CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer

Inclusion Criteria:

• Patients with platinum-sensitive recurrent ovarian, fallopian or primary peritonealcancer (defined as recurrent disease > 6 months after completing last platinum-based chemotherapy) that are eligible to receive platinum-based chemotherapy).

• Documented disease recurrence/progression based on GCIG-RECIST

• Must have had at least 1 prior line of platinum-based therapy, prior bevacizumab orPARPi use are allowed. Women with germline BRCA mutations should be considered forPARPi maintenance as standard of care treatment prior to consideration of clinicaltrial enrollment

• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 with lifeexpectancy of ≥ 3months

• Adequate organ function

• Serum creatinine ≤1.5mg/dL or 24-hour clearance ≥50mL/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 xULN 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 sodiumwithin normal limits for the institution or corrected to within normal limitswith supplements before first dose of study medication

• Must be able to swallow CPI-0209 tablet/oral suspension

• Able to provide informed consent and comply with all study protocol

• Treated CNS metastasis allowed if treatment is completed ≥8 weeks prior toenrollment. Patients must be asymptomatic off systemic corticosteroids for at least 4 weeks after completion of radiation therapy. CNS disease must be stable orregressed on repeat imaging performed at least 4 weeks after completion of therapy.

• Women of child-bearing potential (those who have had a menstrual cycle within thelast year and have not had a tubal ligation or surgical removal of both ovariesand/or hysterectomy) must agree to abstain from vaginal intercourse or use andcontinue highly effective methods of contraception for at least 183 days afterdiscontinuation of study treatment.

• Total abstinence when this is in line with the preferred and usual lifestyle ofthe patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods ofcontraception.

• Female sterilization (have had surgical bilateral oophorectomy with or withouthysterectomy), total hysterectomy, or tubal ligation at least six weeks beforetaking study treatment. In case of oophorectomy alone, only when thereproductive status of the woman has been confirmed by follow-up hormone levelassessment.

• Male sterilization (at least 6 months prior to screening). The vasectomizedmale partner should be the sole partner for that patient.

• Use of oral, injected or implanted hormonal methods of contraception orplacement of an intrauterine device (IUD) or intrauterine system (IUS), orother forms of hormonal contraception that have comparable efficacy (failurerate <1%), for example hormone vaginal ring or transdermal hormonecontraception.

• In case of use of oral contraception, women should have been stable on the samepill for a minimum of 3 months before taking study treatment.

Exclusion Criteria:

• Borderline or low malignant potential histology

• Platinum-resistant disease (as defined as progressive disease (PD) within 6 monthsof completion of chemotherapy with a platinum agent).

• Known hypersensitivity to any of the excipients of CPI-0209.

• Gastrointestinal (GI) dysfunction or disease that may significantly alter theabsorption of the study drugs

• Concurrent malignancy or malignancy within 3 years prior to starting study drug withthe exception of adequately treated basal or squamous cell carcinoma,non-melanomatous skin cancer or curatively resected cervical cancer or per physiciandiscretion that the previous cancer was adequately treated with curative intent andunlikely to recur (the study PI must concur with this determination).

• History of HIV infection

• Has an active infection requiring systemic treatment

• Patient has any other concurrent severe and/or uncontrolled medical condition thatwould, in the investigator's judgment, cause unacceptable safety risks andcontraindicate patient's participation in the clinical study or compromisecompliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis,active untreated or uncontrolled fungal, bacterial or viral infections, significantcardiac/pulmonary disease etc.)

• Patient is currently receiving warfarin or other coumadin-derived anticoagulant fortreatment, prophylaxis or otherwise. Therapy with heparin, low molecular weightheparin (LMWH) or fondaparinux is allowed.

• Use of herbal supplements unless discontinued ≥7 days prior to initiation of studydrug

• Consumption of foods which are strong inducers or inhibitors of CYP3A4/5 has to bediscontinued 7 days prior to initiation of study drug. Patients that are unwillingto exclude Seville oranges, grapefruit juice, AND grapefruit from the diet and allfoods that contain those fruits from time of enrollment to through the duration ofstudy participation will be excluded.

• Pregnant or breast feeding

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

• Patient who has received radiotherapy ≤4 weeks or limited field radiation forpalliation ≤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.

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

• Patient has not recovered from all toxicities related to prior anticancer therapiesto NCI-CTCAE version 5 Grade ≤1 (Exception to this criterion: patients with anygrade of alopecia, controlled endocrine toxicities and/or neuropathy ≤ grade 2 areallowed to enter the study).

• Grade 3 baseline neuropathy

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