Ribociclib (Ribociclib (LEE-011)) With Platinum-based Chemotherapy in Recurrent Platinum Sensitive Ovarian Cancer

Inclusion Criteria:

1. Women ≥18 years old with platinum-sensitive recurrent ovarian, fallopian or primary
peritoneal cancer (defined as recurrent disease >6 months after completing last
platinum-based chemotherapy) eligible to receive platinum-based doublet chemotherapy.

2. Must have had at least 1 prior line of platinum-based therapy

3. ECOG 0-1 with life expectancy of ≥ 3 months

4. Adequate organ function:

- Serum creatinine ≤1.5mg/dL or 24-hour clearance ≥50 mL/min

- AST/ALT <2.5x ULN (or <5x ULN if liver metastasis are present)

- Total bilirubin ≤ULN or total bilirubin ≤3.0 x ULN or direct bilirubin ≤1.5 x ULN
in patients with well-documented Gilbert's Syndrome.

- Hemoglobin ≥9 gm/dl, Platelets ≥100,000/µL, ANC ≥1500/µL

- INR ≤1.5

- Potassium, total calcium (corrected for serum albumin), magnesium, and sodium
within normal limits for the institution or corrected to within normal limits
with supplements before first dose of study medication

5. Screening ECG (defined as the mean of the triplicate ECGs) with QTcF interval at
screening ≤450msec (using Fridericia's correction) and resting heart rate 50-90bpm

6. Must be able to swallow ribociclib (LEE-011) tablet/capsule

7. Documented disease recurrence/progression based on GCIG-RECIST

8. Able to provide informed consent and comply with all study protocols

9. Treated CNS metastasis allowed if treatment is complete ≥8 weeks prior to enrollment.
Patients must be asymptomatic off systemic corticosteroids for at least 4 weeks after
completion of radiation therapy. CNS disease must be stable or regressed on repeat
imaging performed at least 4 weeks after completion of therapy.

10. Women of child-bearing potential (those who have had a menstrual cycle within the last
year and have not had a tubal ligation or surgical removal of both ovaries and/or
hysterectomy) must agree to abstain from vaginal intercourse or use and continue
highly effective methods of contraception for 3 weeks after discontinuation of study
treatment.

11. Patients must have histologically confirmed malignancy that is metastatic or
unresectable and for which standard curative or palliative measures do not exist or
are no longer effective.

Exclusion Criteria:

1. Borderline or low-malignant potential histology.

2. Platinum-resistant disease (as defined as progressive disease within 6 months of
completion of chemotherapy with a platinum agent)

3. Grade 3 baseline neuropathy.

4. Known hypersensitivity to any of the excipients of ribociclib (LEE-011), including
peanuts and soy

5. Prior use of CDK4/6 inhibitors.

6. Congenital long QT syndrome or family history of unexpected sudden cardiac death

7. Concurrent malignancy or malignancy within 3 years prior to starting study drug, with
the exception of adequately treated basal or squamous cell carcinoma, non-melanomatous
skin cancer or curatively resected cervical cancer

8. Impairment of gastrointestinal (GI) function or disease that may significantly alter
the absorption of the study drugs

9. History of HIV infection

10. Patient has any other concurrent severe and/or uncontrolled medical condition that
would, in the investigator's judgment, cause unacceptable safety risks and
contraindicate patient's participation in the clinical study or compromise compliance
with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, active
untreated or uncontrolled fungal, bacterial or viral infections, etc.).

11. Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormalities, including any of the following:

a. Heart Association functional classification III-IV) b. Documented cardiomyopathy c.
Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated
acquisition (MUGA) scan or echocardiogram (ECHO) at screening d. Clinically
significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle
branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and
third-degree AV block) e. Long QT syndrome or family history of idiopathic sudden
death or congenital long QT syndrome, or any of the following: i. Risk factors for
Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesaemia, history
of cardiac failure, or history of clinically significant/symptomatic bradycardia.

ii. Concomitant use of medication(s) with a known risk to prolong the QT interval
and/or known to cause Torsades de Pointe that cannot be discontinued (within 5
half-lives or 7 days prior to starting study drug) or replaced by safe alternative
medication iii. Inability to determine the QT interval on screening (QTcF using
Fridericia's correction) f. Systolic blood pressure (SBP) >160 mmHg or <90 mmHg at
screening g. History of acute coronary syndromes (including myocardial infarction,
unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting)
or symptomatic pericarditis within 6 months prior to screening

12. Use of prohibited medications (see section 5.3) that cannot be changed to an
alternative therapy

13. Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior
to starting study drug, or who have not fully recovered from side effects of such
treatment.

a. The following uses of corticosteroids are permitted: single doses, topical
applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways
diseases), eye drops or local injections (e.g., intra-articular)

14. Patient is currently receiving warfarin or other coumadin-derived anticoagulant for
treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight
heparin (LMWH) or fondaparinux is allowed.

15. Use of herbal supplements unless discontinued ≥7 days prior to initiation of study
drug

16. Consumption of foods which are strong inducers or inhibitors of CYP3A4/5 has to be
discontinued 7 days prior to initiation of study drug

17. Pregnancy or lactation

18. Participation in a prior investigational study within 30 days prior to enrollment or
within 5 half-lives of the investigational product, whichever is longer

19. Patient who has received radiotherapy ≤4 weeks or limited field radiation for
palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade 1
or better from related side effects of such therapy (exceptions include alopecia)
and/or in whom ≥25% of the bone marrow (Ellis, 1961) was irradiated.

20. Patient has had major surgery within 14 days prior to starting study drug or has not
recovered from major side effects (tumor biopsy is not considered as major surgery).

21. Patient has not recovered from all toxicities related to prior anticancer therapies to
NCI-CTCAE version 5 Grade ≤1 (Exception to this criterion: patients with any grade of
alopecia and/or neuropathy ≤ grade 2 are allowed to enter the study).

22. Patient with a Child-Pugh score B or C.