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

Phase 1

Completed

• Conditions: Adult Solid Tumor
• Interventions: Drug: HLX26; Drug: HLX10

• Registration Number: NCT05400265
• Lead Sponsor: Shanghai Henlius Biotech

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-05-23
• Study First Submitted QC: 2022-05-28
• Study First Posted: 2022-06-01
• Study Start: 2022-07-26
• Primary Completion: 2023-08-31
• Study Completion: 2024-01-31
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-04
• Last Update Posted: 2024-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 9

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Cohort 1	HLX26	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).
Dose Cohort 1	HLX10	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).
Dose Cohort 2	HLX26	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).
Dose Cohort 3	HLX26	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).
Dose Cohort 3	HLX10	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).
Dose Cohort 2	HLX10	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).

Primary Outcome Measures

Name	Time	Method
DLT	from day1 to day 21	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
MTD	from day1 to day 21	The Maximum Tolerated Dose (MTD) of HLX26 in combination with HLX10 within 3 weeks after the first Administration in patients with Advanced/Metastatic Solid

Trial Locations

Locations (1)

Xuzhou Central Hospital; 🇨🇳 Xuzhou, Jiangsu, China