Recombinant Humanized Anti-CD47 / PD-1 Bifunctional Antibody HX009 Injection in the Treatment of Advanced Solid Tumors

• Status: Recruiting
• Trial end date: 2023-02-10
• Target enrollment: 0
• Participant gender: All

Summary

This is a multi-center phase II clinical trial to evaluate the anti-tumor activity and safety of HX009 in subjects with advanced solid tumors.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Waterstone Hanxbio Pty Ltd

Criteria

Inclusion Criteria:

1. Male or female, aged 18 to 75 years, inclusive;

2. Eastern Cooperative Oncology Group performance status of 0 to 1;

3. Having unresectable locally advanced or metastatic solid tumor (confirmed by histology or pathology);

4. Participants must have failed the standard treatment (due to either disease progression or intolerable toxicity) or the standard of care had not been established for the specific condition;

5. Measurable extracranial lesion based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1;

6. Life expectancy ≥12 weeks;

7. For prior anti-tumor therapies, the following conditions must be met:

• The interval between local radiotherapy or radiotherapy for bone metastasis and the first dose of is ≥2 weeks;

• The interval between the last dose of previous chemotherapy, immunotherapy (including PD-1, PD-L1 or CTLA-4 antibodies), biological therapy (tumor vaccines, cytokines, or anti-cancer growth factors) and the first dose of HX009 is ≥4 weeks (The interval between the last dose of small molecule targeted drugs and the first dose of HX009 is ≥2 weeks);

• The interval between the last dose of anti-cancer Traditional Chinese Medicine and the first dose of HX009 is ≥ 2 weeks;

• Has had previously serious adverse reactions (pneumonia or myocarditis) related to previous PD1/PDL1 inhibitors that preclude their treatment according to the investigator's criteria;

8. Participants with asymptomatic central nervous system (CNS) metastases are eligible only if they have no evidence of progression by imaging for at least four weeks prior to the first dose of HX009 and are not using corticosteroids;

9. Appropriate organ functions according to the following laboratory tests :

• Absolute neutrophil count (ANC)≥1.5 × 10^9/L

• Absolute white blood cell count (WBC) ≥3.0×10^9/L

• Platelet count ≥90 × 10^9/L

• Hemoglobin ≥90 g/L (no blood transfusion within 4 weeks prior to HX009 administration)

• Serum creatinine≤1.5 upper limit of normal (ULN)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN , ALT and AST ≤5 × ULN for subjects with liver metastases or liver cancer

• Serum Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN)

• International normalized ratio (INR) ≤ 2 x ULN, or activated partial thromboplastin time (APTT) ≤ 1.5 x ULN (except for patients receiving anticoagulant therapy) ;

10. Reproductive males or females who are likely to become pregnant must use highly effective contraceptive methods (such as oral contraceptives, intrauterine contraceptives, sexual control or barrier contraceptives combined with spermicides) during the trial, and continue contraception for 6 months after the last dose of HX009;

11. Participants must be willing and able to provide written informed consent for the study, and have good compliance;

Exclusion Criteria:

1. Participants having a known additional malignancy within 3 years before enrollment, except for malignancies with low risk of metastasis and death (5-year survival rate> 90%), such as completely resected basal cell or squamous cell skin cancer, or cervical carcinoma in situ, or superficial bladder cancer;

2. Has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. (Subjects with > Grade 1 neuropathy or hair loss are an exception to this criterion and may qualify for the study according to the judgment of the investigator);

3. Participants with active or history of autoimmune diseases are ineligible, except for the following conditions:

• Participants with type 1 diabetes who are in stable condition after using a fixed dose of insulin;

• Autoimmune hypothyroidism requiring only hormone replacement therapy;

• Autoimmune skin diseases that do not require systemic treatment (such as eczema, skin rashes that account for less than 10% of the body surface, or psoriasis without ophthalmological symptoms);

4. Participants expected to undergo major surgery within 28 days before the planned first dose of HX009;

5. Participants receiving systemic corticosteroids equivalent to >10 mg prednisone/day or other immunosuppressive drugs within 14 days before the first administration of HX009, except for the following conditions:

• Participants using topical or inhaled corticosteroids;

• Short-term (≤7 days) use of corticosteroids to prevent or treat non-autoimmune allergic diseases;

6. Participants with known interstitial lung disease or non-infectious pneumonia requiring systemic treatment with corticosteroids;

7. Participants having clinically serious cardiovascular diseases (unstable angina or myocardial infarction within 6 months before enrollment), diabetes, or hypertension;

8. Participants having arterial or venous thrombosis or embolic events (cerebrovascular events including transient ischemic attack, deep vein thrombosis, or pulmonary embolism) within 6 months before the first administration of HX009;

9. Participants having a history of human immunodeficiency virus infection, or having other acquired or congenital immunodeficiency diseases, or having a history of organ or stem cell transplantation;

10. Participants with active chronic hepatitis B or active hepatitis C;

11. Participants having a serious infection within 4 weeks before the first administration of HX009, or having an active infection that require oral or intravenous antibiotic treatment;

12. Participants having severe allergic reactions to macromolecular protein preparations/monoclonal antibodies, or to any drug component of HX009 (CTCAE 5.0 grade greater than 3);

13. Participated in other drug clinical trials within 4 weeks before the first administration of HX009;

14. Alcohol dependent or known history of drug abuse within the past year;

15. Participants with poor compliance due to known history of neurological or mental disorders, such as epilepsy, dementia;

16. Pregnant or breastfeeding women;

17. Participants with pleural effusion, abdominal effusion or pericardial effusion with clinical symptoms;

18. Participants having received colony-stimulating factor, granulocyte macrophage colony-stimulating factor or recombinant erythropoietin within 2 weeks prior to the start of treatment;

19. Participants, in the judgement of the investigator, who are unlikely to comply with the study procedures, restrictions, and requirements of the study.