A Study of RC48-ADC in Local Advanced or Metastatic Gastric Cancer With the HER2-Overexpression

Sponsor

RemeGen Co., Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04714190

Collaborator

(none)

351

Enrollment

Locations

Arms

45.3

Anticipated Duration (Months)

6.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase III, randomized, multicenter, open-label clinical trial designed to compare RC48-ADC to physician choice standard treatment in participants with human epidermal growth factor receptor 2 (HER2)-overexpression locally advanced or metastatic gastric cancer.

Condition or Disease	Intervention/Treatment	Phase
Gastric Cancer HER2 Overexpressing Gastric Carcinoma	Drug: RC48-ADC Drug: Paclitaxel injection Drug: Irinotecan Hydrochloride Injection Drug: Apatinib Mesylate Tablets	Phase 3

Detailed Description

This study is a phase III multi-center, randomized, open-label, parallel control study to evaluate the efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody-Monomethyl auristatin E (MMAE) conjugate for the treatment of HER2-overexpression locally advanced or metastatic gastric cancer. The HER2-overexpression is defined as: the HER2 IHC 3+ or 2+, regardless of FISH status.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

351 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Randomized, Controlled, Multicenter Phase III Clinical Study Evaluating the Efficacy and Safety of RC48-ADC for the Treatment of Locally Advanced or Metastatic Gastric Cancer With HER2-overexpression

Actual Study Start Date :

Mar 24, 2021

Anticipated Primary Completion Date :

Jul 1, 2022

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: RC48-ADC Participants will receive RC48-ADC every 2 weeks (Q2W) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).	Drug: RC48-ADC 2.5 mg/kg IV every 2 weeks Other Names: Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection
Active Comparator: Physician's Choice Participants will receive physician choosed chemotherapy from the following options: Paclitaxel Injection or Irinotecan Hydrochloride Injection or Apatinib Mesylate Tablets oral.	Drug: Paclitaxel injection Administered according to label, as one option for Physician's Choice (determined before randomization) Other Names: Taxol Drug: Irinotecan Hydrochloride Injection Administered according to label, as one option for Physician's Choice (determined before randomization) Other Names: CAMPTO Drug: Apatinib Mesylate Tablets Administered according to label, as one option for Physician's Choice (determined before randomization) Other Names: Aitan

Arm

Intervention/Treatment

Experimental: RC48-ADC

Participants will receive RC48-ADC every 2 weeks (Q2W) until investigator assessed loss of clinical benefit, unacceptable toxicity, investigator or participant decision to withdraw from therapy, or death (whichever occurs first).

Drug: RC48-ADC

2.5 mg/kg IV every 2 weeks

Other Names:

Recombinant Humanized anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection

Active Comparator: Physician's Choice

Participants will receive physician choosed chemotherapy from the following options: Paclitaxel Injection or Irinotecan Hydrochloride Injection or Apatinib Mesylate Tablets oral.

Drug: Paclitaxel injection

Administered according to label, as one option for Physician's Choice (determined before randomization)

Other Names:

Taxol

Drug: Irinotecan Hydrochloride Injection

Administered according to label, as one option for Physician's Choice (determined before randomization)

Other Names:

CAMPTO

Drug: Apatinib Mesylate Tablets

Administered according to label, as one option for Physician's Choice (determined before randomization)

Other Names:

Aitan

Outcome Measures

Primary Outcome Measures

Overall survival (OS) [within approximately 3 years]
Overall survival (OS) refers to the time from the date of randomization to the date of death of the subject.

Secondary Outcome Measures

Progression-free survival (PFS), evaluated by the investigator [within approximately 3 years]
Progression-free survival (PFS) refers to the time from the date of randomization to the first researcher's evaluation of disease progression or death (calculated by the event that occurred first). The disease progression will be evaluated by the researchers according to the RECIST 1.1 standard.
Objective remission rate (ORR) [within approximately 3 years]
The objective response rate will be mainly analyzed by the independent efficacy evaluation committee according to the RECIST 1.1 standard tumor evaluation (the evaluation by the investigator will also be performed).
Duration of relief (DOR) [within approximately 3 years]
DOR is defined as the time from the first documented objective response (CR or PR) to the first documented disease progression or death
Disease control rate (DCR) [within approximately 3 years]
Disease control rate (DCR) is defined as cases where objective remission (assessed as complete remission or partial remission according to RECIST 1.1 standard) or stable disease during the study.
Tumor progression time (TTP) [within approximately 3 years]
Time to disease progression (TTP) refers to the time from the random date to the first disease progression (calculated by the event that occurred first). Disease progression will be evaluated by the investigator according to the RECIST 1.1 standard (investigator and Independent Review Committee(IRC) evaluation).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Voluntary agreement to provide written informed consent.
Male or female, Age ≥ 18 years.
Predicted survival ≥ 12 weeks.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically.Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception.
Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
Adequate organ function.
All subjects must have inoperable, advanced or metastatic gastric or or gastroesophageal adenocarcinoma
Have had progression or intolerance following receipt of at least two systemic chemotherapy for advanced or metastatic disease.
The HER2 IHC test result is IHC 2+ or IHC 3+, the subject's previous test results (confirmed by the investigator) or the research center's test results are acceptable; the subject can provide the Specimen of primary or metastatic tumor for HER2 review/judgment.
HER2 classic positive (definition: IHC3+ or IHC2+FISH+) and patients who have previously failed standard treatment
According to the RECIST 1.1 standard, there is at least one measurable lesion.

Exclusion Criteria:

Known hypersensitivity to Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection.
History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment.
History of major surgery within 4 weeks of planned start of trial treatment.
Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Cancer Hospital	Beijing	Beijing	China	100142
2	Affiliated Hospital of Hebei University	Baoding		China
3	China-Japan Friendship Hospital	Beijing		China
4	Luhe Hospital Affiliated to Capital Medical University	Beijing		China
5	Peking University People's Hospital	Beijing		China
6	Jilin Provincial Tumor Hospital	Changchun		China
7	Xiangya Hospital of Central South University	Changsha		China
8	Affiliated Hospital of Chengde Medical College	Chengde		China
9	Three Gorges Hospital Affiliated to Chongqing University	Chongqing		China
10	Fujian Cancer Hospital	Fuzhou		China
11	Guangdong Provincial People's Hospital	Guangzhou		China
12	Southern Hospital of Southern Medical University	Guangzhou		China
13	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou		China
14	The Sixth Affiliated Hospital of Sun Yat-sen University	Guangzhou		China
15	First Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou		China
16	Second Affiliated Hospital of Zhejiang University School of Medicine	Hangzhou		China
17	Zhejiang Cancer Hospital	Hangzhou		China
18	The Affiliated Tumor Hospital of Harbin Medical University	Harbin		China
19	Anhui Cancer Hospital	Hefei		China
20	Anhui Provincial Hospital	Hefei		China
21	Jinan Central Hospital	Jinan		China
22	Shandong Cancer Hospital	Jinan		China
23	Affiliated Hospital of Jining Medical College	Jining		China
24	The First People's Hospital of Jining City	Jining		China
25	Lanzhou University Second Hospital	Lanzhou		China
26	Linyi Tumor Hospital	Linyi		China
27	Drum Tower Hospital Affiliated to Nanjing University School of Medicine	Nanjing		China
28	Jiangsu Cancer Hospital	Nanjing		China
29	The First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People's Hospital)	Nanjing		China
30	Qingdao University Hospital	Qingdao		China
31	Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine	Shanghai		China
32	Shanghai Changhai Hospital	Shanghai		China
33	Zhongshan Hospital Affiliated to Fudan University	Shanghai		China
34	Cancer Hospital Affiliated to Shantou University Medical College	Shantou		China
35	Liaoning Cancer Hospital	Shenyang		China
36	Shenzhen People's Hospital	Shenzhen		China
37	The First Affiliated Hospital of Soochow University	Suzhou		China
38	Shanxi Cancer Hospital	Taiyuan		China
39	Tianjin Cancer Hospital	Tianjin		China
40	Weifang People's Hospital	Weifang		China
41	Weihai Municipal Hospital	Weihai		China
42	Huazhong University of Science Tongji Hospital, Tongji Medical College	Wuhan		China
43	The First Affiliated Hospital of Xi'an Jiaotong University	Xi'an		China
44	The First Affiliated Hospital of Xiamen University	Xiamen		China
45	Affiliated Hospital of Qinghai University	Xining		China
46	Qinghai Provincial People's Hospital	Xining		China
47	The First Affiliated Hospital of Xinxiang Medical College	Xinxiang		China
48	Affiliated Hospital of Xuzhou Medical University	Xuzhou		China
49	Xuzhou Central Hospital	Xuzhou		China
50	Subei People's Hospital of Jiangsu Province	Yangzhou		China
51	Yantai Yuhuangding Hospital	Yantai		China
52	Henan Cancer Hospital	Zhengzhou		China