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出境医 / 临床实验 / Toripalimab Plus Pemetrexed+Platinus in Advanced Non-small-cell Lungcancer Patients Previsouly Treated EGFR-TKI
Toripalimab Plus Pemetrexed+Platinus in Advanced Non-small-cell Lungcancer Patients Previsouly Treated EGFR-TKI
Study Description
Brief Summary:
This is a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with chemotherapyin Advanced Non-small Cell Lung Cancer (NSCLC) Participants with TKI-resistant EGFR-mutated Tumors; and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population.
About 350 subjects with advanced non-small cell lung cancer with activated EGFR mutation will be 1:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors:
The history of the previous lines of EGFR-TKI treament ( 1st or 2nd line of TKI vs. 3rd line of TKI vs. 1st or 2nd line of TKI + 3rd line of TKI) ; Disease stage (IIIB-C vs. IV);
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Non-small Cell Lung Cancer | Drug: TORIPALIMAB INJECTION(JS001 ) | Phase 3 |
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 350 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of Pemetrexed + Platinum Chemotherapy With or Without Toripalimab (JS001) in Advanced Non-small Cell Lung Cancer (NSCLC) Participants With TKI-resistant EGFR-mutated Tumors |
| Actual Study Start Date : | May 6, 2019 |
| Estimated Primary Completion Date : | July 6, 2021 |
| Estimated Study Completion Date : | May 2022 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
| Experimental: Group TORIPALIMAB combined with standard chemotherapy |
Drug: TORIPALIMAB INJECTION(JS001 )
TORIPALIMAB INJECTION(JS001 ) or Placebo, 240mg/6ml/vial, Q3W,up to 2 years of treatment.
|
| Placebo Comparator: Group Placebo combined with standard chemotherapy |
Drug: TORIPALIMAB INJECTION(JS001 )
TORIPALIMAB INJECTION(JS001 ) or Placebo, 240mg/6ml/vial, Q3W,up to 2 years of treatment.
|
Outcome Measures
Primary Outcome Measures :
- PFS (Progression Free Survival) by investigator [ Time Frame: Approximately 2 years ]Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1)
Secondary Outcome Measures :
- PFS (Progression Free Survival) by IRC (Independent Review Board） [ Time Frame: Approximately 2 years ]PFS evaluated by the Blinded Individual Review Committee (BIRC) based on RECIST1.1 criteria;
- ORR (Objective Response Rate) [ Time Frame: Approximately 2 years ]Objective response rate (ORR) evaluated by investigators and BIRC based on RECIST1.1;
- DOR (Duration of Response) [ Time Frame: Approximately 2 years ]Duration of response (DOR) evaluated by investigators and BIRC based on RECIST1.1;
- DCR (Disease of Response) [ Time Frame: Approximately 2 years ]Disease control rate (DCR) evaluated by investigators and BIRC based on RECIST1.1;
- TTR (Time to Response) [ Time Frame: Approximately 2 years ]Time to response (TTR) evaluated by investigators and BIRC based on RECIST1.1;
- OS (Overall Survival) OS OS [ Time Frame: Approximately 2 years ]Overall survival (OS);
- Incidence of AEs/SAEs [ Time Frame: Approximately 2 years ]Adverse events (AEs) study drug related; serious adverse events (SAEs)study drug related; abnormal value of Lab test according to NCI-CTCAE V5.0
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
-
Only the patients meeting all the following criteria can be eligible to participate in the trial:
- Fully informed consent and signed ICF;
- Age of 18-75 years;
- Histologically and/or cytologically confirmed advanced or recurrent stage III B-C or IV (AJCC Version 8) NSCLC with TKI-resistant EGFR-mutated tumors, which also satisfy following conditions: Without T790M mutation in exon 20 after 1st or 2nd generation EGFR-TKI (eg, gefitinib, erlotinib, icotinib, afatinib,etc.) treatment failure;If with T790M mutation in exon 20 after 1st or 2nd generation EGFR-TKI (eg, gefitinib, erlotinib, icotinib, afatinib,etc.),participants are required to have osimertinib or other 3rd generation EGFR-TKI treatment failure prior to enrollment.Participants with osimertinib treatment failure as 1st line therapy (regardless of their EGFR T790M mutation status);Previous neoadjuvant/adjuvant chemotherapy is allowed, but the time interval between the last dose of chemotherapy and recurrence/metastasis must be at least 6 months.
- With at least one measurable disease per RECIST 1.1;
- Agree to provide formalin fixed tumor specimen after EGFR-TKI treatment failure or provide fresh biopsy tissue;
- ECOG performance status of 0-1;
- Life expectancy ≥ 3 months;
- Good organ function;
- Any adverse event resulting from prior treatment, surgery, or radiotherapy must return to grade 0 or 1 according to NCI-CTCAE v5.0, except for alopecia of any grade;
- Willing and able to follow protocol visits, treatment plans, laboratory tests and other study procedures;
- Women of childbearing potential must have negative serum pregnancy test within 3 days prior to the first dose of investigational product:
Exclusion Criteria:
- Exclusion of tumor histology or cytology confirmed the presence of small cell lung cancer components, or squamous cell carcinoma components of more than 10%;
- Combined with other driver mutations with known therapeutic drug, including but not limited to: ALK rearrangement, ROS1 mutation, BRAF600E mutation, and KRAS mutation;
- Previous systematic chemotherapy for advanced NSCLC;
- Subjects with no measurable lesions;
- Subjects with cancer meningitis and spinal cord compression;
- Subjects with untreated central nervous system (CNS) tumor metastasis;
- Subjects were previously treated with an anti-PD-1, anti-PD-L1 or anti-CTLA-4 agent;
- Subjects with any active, known or suspected autoimmune disease;
- Subjects who are now participating in other clinical studies or the last dose of prior investigational drug was given in < 4 weeks (or 5 half-lives) from the first investigational product administration of this study;
- Subjects who were expected to receive any other antitumor therapy (eg, other maintenance therapy for NSCLC, radiotherapy, and/or surgical excision);
- Subjects who received major surgery within 4 weeks prior to enrollment or were not fully recovered from prior surgery;
- Subjects with other malignancies requiring concurrent treatment;
- Subjects with grade II or above myocardial ischemia or myocardial infarction, or subjects with arrhythmia with poor control;
- Subjects with uncontrolled pleural/pericardial effusion, or with ascites requiring repeated drainage;
- Subjects with uncontrolled tumor-related pain;
- Subjects with severe allergic reactions to other monoclonal antibodies and subjects with severe allergic reactions to pemetrexed, platinum or its prophylaxis;
- Subjects with psychological disorder, alcohol alcoholism, drug abuse or drug dependency
Contacts and Locations
Contacts
| Contact: Caicun Zhou, prof | +8621-65115006-3050 | caicunzhoudr@163.com |
Locations
| China | |
| Shanghai Pulmonary Hospital | Recruiting |
| Shanghai, China | |
| Peking University Shenzhen Hospital | Recruiting |
| Shenzhen, China | |
| Contact: Zhu Li 13510331612 563904040@qq.com | |
Sponsors and Collaborators
Shanghai Junshi Bioscience Co., Ltd.
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | April 18, 2019 | ||||
| First Posted Date ICMJE | April 23, 2019 | ||||
| Last Update Posted Date | August 6, 2020 | ||||
| Actual Study Start Date ICMJE | May 6, 2019 | ||||
| Estimated Primary Completion Date | July 6, 2021 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
PFS (Progression Free Survival) by investigator [ Time Frame: Approximately 2 years ] Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1)
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| Original Primary Outcome Measures ICMJE |
PFS [ Time Frame: Approximately 2 years ] Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1)
|
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| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Toripalimab Plus Pemetrexed+Platinus in Advanced Non-small-cell Lungcancer Patients Previsouly Treated EGFR-TKI | ||||
| Official Title ICMJE | A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study of Pemetrexed + Platinum Chemotherapy With or Without Toripalimab (JS001) in Advanced Non-small Cell Lung Cancer (NSCLC) Participants With TKI-resistant EGFR-mutated Tumors | ||||
| Brief Summary |
This is a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Study to evaluate the efficacy and safety of Toripalimab injection (JS001) or placebo combined with chemotherapyin Advanced Non-small Cell Lung Cancer (NSCLC) Participants with TKI-resistant EGFR-mutated Tumors; and evaluate the population with the best predictive biomarkers, i.e., positive diagnosis population. About 350 subjects with advanced non-small cell lung cancer with activated EGFR mutation will be 1:1 randomized into two groups, JS001 combined with the standard 1st-line chemotherapy will be given in the study group whereas placebo combined with standard 1st-line chemotherapy will be given in the control group. The stratification will be based on the following factors: The history of the previous lines of EGFR-TKI treament ( 1st or 2nd line of TKI vs. 3rd line of TKI vs. 1st or 2nd line of TKI + 3rd line of TKI) ; Disease stage (IIIB-C vs. IV); |
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| Detailed Description | Not Provided | ||||
| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 3 | ||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Sequential Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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| Condition ICMJE | Non-small Cell Lung Cancer | ||||
| Intervention ICMJE | Drug: TORIPALIMAB INJECTION(JS001 )
TORIPALIMAB INJECTION(JS001 ) or Placebo, 240mg/6ml/vial, Q3W,up to 2 years of treatment.
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Recruiting | ||||
| Estimated Enrollment ICMJE |
350 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Estimated Study Completion Date ICMJE | May 2022 | ||||
| Estimated Primary Completion Date | July 6, 2021 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria: - Only the patients meeting all the following criteria can be eligible to participate in the trial:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | No | ||||
| Contacts ICMJE |
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| Listed Location Countries ICMJE | China | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03924050 | ||||
| Other Study ID Numbers ICMJE | JS001-CT25-III-NSCLC | ||||
| Has Data Monitoring Committee | No | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE | Not Provided | ||||
| Responsible Party | Shanghai Junshi Bioscience Co., Ltd. | ||||
| Study Sponsor ICMJE | Shanghai Junshi Bioscience Co., Ltd. | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE | Not Provided | ||||
| PRS Account | Shanghai Junshi Bioscience Co., Ltd. | ||||
| Verification Date | April 2020 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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