Clinical trial NCT04139135: A Clinical Study of HLX10 Combined With Chemotherapy Versus Placebo Combined With Chemotherapy for Neoadjuvant/Adjuvant Treatment of Gastric Cancer
Official title: A Randomized, Double-blinded, Multicenter, Phase III Clinical Study of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) Combined With Chemotherapy Versus Placebo Combined With Chemotherapy for Neoadjuvant/Adjuvant Treatment of Gastric Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Gastric Cancer
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2019-10-25
Enrollment: 642
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a two-arm, randomized, double-blinded, multicenter phase III clinical study to evaluate the efficacy of HLX10 combined with chemotherapy versus placebo combined with chemotherapy for neoadjuvant/adjuvant treatment of gastric cancer.

Subjects will be randomized to the following two arms at 1: 1 ratio:

* Arm A (HLX10 arm): HLX10 combined with chemotherapy will be adopted in the neoadjuvant treatment phase, and HLX10 monotherapy will be administered in the adjuvant treatment phase;
* Arm B (control arm): Placebo combined with chemotherapy will be given in the neoadjuvant treatment phase, and chemotherapy alone will be administered during the adjuvant treatment phase.

Chemotherapy regimen SOX (oxaliplatin + tegafor gimeracil oteracil potassium (S-1)) will be used in the neoadjuvant treatment phase in Arm A and B, and in the adjuvant treatment phase in Arm B.

After randomization, subjects will receive a total of 3 cycles of neoadjuvant treatment with the mentioned treatment regimen.Surgery will be performed within 3-6 weeks after the last cycle of neoadjuvant treatment.All subjects who have completed the surgery will be unblinded after surgery, and adjuvant treatment will be started 3 to 12 weeks after surgery. Subjects randomized to Arm A (HLX10 arm) will continue to receive HLX10 monotherapy for up to 17 cycles (12 months).Subjects in Arm B after surgery (control arm) will continue to use chemotherapy alone (oxaliplatin + S-1) for 5 cycles.


Eligibility criteria: Inclusion Criteria:

1. Voluntary participation in the clinical study; fully understands and is informed of the study and has signed the Informed Consent Form (ICF); willing to comply with and able to complete all trial procedures.
2. The gender is not limited. When ICF is signed, the age is ≥ 18 years and ≤ 70 years old.
3. Histologically confirmed untreated gastric cancers, mainly adenocarcinoma.
4. Within 4 weeks prior to first dose, determined by the Independent Radiology Review Committee (IRRC) as: ≥ T3 and number of lymph node metastases ≥ 1 and no distant metastasis.
5. Prior to enrollment, the attending physician will evaluate to determine the eligibility for a R0 resection for the purpose of radical treatment.
6. Have good cardiac function and can be treated with radical resection.
7. tumor specimen testing results are PD-L1 positive (CPS ≥5). Subjects must provide the tumor tissues at screening or in the investigated surgery (if any), for PD-L1 expression level assessment.
8. Within 7 days before the first use of the study drug, ECOG: 0 \~ 1;
9. Expected survival 12 weeks;
10. The functions of the vital organs meet requirements.

Exclusion Criteria:

1. Existence of other active malignant tumors within 5 years or at the same time.
2. Plan to perform or have undergone an organ or bone marrow transplant.
3. Myocardial infarction and poorly controlled arrhythmias occurred within 6 months prior to the first dose.
4. Existence of grade III - IV cardiac disorders defined by the NYHA or echocardiogram shows: LVEF (left ventricular ejection fraction) \< 50%.
5. Human immunodeficiency virus (HIV) infection.
6. Patients with active tuberculosis.
7. Patient with previous or current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia, severely impaired lung function, etc.
8. Patients who have previously received other antibody/drug treatments for immune checkpoints, such as PD-1, PD-L1, and CTLA4 treatments.
9. Have diseases that may increase the risk of participating in the study and using the study medications, or other severe, acute, and chronic diseases and therefore are judged by the investigator to be unsuitable for clinical studies.

Primary outcomes:
measure: EFS
timeFrame: from randomizationuntil firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 3 years
Secondary outcomes:
measure: EFS
timeFrame: from randomizationuntil firstly confirmed and recorded disease progression or death (whichever occurs earlier)，assessed up to 3 years
measure: DFS
timeFrame: from the start of surgery to disease recurrence or death (for any reason)，assessed up to 3 years
measure: pCR rate
timeFrame: after surgery，an average of 6 months
measure: 5-year OS rate
timeFrame: OS is the time from randomization to death (of any cause)，assessed up to 5 years
Other outcomes:
Locations:
city: Shenzhen
country: China
facility: Peking University shenzhen hospital
state: Guangdong
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: China PLA General Hospital
city: Beijing
country: China
facility: Peking University International Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
city: Cangzhou
country: China
facility: Cangzhou People's Hospital
city: Hefei
country: China
facility: Anhui Provincial Hospital
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University
city: Linyi
country: China
facility: Linyi Cancer Hospital
city: Shijia Zhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
city: Taiyuan
country: China
facility: Shanxi Provincial People's Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Institute & Hospital
city: Xingtai
country: China
facility: Xingtai People's Hospital
Study officials:
References: