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

Trial summary:

This is a multi-center, open-label, phase Ib/II study of APG-2449 combined with Doxorubicin Hydrochloride Liposome to evaluate the safety and efficacy in patients with ovarian cancer.

Receptor status / problem studied:

Inclusion criteria

1. ≥ 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 relapse during platinum-based regimen therapy (at least 4 cycles) or within 6 months (184 calendar days) of the last platinum therapy. Note: Progression or recurrence of disease requires evidence of radiographic or clinical progression (e.g. cytological reports of new ascites or pleural effusion). 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 platinumcontaining therapy.
4. Up to 5 lines of prior systemic therapies are permitted; up to 2 lines of prior systemic therapy are permitted following diagnosis of platinum-resistant relapse. Note: Hormone therapy (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 Oncology Group (ECOG) score 0 to 1.
7. Life expectancy at least 3 months.
8. Adequate bone marrow, liver, kidney, and coagulation function reserve as confirmed by laboratory tests within 3 days prior to the first dose.
a) Hemoglobin (Hb)≥90 g/L independent of transfusion red blood cell transfusion and erythropoietin (EPO) use.
b) Platelet count ≥100 x 109/L and independent of platelet transfusion.
c) Absolute neutrophil count (ANC)≥109/L and independent of the use of colony-stimulating factor (CSF).
d) Total bilirubin≤1.5×upper limit of normal (ULN).
e) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (≤5× ULN for subjects with confirmed liver metastases).
f) Albumin ≥ 30 g/L.
g) Serum creatinine ≤1.5×ULN, and if serum creatinine > 1.5×ULN, creatinine clearance≥50 mL/min calculated using the Cockcroft-Gault formula.
h) Negative or weakly positive urine protein (±); or urine protein 1 + but 24-hour urine protein quantification < 1.0g/24 h.
i) International normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.5×ULN. Subjects on stable anticoagulant therapy may be enrolled at the discretion of the investigator.
9. AEs caused by previous treatment must be recovered to ≤ Grade 1 (CTCAEv5.0) or stable state as assessed by the investigator. Note: Mild toxicities without safety concerns, such as alopecia 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) in Appendix 3. 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 consent 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 imaging.

Exclusion criteria

Patients who meet any of the following exclusion criteria are not to be enrolled in this study:
1. Major surgery or major trauma within 28 days prior to the first dose or diagnostic biopsy within 14 days prior to the first dose. Note: Patients who are expected to require major surgery during study treatment will also be excluded. Subjects who had a diagnostic biopsy within 14 days prior to the first dose could also be enrolled if the investigator judged that the diagnostic biopsy did not affect the efficacy assessments during the study.
2. Have received systemic antineoplastic agents including investigational agents within a specified period, including targeted therapy within 14 days or 5 half-lives (whichever is shorter) before the first dose, or immunotherapy within 28 days before the first dose.
3. Radiotherapy within 14 days prior to first dose.
4. Previous FAK inhibitors
5. Previous cumulative anthracycline dose ≥ 550 mg/m2.
6. Other sites or other histological types of tumors other than existing ovarian cancer within 3
years before the first dose, except curable tumors such as cervical carcinoma in situ.
7. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects may be considered for enrollment if they have previously treated brain metastases that are clinically stable or radiologically stable within 14 days prior to the first dose (confirmed by repeat imaging at least 4 weeks apart and performed at screening).
8. Major cardiovascular or cerebrovascular disease (such as congestive heart failure, acute myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, deep venous thrombosis) within 6 months before the first dose, or any of the following abnormalities:
a) QTc interval > 480 milliseconds.
b) Left ventricular ejection fraction (LVEF) < 50%.
c) New York Heart Association (NYHA) cardiac function classification (Appendix 4) ≥ grade 2.
d) Severe arrhythmia.
e) Poorly controlled hypertension or diabetes.
f) Other serious heart disease.

9. Clinical symptoms of pleural effusion, pericardial effusion, or ascites should need puncture, drainage or drainage within 1 month before the first dose, except for a small amount of effusion on imaging but not accompanied by clinical symptoms.
10. Presence of malabsorption syndrome, or inability to take oral medication, or bowel obstruction.
11. Presence of serious gastrointestinal disease such as poorly controlled gastrointestinal inflammatory disease (active Crohn ‘s disease or ulcerative colitis) or poorly controlled gastrointestinal bleeding. Presence of clinical or radiographic evidence of ileus, or etiology of previous recurrent ileus will not be excluded.
12. Uncontrolled or active infectious diseases such as HIV, hepatitis B and hepatitis C; or active COVID-19 infection. (Patients who have received COVID-19 vaccination will be considered as eligible for the study).
13. Systemic administration of moderate or strong inhibitors/inducers of CYP3A4, CYP2C9 or CYP2C19 within 7 days prior to the first dose. Systemic administration of CYP3A4 sensitive substrates with narrow therapeutic index within 7 days prior to the first dose.
14. Other factors may cause the subject to be forced to terminate the study halfway as judged by the investigator, such as having other serious diseases (including mental illness) requiring concomitant treatment, severely abnormal laboratory tests, family, or social factors, which may affect the safety of the subject or the collection of trial data, etc.

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Open for recruitment

Trial Title



Ovarian cancer

Type of trial


Type of treatement

Medical Oncology





Principal Investigator
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