Solid Tumor
Conditions
Brief summary
This is a single-center, open-label, dose-escalation Phase I clinical trial to evaluate the safety and the tolerability of HLX10-HLX04 combination therapy in patients with advanced solid tumors after failure of standard of care.
Interventions
DRUGHLX04
Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection
DRUGHLX10
Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years, male or female 2. Patient with histologically or cytologically confirmed advanced malignant solid tumors who have failed standard of care, or has no standard-of-care therapy or are not suitable for standard of care at the present stage; 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1； 4. Life expectancy greater than 3 months; 5. Patient must have at least one measurable tumor lesion as defined by RECIST v1.1; the lesion concerned must not be a bone metastasis if only one target lesion is present; 6. Has adequate organ functions; 7. If the subject is a patient with hepatocellular carcinoma, Child-Pugh classification must be A. 8. A qualified patient (male or female) of childbearing potential must agree to use reliable contraceptive methods (hormonal, or barrier method or abstinence) for the course of the study and through at least 6 months after the last dose; a female patient of childbearing potential must have negative blood pregnancy test within 7 days prior to enrollment; 9. The subject must give his/her informed consent to this study prior to the trial, and voluntarily sign a written informed consent form.
Exclusion criteria
1. Histopathological confirmed head and neck cancer or squamous-cell lung cancer, or bleeding tendency in the tumor lesion judged by the investigator; 2. Has received antitumor therapy like radiotherapy, chemotherapy, targeted therapy, endocrinal therapy or immunotherapy, or other clinical study drug therapy within 4 months prior to the initial drug administration; 3. Has received a surgical operation on major viscera or experienced apparent trauma within 4 weeks from the initial drug administration, or experienced subcutaneous venous access device implantation within 7 days; 4. The adverse reactions which occurred in the previous antitumor treatment were not recovered to ≤ grade 1 based on CTCAE 4.03 assessment (except for hair loss); 5. Evidences of metastatic lesion in the patient's central nervous system; 6. Previously experienced ≥ grade 3 immune-related adverse event during immunotherapy; 7. Active, or history of autoimmune disease which may relapse (for example, systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.); 8. Currently having or have had interstitial lung disease; 9. Uncontrollable active infection(s); 10. History of immunodeficiency, including HIV antibody positive; 11. Known active hepatitis B; or hepatitis C virus infections; 12. Has bleeding tendency; 13. History of severe cardiovascular diseases; 14. Known gastrointestinal diseases as follows: Gastrointestinal perforation, abdominal fistula or abdominal abscess within 6 months before signing the informed consent; History of poorly controlled or recurrent inflammatory bowel disease; Active peptic ulcers, or \> moderate esophageal varices; 15. Known hypersensitivity to Bevacizumab, or other anti-PD-1, anti-PD-L1 monoclonal antibody agents; 16. Pregnant or breastfeeding female.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of HLX04 plus HLX10 in patients with advanced solid tumors | 28 days | The MTD is the dose with toxicity rate (estimated by isotonic regression) most approximate to the target one (30%). |
| Dose Limiting Toxicity (DLT) of HLX04 plus HLX10 in patients with advanced solid tumors | 28 days | DLT is defined as the occurrence of the following adverse events (unless judged by the investigator to be definitely unrelated to HLX04 or HLX10) within Cycle 1 (i.e., from Cycle 1 Day 1 to Cycle 1 Day 28) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) of HLX04 plus HLX10 in patients with advanced solid tumors | Day 1 of treatment up to 2 years | DCR determined by RECIST criteria |
| Duration of Response (DOR) of HLX04 plus HLX10 in patients with advanced solid tumors | Day 1 of treatment up to 2 years | DOR determined by RECIST criteria |
| PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors | Day 1 of treatment up to 2 years | Peak Plasma Concentration (Cmax) for single dose and multiple doses |
| Overall Survival (OS) of HLX04 plus HLX10 in patients with advanced solid tumors | Day 1 of treatment up to 2 years | OS determined by RECIST criteria |
| Immunogenicity | Day 1 of treatment up to 2 years | Anti-drug Antibody (ADA) Testing |
| Progression-Free Survival (PFS) of HLX04 plus HLX10 in patients with advanced solid tumors | Day 1 of treatment up to 2 years | PFS determined by RECIST criteria |
| Objective Response Rate (ORR) of HLX04 plus HLX10 in patients with advanced solid tumors | Day 1 of treatment up to 2 years | ORR determined by RECIST criteria |
Countries
China
Contacts
Primary ContactJoanne Wang
Outcome results
None listed