Fulvestrant, Palbociclib and Erdafitinib in ER+/HER2-/FGFR-amplified Metastatic Breast Cancer

Inclusion Criteria:

* Patients must be able to swallow and retain oral medication
* Patients must be ≥ 18 years of age
* Female patients of no childbearing potential must be post-menopausal. Postmenopausal female subjects should be defined prior to protocol enrollment by any of the following:
* Participants at least 60 years of age; OR
* Participants under 60 years of age and naturally (spontaneous, no alternative pathologic or physiological cause) amenorrhea for at least 12 months; OR
* Medical ovarian failure confirmed by follicle-stimulating hormone (FSH) and estradiol levels in the post menopausal range per local institutional normal range; OR
* Prior bilateral oophorectomy; OR
* Prior radiation castration with amenorrhea for at least 6 months; OR
* Treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (such as goserelin acetate or leuprolide acetate) is permitted for induction of ovarian suppression as long as it has been initiated at least 28 days prior to study enrollment
* Patients must have ECOG performance status 0 - 1
* Patients must have clinical stage IV or inoperable locoregional recurrent invasive mammary carcinoma that is:
* ER+ and/or PgR+ (≥ 1% positive stained cells) by immunohistochemistry (IHC)
* HER2-negative (by IHC or FISH, per ASCO guidelines)
* FGFR1 - 4 amplified
* Patients must have evaluable (may have either measurable or non-measurable) disease
* Patients must have available tissue for FGFR determination
* Patients must have had at least one line of therapy in the metastatic setting
* Current use of any of the drugs listed on the Cautionary Concomitant Med list has to be approved by the Study Chair
* Patients must have adequate hematologic, hepatic and renal function. All laboratory tests must be obtained within 2 weeks from study drug initiation. These include:
* ANC ≥ 1,500/mm3
* Platelet count ≥ 100,000/mm3
* HgB ≥ 9.0 g/dL
* Creatinine clearance ≥ 40 mL/min/1.73 m2
* SGOT, SGPT ≤ 2.5 x ULN if no liver metastasis present; SGOT, SGPT ≤ 4 x ULN if liver metastasis present
* Albumin ≥ 2.0 g/dL
* Total serum bilirubin ≤ 1.5 x ULN (≤ 3 x ULN or direct bilirubin ≤ 1.5 x ULN if known Gilbert's syndrome)
* Potassium within institutional normal limits
* Phosphorus ≤ institutional upper limit of normal

Exclusion Criteria:

* Prior use of an FGFR inhibitor
* More than 2 lines of chemotherapy in the metastatic setting. No limit on endocrine therapy lines. Prior exposure to CDK4/6 inhibitor acceptable.
* Radiation therapy ≤ 2 weeks prior to study entry. Patients who have received prior radiotherapy must have recovered from toxicity (≤ grade 1) induced by this treatment (except for alopecia)
* Prior cancer therapy (except for endocrine therapy) must have been discontinued for 1 week prior to initiation of study drugs
* Concurrent anti-cancer therapy other than the ones specified in the protocol is not permitted during study participation. Bisphosphonates or denosumab are allowed
* Major surgery within 4 weeks of enrollment
* Herbal preparations are not allowed throughout the study, and should be discontinued 14 days prior to initiation of study treatment
* Any corneal or retinal abnormality likely to increase the risk of eye toxicity, such as:
* Current corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration
* Uncontrolled glaucoma despite standard of care therapy
* Diabetic retinopathy with macular edema
* Known active wet, age-related macular degeneration (AMD)
* Known central serous retinopathy (CSR) or retinal vascular occlusion (RVO)
* Uncontrolled intercurrent illness including, but not limited to:
* Malabsorption syndrome significantly affecting gastrointestinal function
* Ongoing or active infection requiring antibiotics/antivirals
* Impairment of lung function (COPD \> grade 2, lung conditions requiring oxygen therapy)
* Symptomatic congestive heart failure
* Unstable angina pectoris, angioplasty, stenting, or myocardial infarction within 6 months
* Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment \[National Cancer Institute -Common Terminology Criteria for Adverse Events, Version 4.03, grade 3\]
* QTcF ≥ 480 msec on screening EKG
* Known history of clinically significant QT/QTc prolongation or Torsades de Pointes(TdP)
* ST depression or elevation of ≥ 1.5 mm in 2 or more leads
* Diarrhea of any cause ≥ CTCAE grade 2 that does not resolve within a few days when adequately treated with anti-diarrhea medications
* Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
* Symptomatic brain metastases (patients with a history of brain metastases must be clinically stable for more than 4 weeks from completion of radiation treatment and be off steroids)
* Known history of chronic liver or chronic renal failure
* Poor wound healing capacity