illness including but not limited to: - symptomatic
congestive heart failure (NYHA Class III or IV) per the NYHA Classification (see
Appendix B), unstable angina pectoris, clinically significant cardiac arrhythmia; -
unstable or untreated cardiac conditions or ejection fraction of <50% as determined by
echocardiogram (ECHO) or multiple gated acquisition scan (MUGA); - diabetes mellitus
(i.e. fasting blood glucose >220 despite acceptable chronic diabetes therapy); -
psychiatric illness that would limit compliance with study requirements, as determined
by the investigator

11. Participating in any other clinical trials using an investigational product.

12. Only for subjects enrolled in Arm 1 - Neratinib and Everolimus: History of
hypersensitivity to everolimus

13. Only for subjects enrolled in Arm 1 - Neratinib and Everolimus: Subjects requiring
therapy with immunosuppressive agents such as anti-tumor necrosis factor alpha (TNFa)
agents (Etanercept, Adalimumab), azathioprine, methotrexate, cyclosporine, etc for
active autoimmune disorder.

14. Only for subjects enrolled in Arm 1 - Neratinib and Everolimus: Major surgery days prior to treatment with everolimus.

15. Only for subjects enrolled in Arm 3 - Neratinib and Trametinib: Albumin less than 3
Gm/dL