Chk2 Inhibitor for Recurrent EpitheliAl periToneal, fallopIan or oVarian cancEr (CREATIVE Phase IA Trial) (CREATIVE)

This is an interventional treatment trial for Platinum-resistant Ovarian Cancer focused on measuring PHI-101, Chk2 inhibitor, antineoplastic, Platinum-resistant Ovarian Cancer Read More

Inclusion Criteria:

1. Females aged ≥ 19 years at the time of informed consent

2. Pregnancy (childbearing potential and planning a pregnancy) and breast-feeding status ① Women of non-childbearing potential, women who are not pregnant or breast-feeding, or women who are not planning a pregnancy during the study

   ② Women of childbearing potential (Section 10.3.2.7.1) who have a confirmed negative pregnancy test at screening and immediately before administration of PHI-101 and agree to use an effective contraceptive method(s) (Section 10.3.2.7.2) required in this protocol for 6 months (24 weeks) from the last dose of PHI-101

3. Indication

   ① Histologically or cytologically confirmed ovarian cancer, fallopian tube carcinoma, or primary peritoneal cancer

   ② Epithelial malignant tumors diagnosed through local histopathological findings [WHO Histological Classification, 2014]

   : except LGSC, mucinous carcinoma of the ovary, MMMT, and LAP, which are classified as LCOH, [NCCN Guideline version 2.2019].

   LAP = low malignant potential (ovarian borderline epithelial tumor); LCOH = less common ovarian histopathology; LGSC = low-grade serous carcinoma; MMMT = malignant mixed Mullerian tumor (carcinosarcoma); NCCN Guideline = National Comprehensive Cancer Network Guideline; WHO Histological Classification = World Health Organization Histological Classification ③ Platinum-refractory cancer* or platinum-resistance cancer†

   • Disease progression during platinum-based antineoplastic therapy, † Disease progression within 6 months (24 weeks) from completion of platinum-based antineoplastic therapy ④ Inoperable subjects who are refractory to, cannot receive, or refuse standard of care, which is currently known to be clinically beneficial ⑤ Subjects with ≥ 1 measurable lesion or nonmeasurable, but evaluable lesion that meets [RECIST version 1.1] RECIST = Response Evaluation Criteria in Solid Tumors
4. Expected life expectancy ≥ 12 weeks
5. [ECOG PS] ≤ 1 ECOG PS = Eastern Cooperative Oncology Group Performance Status
6. Subjects who have adequate hepatic, renal, and hematological function confirmed by the following laboratory tests (a re-test will be allowed during the screening period) ANC ≥ 1,500/mm3 (without administration of G-CSF within 2 weeks prior to baseline) Hb ≥ 10.0 g/dL (without transfusion within 2 weeks prior to baseline) Platelet count ≥ 75,000/mm3 (without transfusion within 2 weeks prior to baseline) Total bilirubin ≤ 1.5 x ULN AST and ALT ≤ 3.0 x ULN* (≤ 5 x ULN for patients with liver metastases or hepatocellular carcinoma) Serum creatinine (or CrCl) Serum creatinine ≤ 1.5 x ULN CrCl ≥ 60 mL/min (by Cockcroft-Gault equation)

7. Prior antineoplastic therapy and treatment ① Prior cytotoxic chemotherapy ≤ 5 times

   ② Reversible side effects from prior antineoplastic therapy (operation, drug, radiation therapy, etc.)* resolved to [CTCAE version 5.0] grade 1 or better

   * Subjects should not have had major surgery, antineoplastic therapy or experimental therapy, or direct radiation therapy on hematopoietic site within 4 weeks prior to baseline and should not be administered nitrosoureas or mitomycin-C within 6 weeks prior to baseline.

   CTCAE = Common Terminology Criteria for Adverse Events

8. Subjects who voluntarily decided to participate and provided written consent after they were given sufficient explanation of this study
9. Subjects who are able to understand the study procedures and restrictions and willing to comply with them during the study

Exclusion Criteria:

• 1) Subjects with known or suspected hypersensitivity or intolerance to the active ingredient or excipients of PHI-101 2) Subjects considered ineligible or unable to participate in this study according to the investigator's judgement for other reasons

Medical history or current medical condition and disease 3) Subjects with the following cardiac insufficiency or cardiovascular disease (but not limited to):

• Evidence of myocardial ischemia or myocardial infarction within 12 weeks prior to baseline

  • [NYHA Functional Classification] ≥ II NYHA = New York Heart Association ③ LVEF < 50% confirmed by ECHO or MUGA scan LVEF = left ventricular ejection fraction; ECHO = echocardiography; MUGA = Multi-gated acquisition blood pool scintigraphy

    • Clinically significant cardiac arrhythmia that is uncontrolled by the adequate and optimal treatments

      ⑤ Corrected QT (QTc)* interval > 450 msec (for both men and women) or long QT syndrome (or family history)

      * QT interval (QTcF) corrected using Fridericia's formula will be used. In case of bundle branch block, the Bazett's formula will be used (QTcB).

      4) Subjects with the following gastrointestinal diseases that affect intake or absorption of the drug (but not limited to):

• Dysphagia

  • Paralysis of intestine and intestinal obstruction

    ③ Gastrointestinal surgery that has a clinically significant effect on absorption of the drug: gastrotomy, small intestinal fistula, extensive small bowel resection, etc. (except for simple anastomosis)

    ④ Autoimmune or inflammatory disease that involves the entire gastrointestinal system or small intestines: coeliac disease, intestinal graft versus host disease, Behcet's syndrome, scleroderma involving the gastrointestinal tract, Crohn's disease, ulcerative colitis, etc.

    5) Lung diseases (but not limited to):

• New or progressive dyspnea, cough, and fever

  ② Planned diagnosis of interstitial lung disease, or interstitial pneumonia

  ③ Pulmonary fibrosis 6) Hematologic malignancy including lymphoma 7) Metastasis:

• Central nervous system metastasis or brain metastasis ② Bone metastasis 8) Infectious disease (but not limited to):

• Severe infectious disease requiring administration of antibiotics, antivirals, etc. that may affect the safety and efficacy assessments during the study

  • Active (overt) infectious disease that is uncontrolled by the adequate and optimal treatments as determined by the investigator 9) Known positive human immunodeficiency virus (HIV) 10) Active hepatitis B* or active hepatitis C†

    • HBsAg positive with HBV DNA detected † Anti-HCV positive with HCV RNA detected (qualitatively) 11) Unintentional weight loss > 10% within 12 weeks prior to informed consent 12) History of alcohol or other drug abuse within 1 year (52 weeks) prior to informed consent

Subjects who received, are receiving, or cannot stop the following therapy (medication/non-medication) 13) Subjects who need antineoplastic therapy* other than the IP during the study participation (Point radiation to alleviate bronchial obstruction, skin lesion, etc. is allowed).

* Surgery, radio(chemo)therapy, cytotoxic chemotherapy, targeted therapy (small molecule drug, monoclonal antibody), immuno-oncology drug (biological drug), hormone therapy, etc.

14) Subjects who received (used) other investigational study product or device within 2 weeks or 5 half-lives prior to informed consent (whichever is shorter) 15) Subjects on drugs (nonprescription drug, herb, homeopathy, etc.) that have a significant effect on the assessment of kinetics (metabolism, excretion, etc. in the body) or efficacy and safety of the IP within 2 weeks prior to informed consent as determined by the investigator