Trial Title:
Induction IBI110 and Sintilimab With Chemotherapy In LA HNSCC
NCT ID:
NCT06494943
Condition:
Head and Neck Cancer
Head and Neck Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Squamous Cell Carcinoma of Head and Neck
Paclitaxel
Cisplatin
Conditions: Keywords:
Immune checkpoint inhibitor
Neoadjuvant chemotherapy
Induction chemotherapy
PD-1 inhibitor
LAG-3 inhibitor
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Active, not recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Sintilimab
Description:
PD-1 inhibitor
Arm group label:
Dose escalation phase
Arm group label:
Fixed-dose expansion phase
Intervention type:
Drug
Intervention name:
IBI110
Description:
LAG-3 inhibitor
Arm group label:
Dose escalation phase
Arm group label:
Fixed-dose expansion phase
Intervention type:
Drug
Intervention name:
Paclitaxel
Description:
Chemotherapy
Arm group label:
Dose escalation phase
Arm group label:
Fixed-dose expansion phase
Intervention type:
Drug
Intervention name:
Cis Platinum
Description:
Chemotherapy
Arm group label:
Dose escalation phase
Arm group label:
Fixed-dose expansion phase
Intervention type:
Procedure
Intervention name:
Surgery
Description:
Definitive surgery
Arm group label:
Dose escalation phase
Arm group label:
Fixed-dose expansion phase
Intervention type:
Radiation
Intervention name:
Adjuvant radiation
Description:
Adjuvant radiotherapy or chemoradiotherapy based on post-operative pathologic findings.
Arm group label:
Dose escalation phase
Arm group label:
Fixed-dose expansion phase
Summary:
This study aims to investigate the efficacy and safety of combining IBI110 and sintilimab
with the TP regimen for neoadjuvant chemotherapy in resectable locally advanced head and
neck squamous cell carcinoma (HNSCC).
Detailed description:
The NCCN guidelines recommend that for resectable locally advanced HNSCC, the recommended
treatment include surgery combined with postoperative adjuvant radiotherapy
(chemoradiotherapy), or concurrent chemoradiotherapy; for locally extensive HNSCC, the
guidelines recommend considering neoadjuvant chemotherapy, with subsequent selection of
surgery or chemoradiotherapy based on the efficacy of the neoadjuvant chemotherapy. In
recent years, multiple studies have shown that combining PD-1 inhibitors with neoadjuvant
chemotherapy may help improve the pathological response rate of surgical resection.
LAG-3 (Lymphocyte Activation Gene 3) is a cell surface molecule co-expressed with CD4 and
CD8 on activated CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic
cells. LAG-3 is an activation-induced T cell receptor (TCR) co-receptor with high
affinity for major histocompatibility complex (MHC) class II molecules, and it can
directly inhibit TCR signal transduction in the immune response through its interaction
with MHC II.
IBI110 can directly bind to LAG-3 on T cells, blocking the interaction between LAG-3 and
MHC II, thereby relieving the inhibitory effect of LAG-3 on T cell activation and
enhancing the anti-tumor immune response of T cells. Additionally, LAG-3 and PD-1 are
both immune checkpoint receptors. Co-inhibition of LAG-3 and PD-1 can enhance immune
responses and inhibit tumor growth. Therefore, IBI110 and its combination therapy with
PD-1 monoclonal antibodies have great development potential in the treatment of locally
advanced, recurrent, and late-stage solid tumors.
Based on the aforementioned foundation, this study intends to enroll patients with
resectable locally advanced head and neck squamous cell carcinoma (HNSCC). The treatment
protocol will involve neoadjuvant therapy with IBI110 and sintilimab, combined with the
TP regimen (docetaxel and cisplatin) for neoadjuvant chemotherapy. Following neoadjuvant
therapy, patients will undergo radical surgery, and adjuvant radiotherapy
(chemoradiotherapy) will be administered postoperatively based on pathological risk
factors as appropriate. The primary endpoints of the study are efficacy and safety.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Signed informed consent and willing to complete the study as per the protocol;
2. Age ≥ 18 years and ≤ 75 years;
3. Histologically confirmed head and neck squamous cell carcinoma, including primary
sites in the oropharynx, oral cavity, larynx, and hypopharynx;
4. Resectable locally advanced head and neck squamous cell carcinoma (AJCC 8th edition:
Stage III-IVB);
5. At least one measurable lesion before treatment, meeting the RECIST 1.1 criteria for
"measurable disease";
6. Expected survival > 3 months;
7. ECOG performance status 0-1;
8. Adequate organ function meeting the following criteria:
1. Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
2. Platelet count ≥ 100 × 10^9/L;
3. Hemoglobin ≥ 9 g/dL;
4. Serum albumin ≥ 2.8 g/dL;
5. Total bilirubin ≤ 1.5 × ULN, ALT, AST, and/or ALP ≤ 3 × ULN;
6. Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 60 mL/min
(Cockcroft-Gault, see Appendix III);
7. Activated partial thromboplastin time (APTT) and international normalized ratio
(INR) ≤ 1.5 × ULN (Patients on stable doses of anticoagulants such as
low-molecular-weight heparin or warfarin with INR within the therapeutic range
may be screened);
9. Patients with HBV infection and inactive/asymptomatic HBV carriers, or those with
chronic or active HBV, may be enrolled if HBV DNA < 500 IU/mL (or 2500 copies/mL) at
screening. Patients with positive HCV antibodies may be enrolled if HCV-RNA is
negative at screening;
10. Women of childbearing potential must have a negative urine or serum pregnancy test
within 7 days before treatment and use medically accepted contraception (e.g.,
intrauterine device, contraceptive pills, or condoms) during the study and for at
least 3 months after the last dose of sintilimab and 6 months after the last dose of
chemotherapy;
11. Non-sterilized male participants must agree to use medically accepted contraception
(e.g., intrauterine device, contraceptive pills, or condoms) during the study and
for at least 3 months after the last dose of toripalimab and 6 months after the last
dose of chemotherapy.
Exclusion Criteria:
Participants will be excluded from the study if they meet any of the following criteria:
1. History of or concurrent other malignancies (excluding those that have been cured
with a cancer-free survival period of more than 5 years, such as basal cell
carcinoma of the skin, carcinoma in situ of the cervix, and papillary thyroid
carcinoma);
2. Receipt of any of the following treatments:
1. Any investigational drug within 4 weeks prior to the first use of the study
drug;
2. Concurrent participation in another clinical study, unless it is an
observational (non-interventional) clinical study;
3. Systemic treatment with corticosteroids (daily dose >10 mg prednisone
equivalent) or other immunosuppressive drugs within 2 weeks before the first
use of the study drug, except for corticosteroids used for local inflammation
and prevention of allergies, nausea, and vomiting. Special cases need to be
discussed with the investigator. Inhaled or topical steroids and adrenal
corticosteroid replacement therapy with doses >10 mg/day prednisone equivalent
are allowed in the absence of active autoimmune disease;
4. Anti-tumor vaccination or live vaccination within 4 weeks prior to the first
administration of the study drug (for COVID-19 vaccination, the interval
between vaccination and treatment should be more than 2 weeks);
5. Major surgery or severe trauma within 4 weeks prior to the first use of the
study drug;
3. Uncontrolled cardiac clinical symptoms or diseases, such as:
1. Heart failure of NYHA class II or higher;
2. Unstable angina;
3. Myocardial infarction within 1 year;
4. Clinically significant supraventricular or ventricular arrhythmias requiring
clinical intervention;
4. Severe infections (CTCAE > Grade 2) within 4 weeks before the first use of the study
drug, such as severe pneumonia requiring hospitalization, bacteremia, or
complications of infections. Baseline chest imaging indicating active pulmonary
inflammation, symptoms and signs of infection within 4 weeks prior to the first use
of the study drug, or requiring oral or intravenous antibiotics;
5. Active autoimmune diseases or a history of autoimmune diseases (such as interstitial
pneumonia, colitis, hepatitis, pituitary inflammation, vasculitis, nephritis,
hyperthyroidism, hypothyroidism, including but not limited to these diseases or
syndromes); except for autoimmune-mediated hypothyroidism treated with a stable dose
of thyroid replacement hormone, type 1 diabetes with a stable dose of insulin,
vitiligo, or childhood asthma/allergies that have resolved without intervention in
adulthood;
6. History of immunodeficiency, including positive HIV test, other acquired or
congenital immunodeficiency diseases, or history of organ transplantation and
allogeneic bone marrow transplantation;
7. History of interstitial lung disease (excluding radiation pneumonitis that did not
require steroid treatment) or non-infectious pneumonia;
8. Active pulmonary tuberculosis infection identified by history or CT scan, or a
history of active pulmonary tuberculosis infection within 1 year prior to
enrollment, or a history of active pulmonary tuberculosis infection more than 1 year
ago but without formal treatment;
9. Participants with active hepatitis B (HBV DNA ≥500 IU/mL or 2500 copies/mL) or
hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of
detection by the assay);
10. Known history of psychiatric drug abuse, alcoholism, or drug addiction;
11. Pregnant or breastfeeding women;
12. Other factors deemed by the investigator that could lead to forced early termination
of the study, such as severe concomitant disease (including mental illness)
requiring combined treatment, severely abnormal laboratory test values, or family or
social factors that may affect the safety of the participant or the collection of
trial data.
Gender:
All
Gender based:
Yes
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Fudan University Shanghai Cancer Center
Address:
City:
Shanghai
Zip:
200032
Country:
China
Start date:
June 26, 2024
Completion date:
December 31, 2028
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06494943
