A Study of LVGN6051 Combination Therapy in Patient With Head and Neck Squamous Cell Carcinoma (HNSCC)

NCT ID: NCT06378177

Last Updated: 2024-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-21

Study Completion Date

2027-10-31

Brief Summary

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The purpose of this study is to assess the safety and efficacy of LVGN6051 (4-1BB agonistic antibody) combined with toripalimab (anti-PD-1 antibody) and paclitaxel (anti-tubulin chemotherapy) in patients with recurrent/metastatic head and neck squamous cell carcinoma who rapidly progress from previous neoadjuvant, curative, or adjuvant platinum-containing therapy, or who are currently contraindicated for platinum-containing treatment.

Detailed Description

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This is a multicenter, open-labeled, single-arm Phase 2 clinical study to evaluate the safety and efficacy of LVGN6051 in combination with toripalimab and paclitaxel in selected patients with recurrent/metastatic head and neck squamous cell carcinoma under the guidance of Good Clinical Practise(GCP).

This study comprises two parts. Part 1 (Safety run-in Phase) is designed to confirm the dose of combination therapy in Part 2. Part 1 includes a "3+3 dose-escalation design" for 2 dose levels, i.e., LVGN6051 1 mg/kg or LVGN6051 2 mg/kg with standard doses of toripalimab and paclitaxel (every 3 weeks for a treatment cycle). Part 1 will treat up to 12 DLT-evaluable patients, and the Data monitoring committee(DMC), based on the safety profile, will confirm the recommended dose for combination therapy in Part 2.

Part 2 (Efficacy Exploration Phase) will treat up to 52 patients with evaluable tumor response (efficacy) using the recommended dose of combination therapy determined in Part 1. The sample size for Part 2 is based on Simon's two-stage minimax design, which uses the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) objective response rate (ORR) as the primary efficacy endpoint. The first stage will include 28 patients with evaluable tumor response (efficacy). If 6 or more responses are observed, the second stage 2 will consist of an additional 24 patients with evaluable tumor response. Part 1 patients with the same dose level as Part 2, if they meet evaluable tumor response, can be included in the required 52 patients with evaluable tumor response.

Conditions

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Head and Neck Squamous Cell Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

This is a multicenter, open-labeled, single-arm Phase 2 clinical study.This study comprises two parts. Part 1 (Safety Run-in Phase) is designed to confirm the dose of combination therapy in Part 2.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LVGN6051combined with toripalimab and paclitaxel

LVGN6051 in combination with toripalimab and paclitaxel

Group Type EXPERIMENTAL

LVGN6051 Monoclonal Antibody Injection

Intervention Type BIOLOGICAL

LVGN6051 Monoclonal Antibody Injection:1 mg/kg or 2 mg/kg, every 3 weeks(Q3W) , on the first day of the treatment cycle for up to 2 years.

toripalimab Injection

Intervention Type BIOLOGICAL

toripalimab Injection: 240mg fixed dose,Q3W, on the first day of the treatment cycle for up to 2 years.

Paclitaxel injection

Intervention Type DRUG

paclitaxel Injection:5ml:100 mg/m2(80 mg/m2 or 60 mg/m2 can be used if necessary),Q3W,on the first and eighth day of the treatment cycle for up to 2 years

Interventions

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LVGN6051 Monoclonal Antibody Injection

LVGN6051 Monoclonal Antibody Injection:1 mg/kg or 2 mg/kg, every 3 weeks(Q3W) , on the first day of the treatment cycle for up to 2 years.

Intervention Type BIOLOGICAL

toripalimab Injection

toripalimab Injection: 240mg fixed dose,Q3W, on the first day of the treatment cycle for up to 2 years.

Intervention Type BIOLOGICAL

Paclitaxel injection

paclitaxel Injection:5ml:100 mg/m2(80 mg/m2 or 60 mg/m2 can be used if necessary),Q3W,on the first and eighth day of the treatment cycle for up to 2 years

Intervention Type DRUG

Other Intervention Names

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LVGN6051

Eligibility Criteria

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Inclusion Criteria

1. Age of 18 years or older on the date of signing the informed consent.
2. Understand and be willing to sign a written informed consent.
3. Patients with recurrent/metastatic head and neck squamous cell carcinoma confirmed by histology or cytology (the primary tumor is located in the oral cavity, oropharynx, hypopharynx, or larynx) that cannot be resected and cannot be cured by local treatment.
4. The status of head and neck squamous cell carcinoma meets one of the following requirements: a. There is still residual tumor, local recurrence, or metastatic cancer within 6 months after platinum-containing neoadjuvant treatment, adjuvant treatment, or curative concurrent chemoradiotherapy, or b. Any residual tumor, local recurrence, or metastatic cancer should receive first-line systemic therapy, but this first-line systemic therapy is not suitable for platinum-containing regimens.
5. Have measurable lesions as defined by the RECIST 1.1.
6. ECOG PS 0 or 1.
7. Life expectancy estimated at ≥3 months.
8. The functions of important organs within 1 week before the first dose meet all the following requirements: a. Hb ≥9.0 g/dL (90 g/L), b. ANC ≥1500/μL (1.5×109/L), c. Platelet count (PLT) ≥100,000/μL (100×109/L), d. Total bilirubin ≤ upper limit of normal laboratory value (ULN), e. AST ≤1.5× ULN and ALT ≤1.5× ULN, f. International normalized ratio (INR)/prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤1.5× ULN, g. Serum amylase and lipase ≤1.5× ULN, h. serum albumin ≥3.0 g/dL (30 g/L), and i. CCR ≥30 ml/min.
9. Female patients of childbearing potential should have a negative blood pregnancy test or urine pregnancy test within 72 hours before the first dose of study treatment.
10. Male patients should agree to take adequate contraceptive measures from the first dose of study treatment to 180 days after the last dose.

Exclusion Criteria

1. Have received drug treatment targeting CD137 (4-1BB) or paclitaxel injection.
2. Subjects who are suitable to receive curative-intent local treatment.
3. Have received any systemic anti-tumor treatment after disease recurrence or metastasis.
4. Failed to fully recover from the adverse events caused by the previous anti-tumor treatment within 2 weeks before receiving the first dose of study treatment (i.e., ≤ grade 1 or baseline).
5. At the first dose of study treatment, it is still within 5 half-lives of previous anti-cancer agents.
6. Have risk of rapidly progressive disease, immediate risk of massive bleeding, airway obstruction, or uncontrolled significant tumor pain that, in the opinion of the investigator, may impair compliance with study treatment.
7. Diagnosed with immunodeficiency or receiving systemic steroids or any other immunosuppressive treatments within 7 days before the first dose of study treatment. The use of inhaled, topical, or physiologic doses of corticosteroids is allowed, i.e., ≤10 mg/day of prednisone or equivalent.
8. Have other malignant tumors diagnosed and/or treated within 5 years before the first dose of study treatment, except for cured basal cell carcinoma of the skin, cured squamous cell carcinoma of the skin, resected uterine cervical carcinoma in situ, resected breast cancer in situ. Other exceptions can be discussed with the sponsor.
9. Known occurrence of active central nervous system (CNS) metastases and/or cancerous meningitis.
10. Have an active autoimmune disease that has required systemic treatment, such as disease-modifying agents, corticosteroids, or immunosuppressive drugs in the past 2 years. Replacement therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for hypothyroidism, adrenal insufficiency, pituitary insufficiency, etc.) are not considered systemic treatments.
11. Have previously received allogeneic tissue/organ transplantation or any cell therapy.
12. Currently suffering from active, non-infectious pneumonia or interstitial lung disease that requires treatment with oral or intravenous glucocorticoids.
13. Active infection requiring intravenous (IV) anti-infective drugs within the first 14 days before the first dose of study treatment or the presence of unhealed wounds or ulcers.
14. The investigator believes that any previous or existing medical condition, treatment, or laboratory test abnormality may affect the study results, interfere with the patient's participation in the entire study, or the study participation is not in the patient's best interest.
15. Female patients who are pregnant or nursing or who plan to become pregnant or give birth during the study period (i.e., from the beginning of the screening period to 180 days after the last treatment).
16. Patients known to have tested positive for human immunodeficiency virus (HIV) or known to have acquired immunodeficiency syndrome (AIDS).
17. Known to have active hepatitis B or hepatitis C.
18. Have received live virus vaccine within 30 days before the first dose of study treatment.
19. Have received systemic immune-stimulating drugs (e.g., IL-2, IFN-γ) within 4 weeks before the first dose of study treatment.
20. Clinically significant heart and CNS disorders, including acute myocardial infarction within 6 months before Cycle 1 Day 1, congestive heart failure as Class III or IV by the New York Heart Association, unstable angina, uncontrolled arrhythmias requiring further treatment, stroke, or brain hemorrhage. Subjects with arrhythmia who are treated with antiarrhythmic drugs and whose electrocardiogram (ECG) screening shows a controlled heart rhythm may be enrolled.
21. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.
22. Patients with a history of severe allergies may be allergic to the ingredients of the investigational drugs.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Lyvgen Biopharma Holdings Limited

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ye Guo

Role: PRINCIPAL_INVESTIGATOR

Shanghai Oriental Hospital

Locations

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Anhui Cancer Hospital

Hefei, Anhui, China

Site Status NOT_YET_RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status NOT_YET_RECRUITING

Beijing Tongren Hospital Affiliated to Capital Medical University

Beijing, Beijing Municipality, China

Site Status NOT_YET_RECRUITING

Fujian cancer hospital

Fuzhou, Fujian, China

Site Status NOT_YET_RECRUITING

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status NOT_YET_RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, China

Site Status RECRUITING

Henan cancer hospital

Zhengzhou, Henan, China

Site Status NOT_YET_RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status NOT_YET_RECRUITING

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status NOT_YET_RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, China

Site Status NOT_YET_RECRUITING

The Second Xiangya Hospital, Central South University

Changsha, Hunan, China

Site Status NOT_YET_RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status NOT_YET_RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status NOT_YET_RECRUITING

Liaoning cancer hospital

Shenyang, Liaoning, China

Site Status NOT_YET_RECRUITING

Shanghai Oriental Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Site Status NOT_YET_RECRUITING

Countries

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China

Central Contacts

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Yan Wang

Role: CONTACT

+86 15388232733

Facility Contacts

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Jin Gao

Role: primary

+86 15395005376

Yan Sun

Role: primary

+86 13671370026

Shurong Zhang

Role: primary

+86 13501085646

Sufang Qiu

Role: primary

+86 13609589163

Xiaoming Huang

Role: primary

+86 13602808820

Song Qu

Role: primary

+86 13607887386

Hui Wu

Role: primary

+86 13503716710

Kunyu Yang

Role: primary

+86 13995595360

Guangyuan Hu

Role: primary

+86 13886000095

Liangfang Shen

Role: primary

+86 13975805137

Ping Liu

Role: primary

+86 15084987287

Yaqian Han

Role: primary

+86 18673176667

Jinguan Lin

Role: primary

+86 13307318568

Xia Li

Role: primary

+86 189 0091 7377

Ye Guo

Role: primary

+86 13501678472

Lei Liu

Role: primary

+86 18980606231

Meiyu Fang

Role: primary

+86 13750851650

Other Identifiers

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LVGN6051-0402-HNSCC

Identifier Type: -

Identifier Source: org_study_id

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