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

1. Ability to understand and willingness to sign informed consent(s). Signed informed consent must be obtained before any study specific procedures, except those procedures used as institutional standard of care falling into the protocol specified 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 primary peritoneum cancer and its subtype is high-grade serous carcinoma (HGSC).

4. Have received platinum containing therapy and have radiological relapse or progression 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 or clinical progression (e.g., new ascites or cytological reports of pleural fluid), and elevated CA125 alone is not a criterion for progression or recurrence. Primary platinum-refractory ovarian cancers (defined as progression during or within 4 weeks after first line platinum-based therapy) is excluded, while secondary platinum-refractory disease is allowed and does not require at least 4 cycles of platinum-based therapy.

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

6. At least one measurable lesion can be accurately measured per RECIST 1.1 as assessed by investigator.

Note: Lesions situated in a previously irradiated area are considered measurable if progression 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 during screening phase: fresh tumor tissue sample obtained after most recent relapse or progression is preferred; if no sample or not sufficient number of slides (refer to Laboratory Manual which will be provided separately) can be provided or collected, a joint decision between sponsor and investigator is needed for the enrollment of this subject.

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 to randomization.

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

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

3. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, independent of colony stimulating factor (CSF) use within 14 days prior to the screening period examination.

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

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

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

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

8. International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Subjects with stable anticoagulation treatment is allowed.

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

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

OR

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

What this study is about