Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of HLX26 and HLX10 in Patients With Advanced/Metastatic Solid Tumor

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of HLX26 Monoclonal Antibody Injection in Combination With HLX10 Monoclonal Antibody Injection in Patients With Advanced/Metastatic Solid Tumor

This study is a open-label, phase I, dose escalation clinical study to evaluate the safety and tolerability of HLX26 and HLX10 in the treatment of patients with advanced/metastatic solid tumors.

Study Overview

• Status: Completed
• Conditions: Adult Solid Tumor
• Intervention / Treatment: Drug: HLX26; Drug: HLX10

Detailed Description

This study is a open-label, phase I, dose escalation clinical study to evaluate the safety and tolerability of HLX26 and HLX10 in the treatment of patients with advanced/metastatic solid tumors. In this study, a 3 + 3 dose escalation design was used. The patients will be given different doses(500mg, 800mg Q3W) of HLX26 Plus fixed dose of HLX10(300mg) intravenously. Observation period of DLT lasts for 3 weeks after the first administration of HLX26.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yumei Yang; Phone Number: 021-33395800*6541; Email: yumei_yang@henlius.com
• Study Contact Backup: Name: Ni Zhang; Email: ni_zhang@henlius.com

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China
      • Xuzhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have a full understanding of the study content, process, and possible adverse reactions before the study, and sign the informed consent form (ICF); voluntarily participate in the study; be able to complete the study as per protocol requirements;
2. Aged ≥ 18 years and ≤75 years at the time of signing the ICF;
3. Patients with histologically or cytologically confirmed advanced malignant solid tumor who have failed or cannot receive the standard treatment;
4. With at least one measurable lesion according to RECIST V1.1 (for solid tumors);
5. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at enrollment;
6. Expected survival > 3 months;
7. Patients with Non-Small Cell Lung Cancer had no EGFR sensitivity mutation or gene rearrangement or jump of ALK, ROS1, RET and METex14;
8. For patients with hepatocellular carcinoma, Child-Pugh score has to be A;
9. Have appropriate hematological functions: no blood transfusion or Treatment for hemocytopenia within 14 days before the first administration; absolute neutrophil count ≥ 1500/μL; haemoglobin ≥ 9 g/dL; platelet count ≥ 90,000/μL;
10. Have appropriate coagulation functions: activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; prothrombin time (PT) ≤ 1.5 × ULN; international normalized ratio (INR) ≤ 1.5 × ULN;
11. Have appropriate liver functions: total bilirubin level ≤ 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN (AST and ALT ≤ 5 × ULN for patients with known liver metastasis or primary hepatocellular carcinoma);
12. Have appropriate renal functions: blood creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (calculated by Cockcroft-Gault formula);
13. The first administration of the investigational product must be: at least 28 days apart from the previous major surgery, medical device treatment, or local radiotherapy; at least 28 days apart from the previous cytotoxic chemotherapy, immunotherapy, and biological agent therapy; at least 14 days apart from the previous hormone therapy and surgical operation; at least 21 days or 5 half-lives apart from the administration of small molecule targeted drugs, whichever is longer; at least 14 days apart from the traditional Chinese medicine for tumor indications; at least 14 days apart from the endocrine therapy; For any drug with antitumor effect not listed above, at least 5 half lives shall be separated before administration of the first study drug;
14. Male and female subjects with child-bearing potential must agree to use at least one highly effective contraception method during the study and within at least 6 months after the last administration of the investigational product.

Exclusion Criteria:

1. The adverse reactions (except alopecia and other adverse reactions determined by the investigator to have no safety risk) of previous anti-tumor therapy have not yet recovered to ≤ grade 1 (CTCAE V5.0);
2. Those who are known to have severe anaphylaxis (grade 4 or greater in CTCAE V5.0) to macromolecular protein preparations/monoclonal antibodies or to any component of the investigational product;
3. Patients with any of the following unstable or poorly controlled diseases:1)Active systemic infectious diseases requiring intravenous antibiotics within 2 weeks before the first administration of the investigational product;2)Any poorly-controlled cardiovascular and cerebrovascular clinical symptoms or diseases, including but not limited to: (1) NYHA Class II or greater cardiac failure or left ventricular ejection fraction (LVEF) < 50%; (2) unstable angina pectoris; (3) myocardial infarction and cerebral infarction within 6 months, (4) clinically significant supraventricular or ventricular arrhythmia without clinical intervention or poorly controlled after clinical intervention;3)Other chronic diseases which, in the opinion of the investigator, may compromise the safety of the patient or the integrity of the study;
4. Assessed as unsuitable for inclusion by the investigator, due to brain metastases, spinal cord compression, or cancerous meningitis with clinical symptoms, or uncontrolled brain or spinal cord metastases that have been evidenced;
5. Previous grade 3 or greater irAEs in immunotherapy;
6. Have had other malignant tumors within 5 years before enrollment, except: (a) those with cured cervical carcinoma in situ or non-melanoma skin cancer; (b) those with cured second primary cancer without recurrence within 5 years; (c) those with double primary cancers believed to be able to benefit from this study; (d) those whose metastasis has been clearly excluded from a certain primary tumor source;
7. those who have received anti-LAG-3 antibody therapy;
8. Have active autoimmune diseases (including but not limited to the following diseases or syndromes, such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, and hypothyroidism), except: vitiligo or cured childhood asthma/allergy that does not need any intervention in adulthood, autoimmune mediated hypothyroidism treated with stable dose of thyroid replacement hormone, and type I diabetes treated with stable dose of insulin; those in a stable condition and requiring no systemic immunosuppressant therapy (including corticosteroid hormone) are allowed to be enrolled;
9. Have received systemic corticosteroids (prednisone > 10 mg/d or equivalent dose of similar drug) or other immunosuppressants within 14 days before the first administration; Except: patients treated with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; those with short term use of corticosteroids for prophylaxis, such as contrast agents;
10. Patients in pregnancy [confirmed by serum beta-human chorionic gonadotropin (ß-HCG) test] or breastfeeding;
11. With a history of immunodeficiency, including human immunodeficiency virus (HIV)-positive or other acquired or congenital immunodeficiencies, or a history of organ transplantation;
12. Patients with active HBV or HCV infection (HBV DNA ≥ 10*4 copies/mL or positive HCV RNA, but patients with HBV DNA < 10*4 copies / mL after treatment will be excluded); Subjects with co-infection of hepatitis B and hepatitis C (HBsAg or HBcAb positive, and HCV antibody positive);
13. Have received live vaccines within 28 days prior to the first administration;
14. Interstitial pneumonia occurred during previous anti-tumor treatment;
15. Patients whose medical history or any other evidence suggests that participation in the study may confuse the results, or subjects for whom the investigator believes the study is not in their best interest;
16. Participating in other clinical studies or less than 14 days from the end of the treatment of the previous clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Cohort 1; In this cohort, the dose of HLX26 is 500mg. HLX26 will be intravenously administered every 3 weeks. HLX10 will be intravenously administered every 3 weeks with the fixed dose of 300mg. Patients will receive the treatment until they have been in therapy for 2 years, develop progressive disease (PD) without any clinical benefit, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).	Drug: HLX26; Humanized Anti-Lymphocyte Activation Gene-3 Monoclonal Antibody; Other Names: Anti-LAG-3 Monoclonal Antibody; Drug: HLX10; Humanized Anti-Programmed Death-1 Monoclonal Antibody; Other Names: Anti-PD-1 Humanized Monoclonal Antibody; SERPLULIMAB
Experimental: Dose Cohort 2; In this cohort, the dose of HLX26 is 800mg. HLX26 will be intravenously administered every 3 weeks. HLX10 will be intravenously administered every 3 weeks with the fixed dose of 300mg. Patients will receive the treatment until they have been in therapy for 2 years, develop progressive disease (PD) without any clinical benefit, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).	Drug: HLX26; Humanized Anti-Lymphocyte Activation Gene-3 Monoclonal Antibody; Other Names: Anti-LAG-3 Monoclonal Antibody; Drug: HLX10; Humanized Anti-Programmed Death-1 Monoclonal Antibody; Other Names: Anti-PD-1 Humanized Monoclonal Antibody; SERPLULIMAB
Experimental: Dose Cohort 3; In this cohort, the dose of HLX26 is 1600mg. HLX26 will be intravenously administered every 3 weeks. HLX10 will be intravenously administered every 3 weeks with the fixed dose of 300mg. Patients will receive the treatment until they have been in therapy for 2 years, develop progressive disease (PD) without any clinical benefit, death, intolerable toxicity, or withdraw the informed consent (whichever occurs first).	Drug: HLX26; Humanized Anti-Lymphocyte Activation Gene-3 Monoclonal Antibody; Other Names: Anti-LAG-3 Monoclonal Antibody; Drug: HLX10; Humanized Anti-Programmed Death-1 Monoclonal Antibody; Other Names: Anti-PD-1 Humanized Monoclonal Antibody; SERPLULIMAB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT	The Dose-Limiting Toxicity (DLT) of HLX26 in combination with HLX10 within 3 weeks after the first Administration in patients with Advanced/Metastatic Solid Tumors	from day1 to day 21
MTD	The Maximum Tolerated Dose (MTD) of HLX26 in combination with HLX10 within 3 weeks after the first Administration in patients with Advanced/Metastatic Solid	from day1 to day 21

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2022
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): January 31, 2024

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 28, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 4, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: LAG-3
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antineoplastic Agents, Immunological
• Other Study ID Numbers: HLX26-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No