Exemestane in Post-Menopausal Women With NSCLC

Inclusion Criteria

- Recurrent or progressive advanced stage non-small cell lung cancer (no small cell
component) with most recent treatment being an FDA approved immune checkpoint
inhibitor (pembrolizumab, atezolizumab, or nivolumab) NOTE: Pathology reports
documenting the diagnosis of NSCLC are required to be reviewed to confirm outside
diagnosis

- Sufficient tumor tissue available from original diagnosis or subsequent biopsy for
analysis of estrogen receptor and aromatase - tumor block or a minimum of 5 unstained
slides

- Failed at least 1 prior FDA approved treatment for advanced NSCLC.

- Measureable disease by RECIST version 1.1 (Appendix III)

- Post-menopausal defined as

- Age ≥ 55 years and 1 year or more of amenorrhea

- Age < 55 years and 1 year or more of amenorrhea with an estradiol assay < 20
pg/mL

- Surgical menopause with bilateral oophorectomy

- ECOG performance status 0, 1 or 2

* Life expectancy of 3 months or more in the opinion of the enrolling investigator and
documented in the medical record

- Adequate organ function within 14 days of study enrollment defined as:

- Hematology:

- Absolute neutrophil count (ANC) ≥ 1500/mm³, Platelets ≥ 100,000/mm³,
Hemoglobin ≥ 8 g/dL

- International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT)/partial
thromboplastin time (PTT) within normal limits (WNL) of the institution

- Biochemistry:

- Total Bilirubin within normal institutional limits

- AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN), except if there
is known hepatic metastasis, wherein transaminases may be ≤ 5 x
institutional ULN.

- Serum creatinine ≤ 1.5 mg/dl or glomerular filtration rate > 50 ml/min

- Must have recovered to CTCAE v 4 Grade 1 or better from the acute effects of any prior
surgery, chemotherapy or radiation therapy. Chronic residual toxicity (i.e. peripheral
neuropathy) is permitted.

- A minimum time period must elapse between the end of a previous treatment and start of
study therapy:

- 1 week from the completion of radiation therapy for brain metastases

- 4 weeks from the completion of chemotherapy or any experimental therapy

- 4 weeks from prior major surgery (such as open biopsy or significant traumatic
injury)

- Voluntary written consent before any research related procedures or therapy

Exclusion Criteria

- Known active CNS disease - If patient has history of brain metastases, the brain
lesions must have been treated with radiation and/or surgery - patients should be
neurologically stable and requiring ≤10mg oral prednisone equivalence of steroids per
day

- Any toxicity from immune-related toxicity from prior immune therapy that would
preclude further treatment with anti-PD-1/PDL-1 inhibitor or ongoing IR toxicity ≥
Grade 2

- Requiring > 10 mg prednisone equivalence of steroids per day for immune-related
toxicity

- Inability or unwilling to swallow study drug

- Any gastrointestinal condition causing malabsorption or obstruction (eg, celiac sprue,
gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind
loop syndrome)

- Currently using hormone replacement therapy (oral or patch) or/and phytoestrogen
supplements (i.e. black cohosh)

- Known hypersensitivity to exemestane or its excipients

- Any serious underlying medical condition that, in the opinion of the enrolling
physician, would impair the ability of the patient to receive protocol treatment

- Prior malignancy, with the exception of curatively treated squamous cell or basal
carcinoma of the skin or in situ cervical cancer, unless there is a 3-year
disease-free interval

- Concomitant use of strong CYP3A4 inducers such as rifampicin, phenytoin,
carbamazepine, phenobarbital, or St. John's wort as these may significantly reduce the
availability of exemestane