A Phase 2 Study of Kevetrin in Subjects With Ovarian Cancer

This is an open label, dose-escalation trial to study the safety, biomarker changes
(including modulation of p53), objective tumor response changes, and pharmacokinetics
following administration of two different treatment regimens of Kevetrin over a 3-week period
to subjects with platinum-resistant/refractory ovarian cancer. Following the 3 weeks of
Kevetrin dosing, subjects are to be followed up for 3 weeks after completion of Kevetrin
treatment. Standard of care treatment, as medically appropriate and per local guidelines,
outside of this study protocol can commence after the collection of the post-Kevetrin
treatment biomarker samples (collected on Day 21±1 day). The patient population recruited
into this study includes those ovarian cancer patients that have platinum
resistant/refractory disease, defined as disease progression/relapse within 6 months
following the last administered dose of platinum therapy (resistant), or lack of response or
disease progression while receiving the most recent platinum based therapy (refractory),
respectively. Patients may or may not have had additional treatment (e.g., Doxil) prior to
entry in this study.

A total of approximately 10 study participants are planned to be enrolled in two cohorts of
approximately 5 subjects per cohort, with enrollment in a sequential, dose-escalating
fashion. Investigators and subjects will be aware of the treatment cohort into which they are
recruiting. Cohort details and the planned doses are:

Cohort 1 (n=5) Kevetrin Cycle - Kevetrin 250 mg/m2 IV per dose every other day (q.o.d.)/ 3
doses per week (750 mg/m2 per week), for 3 weeks (single cycle; total 9 doses); Follow-up for
3 weeks after Kevetrin treatment ends Cohort 2 (n=5) Kevetrin Cycle - Kevetrin 350 mg/m2 IV
per dose every other day (q.o.d.)/ 3 doses per week (1050 mg/m2 per week), for 3 weeks
(single cycle; total 9 doses); Follow-up for 3 weeks after Kevetrin treatment ends Cohorts 1
and 2 will be conducted in a sequential fashion, with safety data from cohort 1 evaluated by
an independent Data Monitoring Committee (DMC). The DMC will make appropriate recommendations
based on the available safety data as regards the intent of progressing to the higher dose
cohort 2.

Inclusion Criteria:

1. Evidence of a personally signed and dated written informed consent to participate in
the clinical study

2. Non-pregnant female adults at least 18 years of age at time of informed consent

3. Histologically confirmed serous epithelial ovarian cancer with peritoneal metastases

4. Platinum resistant/refractory disease, defined as disease progression/relapse within 6
months following the last administered dose of platinum therapy (resistant), or lack
of response or disease progression while receiving the most recent platinum based
therapy (refractory), respectively

5. Measurable disease, as determined by radiologist evaluator, with at least 1
unidimensional measurable lesion (target lesion) by RECIST v.1.1 that has not
previously been irradiated or biopsied

6. Presence of non-target lesions that have not previously been irradiated or biopsied;
to allow for collection of needle-biopsies at Screening and after completion of
Kevetrin treatment

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

8. Adequate hematologic and organ function as confirmed by laboratory values at
Screening:

1. Bone marrow function: Absolute neutrophil count (ANC) ≥ 1500 Cells/μL (with no
evidence that this ANC was induced or supported by granulocyte colony stimulating
factors)

2. Hemoglobin ≥ 9 g/dL (with no RBC transfusions within 7 days of Screening)

3. Platelets ≥ 100,000 cells/μL (with no evidence that this platelet count was
induced or supported by a platelet-stimulating agent)

4. Renal function: creatinine ≤ 1.5 x ULN

5. Hepatic function: total bilirubin ≤ 1.5 x ULN; ALT and AST ≤ 3 x ULN; alkaline
phosphatase ≤ 2.5 x ULN

6. Neurologic function: neuropathy (sensory and motor) ≤ CTCAE Grade 1

7. Coagulation status: prothrombin time (PT) ≤ 1.5 ULN or INR within normal limits;
and partial thromboplastin time (PTT) ≤ 1.2 × ULN

9. Women of child-bearing potential are required to use effective contraception
throughout the study period. Effective contraception methods include:

1. Total abstinence (if this is the usual lifestyle of the subject). Periodic
abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and
withdrawal are not acceptable methods of contraception. (Subject must agree to
use contraception should they become sexually active while on the study.)

2. Surgical sterilization (hysterectomy and/or bilateral oophorectomy) or tubal
ligation at least six weeks before start of study treatment.

3. Male partner sterilization, occurring at least 6 months prior to screening. For
female subjects on the study, the vasectomized male partner should be their sole
partner.

4. Double barrier method: Condom or Occlusive cap (diaphragm or cervical/vault caps)
with spermicidal foam/gel/film/cream/vaginal suppository.

5. Oral*/ injected/ implanted/ transdermal hormonal contraception or other forms of
hormonal contraception that have comparable efficacy (failure rate <1%), e.g.,
hormone vaginal ring.

6. Intrauterine device or intrauterine system. *Stable oral contraception use (on
the same pill) for a minimum of 3 months before taking study treatment.

Women are considered post-menopausal and not of child-bearing potential if they have
had 12 consecutive months of natural (spontaneous) amenorrhea with an appropriate
clinical profile (e.g., age appropriate, history of vasomotor symptoms) or have had
surgical hysterectomy and/or bilateral oophorectomy or tubal ligation at least six
weeks ago.

10. Estimated life expectancy of at least 6 months, in the Investigator's opinion

11. Willing and able to comply with scheduled visits, study assessments and laboratory
tests, and other study procedures

Exclusion Criteria:

1. Unwilling to allow removal of tumor biological samples for analysis, i.e., biopsies of
tumor lesions, and/or collection of ascites fluid from abdominal ascites (if present)

2. Non epithelial tumor, including malignant mixed Müllerian tumors without high grade
serous component, or ovarian tumors with low malignant potential (i.e., borderline
tumors)

3. Known presence of central nervous system metastases

4. Presence of tumor metastases causing significant pleural disease/effusion unilaterally
or bilaterally (significant pleural effusion is defined by need for thoracentesis more
frequently than once every 21 days)

5. Presence of ascites that requires paracentesis more frequently than once every 21
days.

6. A history of another primary cancer that has been active or treated within the past 3
years prior to start of study treatment, with the exception of adequately
treated/resected: basal cell or squamous cell skin carcinoma or actinic keratoses; or
carcinoma in situ of the breast or of the cervix; or non-invasive malignant colon
polyps

7. Persistent toxic effects with severity of CTCAE grade 2 or greater (excluding
alopecia) caused by previous treatment

8. History of arterial or deep venous thromboembolism within the 12 months prior to
enrollment

9. Clinically significant cardiac disease, including:

1. Myocardial infarction or unstable angina < 6 months prior to enrollment

2. New York Heart Association (NYHA) Grade II or greater congestive heart failure

3. Cardiac arrhythmia requiring medication (does not include asymptomatic atrial
fibrillation with controlled ventricular rate)

10. Electrocardiogram (ECG) obtained at Screening which shows QTc prolongation or other
medically relevant abnormalities which may affect subject safety or interpretation of
study results

11. At a higher than average risk, in the Investigator's opinion, of bowel perforation
(e.g., symptoms of partial or complete bowel obstruction, recent (within 6 months)
history of fistula or bowel perforation, requirement for total parenteral nutrition
and continuous hydration)

12. Active or chronic recurrent systemic infections that require continuous antimicrobial
therapy during the Kevetrin study period

13. Past medical history of infection with HIV, hepatitis B or hepatitis C

14. Ongoing or recent history of any other uncontrolled and/or clinically significant
systemic disease or condition which, in the Investigator's medical opinion, should
exclude participation in the study

15. Less than 3 weeks between major surgery and planned start of study treatment; major
incisions must have healed

16. Less than 4 weeks since last treatment for ovarian cancer

17. Any investigational or experimental therapy or procedure or participation in any
interventional trial within 4 weeks or 5 half-lives (whichever is longer) prior to
start of study treatment

18. Women of child-bearing potential who are pregnant or nursing (lactating)

19. Previous participation in a clinical study of Kevetrin

20. History of alcohol or substance abuse, unless in full remission for more than 6 months
prior to start of study treatment

21. Any other severe acute or chronic medical or psychiatric condition or test
abnormality(ies) that, in the Investigator's opinion, puts the subject at significant
risk, could confound the study results, or may interfere significantly with the
subject's participation in the study