A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Anti-PD-1 Antibody (HLX10) in Combination With Avastin Biosimilar (HLX04) in Patients With Advanced Solid Tumors

Solid Tumor Clinical Trial

Official title:

A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection (HLX10) in Combination With Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection (HLX04) in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03757936
• Other study ID #: HLX10HLX04-001
• Status: Recruiting
• Phase: Phase 1
• Start date: November 27, 2018
• Est. completion date: December 27, 2020

Study information

• Verified date: May 2019
• Source: Shanghai Henlius Biotech
• Contact: Joanne Wang
• Phone: +86-021-33395800-6024
• Email: Joanne_wang[@]henlius.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 27, 2020
• Est. primary completion date: September 27, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• HLX04
Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection
• HLX10
Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection

Locations

Country	Name	City	State
China	Shanghai East Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Henlius Biotech

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of HLX04 plus HLX10 in patients with advanced solid tumors	The MTD is the dose with toxicity rate (estimated by isotonic regression) most approximate to the target one (30%).	28 days
Primary	Dose Limiting Toxicity (DLT) of HLX04 plus HLX10 in patients with advanced solid tumors	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)	28 days
Secondary	PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors	Peak Plasma Concentration (Cmax) for single dose and multiple doses	Day 1 of treatment up to 2 years
Secondary	PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors	Area under the plasma concentration versus time curve (AUC) for single dose and multiple doses	Day 1 of treatment up to 2 years
Secondary	Objective Response Rate (ORR) of HLX04 plus HLX10 in patients with advanced solid tumors	ORR determined by RECIST criteria	Day 1 of treatment up to 2 years
Secondary	Disease Control Rate (DCR) of HLX04 plus HLX10 in patients with advanced solid tumors	DCR determined by RECIST criteria	Day 1 of treatment up to 2 years
Secondary	Duration of Response (DOR) of HLX04 plus HLX10 in patients with advanced solid tumors	DOR determined by RECIST criteria	Day 1 of treatment up to 2 years
Secondary	Progression-Free Survival (PFS) of HLX04 plus HLX10 in patients with advanced solid tumors	PFS determined by RECIST criteria	Day 1 of treatment up to 2 years
Secondary	Overall Survival (OS) of HLX04 plus HLX10 in patients with advanced solid tumors	OS determined by RECIST criteria	Day 1 of treatment up to 2 years
Secondary	Immunogenicity	Anti-drug Antibody (ADA) Testing	Day 1 of treatment up to 2 years