Study of COTI-2 as Monotherapy or Combination Therapy for the Treatment of Malignancies

Inclusion Criteria

• •1. ≥18 years of age.
• •2. Willing and able to provide written informed consent to participate in this investigational study.
• •3. Cancer that is recurrent, metastatic, or unresectable and for which no effective or curative measures exist.
• •* Part 1: Ovarian, fallopian tube, primary peritoneal, endometrial, or cervical cancer
• •* Part 2: HNSCC, with confirmed p53 mutations
• •* Part 3: Gynecological malignancies, HNSCC, colorectal, lung, pancreatic cancer, or other tumors with Sponsor approval.
• •4. Ability to attend all scheduled study visits
• •5. Measurable disease by physical examination or imaging as defined by RECIST v1.1 criteria or evaluable disease as defined by Gynecologic Cancer Intergroup (GCIG) CA125 criteria.
• •6. European Cooperative Oncology Group (ECOG) performance status 0 or 1.
• •7. Life expectancy ≥3 months.
• •8. Adequate bone marrow, liver, renal, and cardiac function at study entry, assessed as follows:
• •* Hemoglobin ≥9.0 g/dL;
• •* Absolute neutrophil count (ANC) ≥1.5 x 109/L;
• •* Platelet count ≥100 x 109/L;
• •* Prothrombin time (PT) or international normalize rate (INR) within 1.5x upper limit of normal;
• •* Partial thromboplastin time (PTT) within 1.5x upper limit of normal;
• •* Total bilirubin within normal limits;
• •* Alanine transaminase (ALT) and aspartate transaminase (AST) within 1.5x upper limit of normal;
• •* Calculated creatinine clearance \>50 mL/min;
• •* Urine protein \<500 mg or urine protein: creatinine ratio (UPC) \<1.0; and
• •* Left ventricular ejection fraction (LVEF) ≥55% (or the institutional lower limit of normal \[LLN\]) as evidenced on ECHO.
• •9. Prior chemotherapy, other investigational agents, or radiation must be discontinued for at least 28 days prior to the first administration of COTI-2. Hormone treatments must be discontinued for at least 28 days prior to the first administration of COTI-2.
• •10. Toxicity from prior therapy (except alopecia) has resolved to ≤Grade 1; in the event of toxicity that has not resolved to ≤Grade 1 but is considered stable, the patient may be eligible after discussion among the investigator and sponsor's medical monitor.
• •11. Physiologically incapable of becoming pregnant, postmenopausal, or negative pregnancy test and agree to use adequate contraception (e.g., oral contraceptive, double barrier method, intra-uterine device, intra-muscular contraceptive).
• •12. Patients enrolled in the expansion phase must be willing to undergo pre and post-Cycle 1 biopsies.
• •13. Patients enrolled in the escalation and expansion phases will be required to have archival tissue available for analysis.