Toripalimab Plus Pemetrexed+Platinus in Advanced Non-small-cell Lungcancer Patients Previsouly Treated EGFR-TKI

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

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 chemotherapy in 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 440 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 generation of TKI vs. 3rd generation of TKI vs. 1st or 2nd generation of TKI + 3rd generation of TKI) ; Disease stage (IIIB-C vs. IV);

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: TORIPALIMAB INJECTION(JS001 )

• Study Type: Interventional
• Enrollment (Anticipated): 440
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Caicun Zhou, prof; Phone Number: +8621-65115006-3050; Email: caicunzhoudr@163.com

Study Locations

• China
  • Shenzhen, China
    • Recruiting
    • Peking University Shenzhen Hospital
    • Contact: Zhu Li; Phone Number: 13510331612; Email: 563904040@qq.com
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Recruiting
      • Shanghai Pulmonary Hospital
      • Contact: Banyu Zhang; Phone Number: 86 021-65115006; Email: Shfkgcp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival，It's suitable for all subjects.	Approximately 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS (Progression Free Survival) by investigator	Progression free survival (PFS) evaluated by investigators according to the response evaluation criteria in solid tumors (RECIST 1.1)	Approximately 4 years
ORR (Objective Response Rate)	Objective response rate (ORR) evaluated by investigators based on RECIST1.1;	Approximately 4 years
DOR (Duration of Response)	Duration of response (DOR) evaluated by investigators and BIRC based on RECIST1.1;	Approximately 4 years
DCR (Disease of Response)	Disease control rate (DCR) evaluated by investigators based on RECIST1.1;	Approximately 4 years
TTR (Time to Response)	Time to response (TTR) evaluated by investigators based on RECIST1.1;	Approximately 4 years
Incidence of AEs/SAEs	Adverse events (AEs) study drug related; serious adverse events (SAEs)study drug related; abnormal value of Lab test according to NCI-CTCAE V5.0	Approximately 5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
pd-l1 mutation rate	To explore the correlation between pd-l1 mutation and efficacy in subjects	Approximately 4 years
immune cell classification	To explore the correlation between immune cell classification and therapeutic effect	Approximately 5 years

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Publications and helpful links

General Publications

• Jiang T, Wang P, Zhang J, Zhao Y, Zhou J, Fan Y, Shu Y, Liu X, Zhang H, He J, Gao G, Mu X, Bao Z, Xu Y, Guo R, Wang H, Deng L, Ma N, Zhang Y, Feng H, Yao S, Wu J, Chen L, Zhou C, Ren S. Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: a multicenter phase-II trial. Signal Transduct Target Ther. 2021 Oct 15;6(1):355. doi: 10.1038/s41392-021-00751-9.

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2019
• Primary Completion (Anticipated): July 17, 2023
• Study Completion (Anticipated): August 8, 2024

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: April 18, 2019
• First Posted (Actual): April 23, 2019

Study Record Updates

• Last Update Posted (Actual): December 27, 2022
• Last Update Submitted That Met QC Criteria: December 23, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: JS001-CT25-III-NSCLC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No