Trial Title:
A Study of LVGN6051 Combination Therapy in Patient With Head and Neck Squamous Cell Carcinoma (HNSCC)
NCT ID:
NCT06378177
Condition:
Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Paclitaxel
Antibodies
Antibodies, Monoclonal
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Sequential Assignment
Intervention model description:
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 purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
LVGN6051 Monoclonal Antibody Injection
Description:
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.
Arm group label:
LVGN6051combined with toripalimab and paclitaxel
Other name:
LVGN6051
Intervention type:
Biological
Intervention name:
toripalimab Injection
Description:
toripalimab Injection: 240mg fixed dose,Q3W, on the first day of the treatment cycle for
up to 2 years.
Arm group label:
LVGN6051combined with toripalimab and paclitaxel
Intervention type:
Drug
Intervention name:
Paclitaxel injection
Description:
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
Arm group label:
LVGN6051combined with toripalimab and paclitaxel
Summary:
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:
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Anhui Cancer Hospital
Address:
City:
Hefei
Zip:
230000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jin Gao
Phone:
+86 15395005376
Email:
gj11667@126.com
Facility:
Name:
Beijing Cancer Hospital
Address:
City:
Beijing
Zip:
100142
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yan Sun
Phone:
+86 13671370026
Email:
13671370026@139.com
Facility:
Name:
Beijing Tongren Hospital Affiliated to Capital Medical University
Address:
City:
Beijing
Zip:
100730
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Shurong Zhang
Phone:
+86 13501085646
Email:
13501085646@163.com
Facility:
Name:
Fujian cancer hospital
Address:
City:
Fuzhou
Zip:
350014
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Sufang Qiu
Phone:
+86 13609589163
Email:
sfqiu@126.com
Facility:
Name:
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Address:
City:
Guangzhou
Zip:
510120
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xiaoming Huang
Phone:
+86 13602808820
Email:
xiaoming.huang@126.com
Facility:
Name:
Guangxi Medical University Cancer Hospital
Address:
City:
Nanning
Zip:
530021
Country:
China
Status:
Recruiting
Contact:
Last name:
Song Qu
Phone:
+86 13607887386
Email:
13607887386@163.com
Facility:
Name:
Henan cancer hospital
Address:
City:
Zhengzhou
Zip:
450008
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Hui Wu
Phone:
+86 13503716710
Email:
wuhui7008@126.com
Facility:
Name:
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430000
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Kunyu Yang
Phone:
+86 13995595360
Email:
yangky71@aliyun.com
Facility:
Name:
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Guangyuan Hu
Phone:
+86 13886000095
Email:
h.g.y.121@163.com
Facility:
Name:
Xiangya Hospital Central South University
Address:
City:
Changsha
Zip:
410008
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Liangfang Shen
Phone:
+86 13975805137
Email:
slf1688@sina.com
Facility:
Name:
The Second Xiangya Hospital, Central South University
Address:
City:
Changsha
Zip:
410011
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Ping Liu
Phone:
+86 15084987287
Email:
cyril0820@sina.com
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410031
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Yaqian Han
Phone:
+86 18673176667
Email:
hanyaqiancs@163.com
Facility:
Name:
Hunan Cancer Hospital
Address:
City:
Changsha
Zip:
410031
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Jinguan Lin
Phone:
+86 13307318568
Email:
xjl5027@easthospital.com
Facility:
Name:
Liaoning cancer hospital
Address:
City:
Shenyang
Zip:
110042
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Xia Li
Phone:
+86 189 0091 7377
Email:
lixiadoctor@163.com
Facility:
Name:
Shanghai Oriental Hospital
Address:
City:
Shanghai
Zip:
200123
Country:
China
Status:
Recruiting
Contact:
Last name:
Ye Guo
Phone:
+86 13501678472
Email:
pattrickguo@gmail.com
Facility:
Name:
West China Hospital of Sichuan University
Address:
City:
Chengdu
Zip:
610041
Country:
China
Status:
Recruiting
Contact:
Last name:
Lei Liu
Phone:
+86 18980606231
Email:
32498600@qq.com
Facility:
Name:
Zhejiang Cancer Hospital
Address:
City:
Hangzhou
Zip:
310022
Country:
China
Status:
Not yet recruiting
Contact:
Last name:
Meiyu Fang
Phone:
+86 13750851650
Email:
fangmy@zjcc.org.cn
Start date:
June 21, 2024
Completion date:
October 31, 2027
Lead sponsor:
Agency:
Lyvgen Biopharma Holdings Limited
Agency class:
Industry
Source:
Lyvgen Biopharma Holdings Limited
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06378177
