PD1 Combined With Chemotherapy for Adjuvant Treatment of Gastric Cancer

• Sponsor: Shanghai Junshi Bioscience Co., Ltd. (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05180734
• Collaborator: (none)
• Enrollment: 680
• Locations: 54
• Arms: 2
• Anticipated Duration (Months): 78.4
• Patients Per Site: 12.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

"This is an international, multicenter, randomized, double-blind phase III study, plans to recruit 680 patients who received radical gastrectomy (R0, D2 or higher lymphadenectomy) with postoperative pathological stage II (T4aN0M0) or III (the 8th Edition American Joint Committee on Cancer [AJCC] Cancer Staging Manual) gastric adenocarcinoma and gastroesophageal junction adenocarcinoma, and the study intends to evaluate the efficacy and safety of JS001 combined with postoperative adjuvant chemotherapy versus placebo combined with postoperative adjuvant chemotherapy.

Patients meeting the inclusion criteria will be 1:1 randomized into JS001-chemotherapy group and placebo-chemotherapy group. The random stratification factors include adjuvant chemotherapeutic regimens (XELOX versus SOX) and tumor anatomical sites (gastric adenocarcinoma versus gastroesophageal junction adenocarcinoma). "

Condition or Disease	Intervention/Treatment	Phase
Gastric or Gastroesophageal Junction Adenocarcinoma	Biological: JS001/Placebo; Biological: JS001/placebo combine with Postoperative Adjuvant Chemotherapy	Phase 3

Detailed Description

"This is an international, multicenter, randomized, double-blind phase III study, plans to recruit 680 patients who received radical gastrectomy (R0, D2 or higher lymphadenectomy) with postoperative pathological stage II (T4aN0M0) or III (the 8th Edition American Joint Committee on Cancer [AJCC] Cancer Staging Manual) gastric adenocarcinoma and gastroesophageal junction adenocarcinoma, and the study intends to evaluate the efficacy and safety of JS001 combined with postoperative adjuvant chemotherapy versus placebo combined with postoperative adjuvant chemotherapy.

Patients meeting the inclusion criteria will be 1:1 randomized into JS001-chemotherapy group and placebo-chemotherapy group. The random stratification factors include adjuvant chemotherapeutic regimens (XELOX versus SOX) and tumor anatomical sites (gastric adenocarcinoma versus gastroesophageal junction adenocarcinoma).

The study treatment will be initiated 4-6 weeks after surgery, and the investigator will select XELOX (Oxaliplatin + capecitabine) or SOX (Oxaliplatin + S-1, tegafur, gimeracil and oteracil potassium) as the adjuvant chemotherapeutic regimen given as 3-week cycles for up to 8 cycles based on each patient's condition; JS001/placebo will be given for up to 17 cycles after surgery, until intolerable toxicity, disease recurrence, patient's withdrawal of consent, investigator's judgment that the patient needs to be withdrawn from the study treatment, or death, whichever comes first.

Safety evaluation, including vital signs, ECOG score, physical examination and laboratory examinations, will be performed on a regular basis during the treatment.

This study will end after the main analysis node of DFS and unblinding for analysis are achieved, or 5 years after enrollment of the last patient, whichever comes first. The Sponsor is entitled to terminate the study at any time due to specific reasons (e. g, major safety issues, force majeure, etc.).

Radiological follow-up: tumor response evaluation will be performed once every 12 weeks ±7 days within the first 5 years after randomization, and once per year subsequently, until disease recurrence or death. When symptoms or signs of suspected recurrence/metastasis occur, the radiological evaluation can be performed at any time. Disease recurrence is defined as local recurrence or distant metastases with clear radiological evidence (CT or MRI).

Survival follow-up: it will be performed once every 12 weeks after disease recurrence, until patient's withdrawal of informed consent, loss to follow-up or death, whichever comes first.

Safety follow-up: adverse events will be closely followed up and recorded, until 60 days after the last dose of treatment or the end of study follow-up (death, loss to follow-up, withdrawal of consent form and the end of study), whichever comes first.

"

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 680 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: An International, Multicenter, Randomized, Double-blind, Phase III Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection Combined With Postoperative Adjuvant Chemotherapy Versus Placebo Combined With Postoperative Adjuvant Chemotherapy in Patients With Gastric or Gastroesophageal Junction Adenocarcinoma After Radical Gastrectomy
• Actual Study Start Date: Jan 19, 2022
• Anticipated Primary Completion Date: Mar 31, 2026
• Anticipated Study Completion Date: Jul 31, 2028

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JS001 240mg, Q3W with XELOX regimen or SOX regimen JS001 240mg, will be intravenously administered once every 3 weeks, until 17 cycles XELOX regimen (oxaliplatin + capecitabine) or SOX regimen (oxaliplatin + S-1), given in one therapeutic cycle of 3 weeks for up to 8 cycles XELOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; capecitabine, 1000mg/m2, orally, twice per day, from day 1 to day 14, Q3W. SOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; S-1 Capsules, 40-60mg, orally, twice per day, from day 1 to day 14, Q3W.	Biological: JS001/Placebo; JS001/placebo combine with Postoperative Adjuvant Chemotherapy; Other Names: Postoperative Adjuvant Chemotherapy
Placebo Comparator: Placebo combine with chemotherapy XELOX regimen (oxaliplatin + capecitabine) or SOX regimen (oxaliplatin + S-1), given in one therapeutic cycle of 3 weeks for up to 8 cycles XELOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; capecitabine, 1000mg/m2, orally, twice per day, from day 1 to day 14, Q3W. SOX regimen: Oxaliplatin, 130mg/m2, intravenous drip for over 3 hours, day 1, Q3W; S-1 Capsules, 40-60mg, orally, twice per day, from day 1 to day 14, Q3W.	Biological: JS001/placebo combine with Postoperative Adjuvant Chemotherapy; JS001/placebo combine with Postoperative Adjuvant Chemotherapy; Other Names: Postoperative Adjuvant Chemotherapy

Outcome Measures

Primary Outcome Measures

1. DFS evaluated by the investigator based on RECIST v1.1 [Through study completion, average of 60 months]

   To evaluate the disease-free survival (DFS) in accordance with RECIST v1.1 evaluated by the blind independent central review (BICR) for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

Secondary Outcome Measures

1. DFS evaluated by the investigator based on RECIST v1.1 [Through study completion, average of 60 months]

   To evaluate the disease-free survival (DFS) evaluated by the investigator for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

2. DFS rate at 3 years evaluated by the BICR based on RECIST v1.1 [36 months]

   To evaluate the postoperative DFS rate and overall survival (OS) rate at 3 years for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

3. DFS rate at 5 years evaluated by the BICR based on RECIST v1.1 [60 months]

   To evaluate the postoperative DFS rate and overall survival (OS) rate at 5 years for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

4. OS [5 years]

   To evaluate the OS for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

5. Overall survival rate (OS rate) at 3 years and 5 years [3 years and 5 years]

   To evaluate the postoperative overall survival (OS) rate at 3 for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

6. Time to local recurrence (TTLR) [Through study completion, average of 60 months]

   To evaluate the time to local recurrence (TTLR) for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

7. Time to response (TTR) [Through study completion, average of 60 months]

   To evaluate thetime to recurrence (TTR) for Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

8. Incidence and severity of adverse events (AE),clinically significant abnormal changes in vital signs, ECOG scores, physical examination, electrocardiogram (ECG), echocardiography and laboratory examinations [Through study completion, average of 60 months]

   To evaluate the safety of Toripalimab Injection (JS001) combined with adjuvant chemotherapy versus placebo combined with adjuvant chemotherapy in patients with gastric or gastroesophageal junction adenocarcinoma after radical gastrectomy.

9. To explore the correlation of PD-L1 status, tumor mutation burden (TMB) status, microsatellite status and EBV status with DFS, DFS rate , OS, OS rate at ,TTLR and TTR[efficacy] of adjuvant therapy. [Within 6 Months after C1D1]

   To evaluate the correlation of PD-L1 status, tumor mutation burden (TMB) status, microsatellite status and EBV status with the efficacy of adjuvant therapy.

10. To evaluate the potential correlation of the incidence of ADA of Toripalimab Injection (JS001) with incidence and severity of adverse events (AE)[safety] and DFS, DFS rate , OS, OS rate ,TTLR and TTR[efficacy]. [At every other cycle（each cycle is 21 days）up to 17 cycles]

    To evaluate the incidence and titer of anti-drug antibody (ADA) of Toripalimab Injection (JS001).

11. To evaluate the quality of life in the two groups using the EORTC QLQ-C30 questionnaires [From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 1 approximately years]

    To evaluate the disease-related symptoms and health-related quality of life (HRQoL) in the two groups through the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life questionnaire (EORTC QLQ-C30) a. The EORTC QLQ-C30 consists of three subscales with 30 questions. The EORTC QLQ-C30 have three subscales in the scale include functioning scales (15 questions), symptom scales (13 questions), and global health status (2 questions). The reliability and validity of Cronbach'α was 0.81-0.94. The functional scale and the global health status , the higher the total score, the better the quality of life; the lower the score in the symptom scale, the better the quality of life.

12. To evaluate the quality of life in the two groups using the EORTC QLQ-STO22 questionnaires [From date of randomization, until disease progression , loss of clinical benefit ,withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Up to 1 approximately years]

    To evaluate the disease-related symptoms and health-related quality of life (HRQoL) in the two groups through the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Stomach (QLQ-STO22).The EORTC QLQ-STO22 consists of one subscale with 22 questions.The EORTC QLQ-STO22 scale include symptom scales (22 questions) The Cronbach'α was 0.70-0.94.The lower the score in the symptom scale, the better the quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

1. Age 18-75 years.

2. No residual tumor (R0) after D2 or greater lymphadenectomy through laparotomy.

3. According to the definition of the 8th edition of the AJCC Cancer Staging Manual, patients with gastric adenocarcinoma confirmed by histopathology, pathological stage II (T4aN0M0) and stage III, including gastroesophageal junction adenocarcinoma (GEJ) patients.

4. ECOG performance status 0-1.

5. No metastasis or recurrence as radiologically confirmed.

6. Patients must have adequate organ function as assessed in the laboratory tests.

7. Patients must provide informed consent for this study, and sign the written informed consent form voluntarily before the initiation of the study, and are willing and able to comply with the scheduled visits, treatment plan, laboratory examinations and other study procedures in the study.

8. Female patients of childbearing age must take a serum pregnancy test within 7 days before randomization with negative results, and agree to adopt reliable and effective contraceptive methods during the study.

4.2 EXCLUSION CRITERIA

1. Previous use of non-surgical therapy for gastric adenocarcinoma.

2. Having liver, peritoneal or distant metastasis.

3. Inability to take the drug orally.

4. Having postoperative complications that are not relieved at the time of randomization.

5. Uncontrolled pericardial effusion or pleural effusion which required invasive treatment, and grade II or above peritoneal effusion (diagnosed clinically) present at screening.

6. Presence of contraindicated chemotherapeutic drugs in this study and failure to receive the adjuvant therapeutic regimen in any group specified in the protocol.

7. Having received any surgery not for gastric adenocarcinoma requiring general anesthesia within 28 days prior to randomization.

8. Having malignant tumors other than gastric adenocarcinoma within 5 years before randomization.

9. Active autoimmune disorders requiring systemic treatment.

10. Patients with immunodeficiency or receiving long-term systemic steroid therapy.

11. Concurrent diverticulitis or symptomatic gastrointestinal ulcer disease.

12. Patients who are receiving or requiring anticoagulant therapy.

13. Patients with serious cardiovascular and cerebrovascular diseases.

14. Diabetes mellitus that is not effectively controlled.

15. Active infections requiring treatment.

16. ≥Grade 2 peripheral neuropathy.

17. Patients with active tuberculosis or having received anti-tuberculosis therapy within one year prior to randomization.

18. Patients currently having interstitial lung disease or having a history of interstitial lung disease.

19. Hepatitis B, known positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb), and HBV DNA≥1000cps/ml; hepatitis C, positive HCV RNA or RNA ≥1000cps/ml.

20. Human immunodeficiency virus (HIV) antibody positive.

21. Vaccination of any live vaccine within 4 weeks before randomization.

22. Previous allogeneic bone marrow transplantation or solid organ transplantation.

23. Previous treatment targeting PD-1 receptor or its ligand PD-L1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptor;

24. Previous history of serious allergy to monoclonal antibody or other biological preparations.

25. Having participated in other interventional clinical studies within 28 weeks before randomization.

26. Having clinically significant underlying medical disease that may affect administration of study drug or compliance to the protocol, as judged by investigators.

27. Other patients who are considered by investigators as inappropriate for enrollment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The First Affiliated Hospital of Bengbu Medical College	Bengbu	Anhui	China	233300
2	The Peple's Hospital of Chizhou	Chizhou	Anhui	China
3	Chinese PLA General Hospital	Beijing	Beijing	China	100000
4	Beijing Hospital	Beijing	Beijing	China	100005
5	Peking University People's hospital	Beijing	Beijing	China	100044
6	Beijing Friendship Hospital, Capital Medical University	Beijing	Beijing	China	100050
7	Beijing Cancer hospital	Beijing	Beijing	China	510515
8	The first affiliated hospital of chongqing medical universit	Chongqing	Chongqing	China	400016
9	Fujian Provincial Cancer Hospital	Fuzhou	Fujian	China	350011
10	The First Affiliated Hospital of Xiamen University	Xiamen	Fujian	China	361003
11	Gansu Provincial People's Hospital	Lanzhou	Gansu	China	730000
12	Lanzhou University Second Hospital	Lanzhou	Gansu	China	730000
13	Gansu Provincial Cancer Hospital	Lanzhou	Gansu	China	730050
14	The first Hospital of Lanzhou University	Lanzhou	Gansu	China	750050
15	Wuwei Cancer Hospital of Gansu Province	Wuwei	Gansu	China	733000
16	Guandong General Hospital	Guangzhou	Guandong	China	510000
17	Zhujiang Hospital of Southern Medical University	Guangzhou	Guandong	China	510280
18	The First People's Hospital of Foshan	Foshan	Guangdong	China	528000
19	The First Affiliated Hospital of Sun yat-sen University	Guangzhou	Guangdong	China	510080
20	Affiliated Cancer Hospital and Institute of Ghuangzhou Medical University	Guangzhou	Guangdong	China	510095
21	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong	China	510515
22	Peking University Shenzhen Hospital	Shenzhen	Guangdong	China	518000
23	Shenzhen People's Hospital	Shenzhen	Guangdong	China	518000
24	Guangxi Medical University Affiliated Tumor Hospital	Nanning	Guangxi	China	530021
25	The Fourth Hospital of Hebei Medical University	Shijiazhuang	Hebei	China	050011
26	Harbin Medical University Cancer Hospital	Harbin	Heilongjiang	China	150081
27	Henan cancer hospital	Zhengzhou	Henan	China	450003
28	The First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan	China	450052
29	Union Hospital, Tongji Medical College,Huazhong University of Science and Technology	Wuhan	Hubei	China	430022
30	Hubei Cancer Hospital	Wuhan	Hubei	China	430079
31	Xiangya Hospital Central South University	Changsha	Hunan	China	410008
32	Hunan Cancer Hopital	Changsha	Hunan	China	410031
33	Jiangsu cancer hospital	Nanjing	Jiangsu	China	210000
34	The first Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330006
35	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi	China	330006
36	The First Hospital of Jilin University	Changchun	Jilin	China	130021
37	The First Hospital of China Medical University	Shengyang	Liaoning	China	110000
38	LiaoNing Cancer Hospital & Institute	Shenyang	Liaoning	China	110000
39	General Hospital of Ningxia Medical University	Yinchuan	Ningxia	China	750000
40	Qinghai University Affiliated Hosptial	Xining	Qinghai	China	810000
41	Jinan Central Hospital	Jinan	Shangdong	China	250012
42	Shandong Provincial Hospital	Jinan	Shangdong	China	250031
43	Affiliated Hospital of Jining Medical University	Jining	Shangdong	China	272007
44	Zhongshan Hospital, Fudan university	Shanghai	Shanghai	China	200032
45	Shanghai General Hospital	Shanghai	Shanghai	China	200080
46	Shanxi Provincial People's Hospital	Taiyuan	Shanxi	China	030012
47	Tangdu hospital, Air force Military Medical University	Xian	Shanxi	China	710000
48	Xijing hospital, Air force Military Medical University	Xian	Shanxi	China	710000
49	SiChuan Cancer Hospital	Chengdu	Sichuan	China	610000
50	Suining Central Hospital	Suining	Sichuan	China	629000
51	Cancer Hospital affiliated to Xinjiang Medical University	Urumqi	Xinjiang	China	830000
52	The Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou	Zhejiang	China	310009
53	The first affiliated hospital of Zhejiang medical university	Hangzhou	Zhejiang	China
54	The Second Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang	China	325024

Sponsors and Collaborators

• Shanghai Junshi Bioscience Co., Ltd.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Shanghai Junshi Bioscience Co., Ltd.
• ClinicalTrials.gov Identifier: NCT05180734
• Other Study ID Numbers: JS001-045-III-GC
• First Posted: Jan 6, 2022
• Last Update Posted: Aug 1, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Adenocarcinoma; Esophageal Neoplasms

Study Results

No Results Posted as of Aug 1, 2022