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

A Phase 2 Study of LVGN6051 Combined With Toripalimab and Paclitaxel for Recurrent/Metastatic HNSCC Rapidly Progressed From Previous Platinum-containing Curative Treatment or Contraindicated for Platinum-containing Treatment

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Biological: LVGN6051 Monoclonal Antibody Injection; Biological: toripalimab Injection; Drug: Paclitaxel injection

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230000
      • Anhui Cancer Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Tongren Hospital Affiliated to Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450008
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430000
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University
    • Changsha, Hunan, China, 410031
      • Hunan Cancer Hospital
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital, Central South University
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Liaoning Cancer Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200123
      • Shanghai Oriental Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: LVGN6051combined with toripalimab and paclitaxel; LVGN6051 in combination with toripalimab and paclitaxel

Biological: 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.; Other Names: LVGN6051; Biological: toripalimab Injection; toripalimab Injection: 240mg fixed dose,Q3W, on the first day of the treatment cycle for up to 2 years.; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
to determine objective response rate (ORR)	The anti-tumor activity of LVGN6051 combined with toripalimab and paclitaxel will be evaluated by independent central review (ICR) according to RECIST 1.1 for objective response rate (ORR). (Part 2)	through study completion, an average of 30 months
to determine treatment-related adverse events (TRAEs, the safety and tolerability of two preset dose levels )	The safety and tolerability of two preset dose levels based on treatment-related adverse events (TRAEs), including dose-limiting toxicities(DLTs )and serious adverse events (SAEs), through a "safety run-in" to determine the Part 2 therapeutic dose of LVGN6051 in combination with toripalimab and paclitaxel. (Part 1)	6 months

Collaborators and Investigators

• Sponsor: Lyvgen Biopharma Holdings Limited
• Investigators: Principal Investigator: Ye Guo, Shanghai Oriental Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: April 12, 2024
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Paclitaxel; toripalimab
• Other Study ID Numbers: LVGN6051-0402-HNSCC

Drug and device information, study documents

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