IN10018 in Combination With Pegylated Liposomal Doxorubicin (PLD) vs. Placebo in Combination With PLD for the Treatment of Platinum-resistant Recurrent Ovarian Cancer

Inclusion Criteria:

1. Ability to understand and willingness to sign informed consent(s). Signed informedconsent must be obtained before any study specific procedures, except thoseprocedures used as institutional standard of care falling into the protocolspecified window and fulfilling study specific requirements such as tumor imaging.

2. Female subjects ≥ 18 years at the time of signing informed consent.

3. Histologically confirmed epithelial ovarian cancer, fallopian tube cancer or primaryperitoneum cancer and its subtype is high-grade serous carcinoma (HGSC).

4. Have received platinum containing therapy and have radiological relapse orprogression during platinum containing treatment or < 6 months (184 calendar days)after completion of prior platinum-based therapy (at least 4 cycles). Note: Disease progression or recurrence requires evidence of radiographic orclinical progression (e.g., new ascites or cytological reports of pleural fluid),and elevated CA125 alone is not a criterion for progression or recurrence. Primaryplatinum-refractory ovarian cancers (defined as progression during or within 4 weeksafter first line platinum-based therapy) is excluded, while secondaryplatinum-refractory disease is allowed and does not require at least 4 cycles ofplatinum-based therapy.

5. Maximum total of 3 prior lines of systemic therapy are allowed. Note: Hormonaltherapies (e.g., tamoxifen), PARP inhibitors and bevacizumab given in themaintenance setting post response to platinum-based therapy will not count as atreatment line. Other maintenance regimens may also not count as a treatment line bydiscussion between the investigator and sponsor.

6. At least one measurable lesion can be accurately measured per RECIST 1.1 as assessedby investigator. Note: Lesions situated in a previously irradiated area are considered measurable ifprogression has been demonstrated in such lesions.

7. ECOG performance status of 0 or 1.

8. Life expectancy of at least 3 months as assessed by investigator.

9. Availability of archival or fresh (newly obtained) tumor tissue sample duringscreening phase: fresh tumor tissue sample obtained after most recent relapse orprogression is preferred; if no sample or not sufficient number of slides (refer toLaboratory Manual which will be provided separately) can be provided or collected, ajoint decision between sponsor and investigator is needed for the enrollment of thissubject.

10. Must have recovered from all AEs due to previous therapies to ≤ Grade 1 (CTCAE 5.0)or stable status as assessed by investigator. Note: subjects with minor toxicities with no safety concern like alopecia and Grade 2 neuropathy could be enrolled per evaluation of investigator.

11. Adequate bone marrow, liver, renal, and coagulation function within 7 days prior torandomization.

12. Hemoglobin (Hb) ≥ 100 g/L (10 g/dL), independent of blood infusion, red bloodcell transfusion and erythropoietin (EPO) use within 14 days prior to thescreening period examination.

13. Platelet count ≥ 100 × 109/L, independent of platelet infusion within 14 daysprior to the screening period examination.

14. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, independent of colonystimulating factor (CSF) use within 14 days prior to the screening periodexamination.

15. Total bilirubin ≤ upper limit of normal (ULN).

16. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for subjects with documented liver involvement of their disease).

17. Serum creatinine ≤ 1.5 × ULN, Estimated Creatinine clearance rate (Clcr) by theCockcroft-Gault (C-G) equation ≥ 60 mL/min or estimated glomerular filtrationrate (eGFR) from the Modification of Diet in Renal Disease (MDRD) equation ≥ 60mL/min.

18. Urinary protein negative or trace (±); or urinary protein ≥ 1+ but with a urineprotein to creatinine ratio (UPCR) in a morning spot urine sample < 0.5 or a 24-hour urine protein < 0.5 g/24 h.

19. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastintime (aPTT) ≤ 1.5 × ULN. Subjects with stable anticoagulation treatment isallowed.

20. A female subject is eligible to participate if she is not pregnant, notbreastfeeding, and at least one of the following conditions applies:

21. Not a woman of childbearing potential (WOCBP) as defined in section 10.4Appendix 4 of the full protocol.OR

22. A WOCBP who agrees to follow the contraceptive guidance in section 10.4Appendix 4 of the full protocol during the treatment period and through 3months after the last dose of study treatment.

Exclusion Criteria:

1. Has had major surgery or significant traumatic injury within 28 days prior torandomization, or diagnostic biopsies within 14 days prior to randomization. Note: Subjects with anticipation of the need for major surgery during studytreatment should be excluded. Subjects who underwent diagnostic biopsy within 14days prior to randomization may also be enrolled if the investigator and sponsordetermine that the diagnostic biopsy will not affect the efficacy evaluation.

2. Has received prior systemic anticancer therapy including investigational agents,such as within 14 days or less than 5 half-lives (whichever is shorter) ofchemotherapy or targeted therapy, or within 28 days of immunotherapy, macromoleculardrugs (eg., bevacizumab) or investigational drugs prior to randomization.

3. Has received prior radiotherapy within 14 days prior to randomization. Note: A 7-daywashout is permitted for palliative radiation (≤ 14 days of radiotherapy) tonon-central nervous system (CNS) disease.

4. Has received prior treatment of any FAK inhibitor or prior treatment of PLD.

5. Has a known previous or concurrent cancer that is distinct in primary site orhistology from current ovarian cancer within 3 years prior to randomization, exceptfor curatively treated cancers such as cervical/breast/prostate carcinoma in situand basal cell carcinoma.

6. Has known active central nervous system (CNS) metastases and/or carcinomatousmeningitis. Note: Subjects with previously treated brain metastases may participate providedthey are radiologically stable (i.e., without evidence of progression) for at least 4 weeks apart by repeat imaging (note that the repeat imaging should be performedduring screening phase) for at least 28 days prior to randomization.

7. Has a history of major cardiovascular, cerebrovascular or thromboembolic diseases (e.g., congestive heart failure, acute myocardial infarction, unstable angina,stroke, transient ischemic attack, deep vein thrombosis or pulmonary embolism)within 6 months before randomization, or has any of the following abnormality:

8. QTc interval corrected using Fridericia's formula > 470 ms (based on QTcF).

9. Left ventricular ejection fraction (LVEF) < 50%.

10. New York Heart Association (NYHA) functional classification ≥ Grade 2.

11. Clinically significant arrhythmia.

12. Uncontrolled hypertension or diabetes.

13. Other clinically significant heart diseases.

14. Has known pleural effusion, pericardial effusion or ascites accompanied by clinicalsymptoms or requiring puncture or drainage. Subjects who received drainage withinthe first 3 months of randomization should be excluded. A small amount of ascitesthat can only be detected by imaging examination and without clinical symptom isallowed.

15. Has malabsorption syndrome or inability to take oral drugs.

16. Has clinically significant gastrointestinal abnormalities including uncontrolledgastrointestinal inflammatory lesions (Crohn's disease, or ulcerative colitis inactive) or uncontrolled gastrointestinal bleeding.

17. Clinical or radiographic evidence of intestinal obstruction, or aetiology ofprevious recurrent ileus not excluded.

18. Currently have interstitial pneumonia (except for radiation pulmonary fibrosis thatdoes not require hormonal therapy).

19. Has not well controlled active infection after systemic therapy.

20. Has known human immunodeficiency virus (HIV) infection or known active Hepatitis Bor Hepatitis C virus infection. Note: No HIV, Hepatitis B and Hepatitis C testing is required unless mandated bylocal health authority and/or site.

21. Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the study, interfere with thesubject's participation for the full duration of the study, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator.

22. Has a known psychiatric or substance abuse disorder that would interfere with thesubject's ability to cooperate with the requirements of the study.

23. Known allergy or hypersensitivity to IN10018 or PLD, or their ingredients.

24. Has received prior cumulative anthracycline dose of 550 mg/m2 or more.

25. Has received systemic treatment of CYP3A4, CYP2D6 or P-gp strong inhibitors/inducerswithin 14 days prior to randomization, or anticipation of the systemic treatment ofthese drugs during Treatment Phase.