A Phase Ib/II Study of APG-2449 in Combination with Doxorubicin Hydrochloride Liposome in Patients with Ovarian Cancer

ACTRN 12623000174684

Brief Summary

This study aims to establish the safety and best tolerated dosethe amount of medication taken of a new investigational drug called APG-2449 in participants with ovarian cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs.

Intervention/Treatment

• Drug: APG-2449
• Drug: Doxorubicin Hydrochloride Liposome (PLD).

Inclusion Criteria

Patients must meet all the following inclusion criteria to be eligible for participation in this study:

1. Greater than or equal to 18 years of age.
2. Histologically confirmed ovarian cancer, including fallopian tube cancer, or primary peritoneal cancer, especially the subtype high-grade serous ovarian cancer (HGSOC).
3. Prior treatment with a platinum-based regimen and disease progression or relapsethe return of disease during platinum-based regimen therapy (at least 4 cycles) or within 6 months (184 calendar days) of the last platinum therapy. Note: Progression or recurrenceto occur or happen again of disease requires evidence of radiographic or clinical progression (e.g. cytological reports of new ascitesa buildup of fluid in the abdomen or pleural effusionabnormal fluid build-up in the pleural space, which can cause chest pain and breathing difficulties). Primary platinum-refractory (defined as progression during or within 4 weeks post to the first platinum-containing regimen) subjects could not be enrolled, but secondary platinum-refractory subjects could be enrolled in the study without the requirement for at least 4 cycles of platinum containing therapy.
4. Up to 5 lines of prior systemic therapies are permitted; up to 2 lines of prior systemic therapy are permitted following diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of platinum-resistant relapse. Note: Hormone therapymedication that alters the levels of certain hormones in the body, such as oestrogen and progesterone (eg, tamoxifen), maintenance therapy with PARP inhibitors and bevacizumab are not counted as treatment lines. Other special maintenance options may not be counted as treatment lines.
5. Presence of at least one measurable tumor lesion (as assessed by the investigator) according to RECIST 1.1 criteria.
6. Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group (ECOG) score 0 to 1.
7. Life expectancy at least 3 months.
8. Adequate bone marrowsoft, spongy tissue found in bones that makes blood cells, liver, kidneya pair of bean-shaped organs in the abdomen that are responsible for filtering excess water and waste products from the blood and converting them into urine to be removed from the body, and coagulation function reserve as confirmed by laboratory tests within 3 days prior to the first dose:
   • Hemoglobin (Hb) greater than or equal to 90 g/L independent of transfusion red bloodthe red bodily fluid that transports oxygen and other nutrients around the body cell transfusion and erythropoietin (EPO) use.
   • Platelet count greater than or equal to 100 x 10^9/L and independent of platelet transfusion.
   • Absolute neutrophil count (ANC) greater than or equal to 10^9/L and independent of the use of colony-stimulating factor (CSF).
   • Total bilirubin less than or equal to 1.5×upper limit of normal (ULN).
   • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5×ULN (less than or equal to 5× ULN for subjects with confirmed liver metastases).
   • Albumin greater than or equal to 30 g/L.
   • Serum creatinine less than or equal to 1.5×ULN, and if serum creatinine greater than 1.5×ULN, creatinine clearance greater than or equal to 50 mL/min calculated using the Cockcroft-Gault formula.
   • Negative or weakly positive urine protein (±); or urine protein 1 + but 24-hour urine protein quantification less than 1.0g/24 h.
   • International normalized ratio (INR) less than or equal to 1.5 and activated partial thromboplastin time (aPTT) less than or equal to 1.5×ULN. Subjects on stable anticoagulantmedication used to prevent or reduce blood clots; also known as blood thinners therapy may be enrolled at the discretion of the investigator.
9. AEs caused by previous treatment must be recovered to Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 1 (CTCAEv5.0) or stable state as assessed by the investigator. Note: Mild toxicities without safety concerns, such as alopeciathe partial or complete absence of hair from areas of the body where it normally grows; baldness and grade 2 neuralgia, may be included at the investigator ‘s discretion.
10. Female subjects must be non-pregnant and non-lactating and meet either of the following: a) Does not meet the definition of women of childbearing potential (WOCBP). Or b) WOCBP agrees to comply with the contraception guidelines during the treatment period and for 3 months following the last dose.
11. Willing to sign an informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment. form. Voluntary written informed consent must be obtained from the subject before any study-specific procedures are performed, unless the procedures are performed according to clinical criteria and fall within the protocol-required time window and meet study-specific requirements, such as tumor imagingtests that create detailed images of areas inside the body.