Clinical trial NCT05149807: Clinical Study of SHR-1701 Plus Chemotherapy as Perioperative Treatment in Subjects With Gastric Cancer
Official title: A Randomized, Double-Blind, Multi-Center Phase II/III Clinical Study of PD-L1 Antibody/TGF-βRII (SHR-1701) Plus Tegafur Gimeracil Oteracil Potassium and Oxaliplatin Versus Placebo Plus Tegafur Gimeracil Oteracil Potassium and Oxaliplatin as Perioperative Treatment in Subjects With Resectable Gastric Cancer or Gastroesophageal Junction Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Perioperative Treatment in Subjects With Locally Advanced Resectable Gastric Cancer or Gastroesophageal Junction Cancer
Lead sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-12-08
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a multi-center phase II/III clinical study consisting of two stages: Stage I is a single-arm open-label phase II study to preliminarily explore the efficacy and safety of SHR-1701 plus S-1 and oxaliplatin; Stage II is a randomized, double-blind, multi-center phase III study of SHR-1701 plus S-1 and oxaliplatin versus placebo plus S-1 and oxaliplatin as perioperative treatment in subjects with resectable GC or GEJC.
Primary purpose: TREATMENT

Brief summary: This is a multi-center phase II/III clinical study consisting of two stages: Stage I is a single-arm open-label phase II study to preliminarily explore the efficacy and safety of SHR-1701 plus S-1 and oxaliplatin mainly by the endpoint of pCR rate.

Stage II is a randomized, double-blind, multi-center phase III study of SHR-1701 plus S-1 and oxaliplatin versus placebo plus S-1 and oxaliplatin as perioperative treatment in subjects with resectable GC or GEJC. A total of 846 treatment naïve subjects will be enrolled, and primary endpoint of this stage is Independent Review Committee (IRC)-assessed EFS.


Eligibility criteria: Inclusion Criteria:

1. Pathologically diagnosed with GC or GEJC, histologically confirmed to be adenocarcinoma, and have no previous anti-tumor treatments for GC or GEJC.
2. Aged 18 or above, male or female.
3. Be suitable for (investigator's assessment) and planning to undergo neoadjuvant therapy + radical surgery with curative intent before entering into the study.
4. locally advanced Gastric Cancer or Gastroesophageal Junction Cancer confirmed by investigator.
5. Be able to provide tumor tissue blocks.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
7. Life expectancy of ≥ 6 months.
8. Have adequate organ and bone marrow functions.
9. Women without childbearing potential refer to post-menopausal women, or women who underwent bilateral oophorectomy with medical records. Male subjects and female subjects of childbearing potential must agree to take a medically approved contraceptive measure (refer to Appendix 4) during the study, within 3 months after the last dose of investigational product (SHR-1701), and within 9 months after the last dose of chemotherapy agents (S-1 and oxaliplatin); have a negative serum pregnancy test result within 3 days prior to the start of study treatment and not be breastfeeding.
10. Subjects must agree and have signed the informed consent form, be willing and able to follow the scheduled visits, study treatment, laboratory tests, and other study procedures.

Exclusion Criteria:

1. Have known squamous cell carcinoma, undifferentiated carcinoma, or other histological types of gastric cancer, or adenocarcinoma mixed with gastric cancer of other histological types.
2. Have unresectable factors, including unresectable tumors or contraindications to surgery or refusal of surgery.
3. Have more than 20% weight loss within 2 months prior to enrollment or randomization.
4. Have previously received some treatments or medications including anti-tumor treatments.
5. Diagnosed with other malignant tumors within 5 years prior to enrollment.
6. Have any active, known, or suspected autoimmune disease.
7. Have clinically significant bleeding symptoms or clear bleeding tendency within 3 months prior to enrollment or randomization; have gastrointestinal perforation and/or gastrointestinal fistula within 6 months prior to enrollment or randomization; have arterial/venous thrombotic events within 6 months prior to enrollment or randomization.
8. Have major vascular disease within 6 months prior to enrollment or randomization.
9. Have severe, unhealed, or dehisced wounds and active ulcers or untreated fractures.
10. Have intestinal obstruction and/or clinical signs or symptoms of gastrointestinal obstruction within 6 months prior to enrollment or randomization.
11. Have interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic disease.
12. Have known allergies to the study drug or their excipients; have severe allergic reactions to other monoclonal antibodies.
13. Have HIV infection or known AIDS, active untreated hepatitis or co-infection with hepatitis B and C.
14. Have uncontrolled cardiac symptoms or disease:
15. Have received systemic antibiotics for ≥ 7 days within 4 weeks prior to enrollment or randomization, or have unexplained fever \> 38.5 °C during screening or before the first dose.
16. Have known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
17. Have been screened for other clinical studies but failed the screening because PD-L1 expression did not meet the inclusion criteria or met the exclusion criteria; have participated in clinical studies of any other drugs, less than 4 weeks or 5 half-lives of the drug between the last dose of these study treatments and enrollment/randomization for this study (whichever is longer).
18. Have a known history of psychotropic substance abuse or drug abuse.
19. Have other severe physical or psychiatric disorders or laboratory abnormalities, which may increase the risk of participation in this study or interfere with the study results, or deemed unsuitable by the investigator.

Primary outcomes:
measure: Phase II : Pathological Complete Response pCR rate.
timeFrame: Up to approximately 23 months
measure: Phase III : Event-free Survival (EFS)
timeFrame: Up to approximately 57 months
Secondary outcomes:
measure: Disease-free Survival (DFS).
timeFrame: Up to approximately 57 months
measure: Preoperative Objective Response Rate (ORR).
timeFrame: Up to approximately 57 months
measure: Major pathological response (MPR) rates.
timeFrame: Up to approximately 23 months
measure: R0 resection rate
timeFrame: Up to approximately 23 months
measure: Overall Survival (OS).
timeFrame: Up to approximately 57 months
measure: Percentage of Participants Who Experience One or More Adverse Events (AEs).
timeFrame: Up to approximately 57 months
measure: 30-day postoperative mortality.
timeFrame: Up to approximately 24 months
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Hefei
country: China
facility: The Second Affiliated Hospital Of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Medical University Union Hospital
state: Fujian
city: Guangzhou
country: China
facility: Southern Medical University NanFang Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital, Sun Yat-sen University
state: Guangdong
city: Shijiazhuang
country: China
facility: The Fourth Hospital of Hebei Medical University
state: Hebei
city: Xingtai
country: China
facility: Xingtai People's Hospital
state: Hebei
city: Anyang
country: China
facility: Anyang Cancer Hospital
state: Henan
city: Luoyang
country: China
facility: The First Affiliated Hospital of Henan University of Science & Technology
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Hubei Cancer Hospital
state: Hubei
city: Yangzhou
country: China
facility: Subei people's Hospital of Jiangsu Province
state: Jiangsu
city: Shenyang
country: China
facility: Liaoning Cancer Hospital&Institute
state: Liaoning
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Air Force Military University Tangdu Hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Cancer Hospital & Institute
state: Sichuan
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
state: Tianjin
Study officials:
References: