A Study of Toripalimab or Placebo Plus Chemotherapy as Treatment in Early Stage NSCLC

Overview

This is a randomized, double-blind, placebo-controlled, multi-center, phase III trial to evaluate the efficacy and safety of Toripalimab injection (JS001) combined with platinum-based doublet chemotherapy versus placebo combined with platinum-based doublet chemotherapy in resectable stage IIIA NSCLC.

Subjects meet all the inclusion and exclusion criteria will be paralleled assigned according to the stratification factors as below:

- Pathological type: squamous cell carcinoma vs. non-squamous cell carcinoma

- PD-L1 status: PD-L1 expression ≥1% vs. PD-L1<1% or not evaluable

- Planned surgical operation: pneumonectomy vs. lobectomy Neoadjuvant therapy should be started within 3 days after randomization. Toripalimab IV 240mg Q3W will be given combined with platinum-based doublet chemotherapy for three cycles in the neoadjuvant setting in the experimental group; Every 3 weeks of treatment is regarded as one cycle, in which combined therapy is given in the first day of every cycle. Placebo combined with platinum-based doublet chemotherapy will be given for three cycles in the control group instead.

All the subjects will receive preoperative radiological and surgical evaluation 3-5 weeks after neoadjuvant therapy.

All the qualified subjects will receive radical excision based on the surgical operation criteria of the World Association for Lung Cancer Research within 4-6 weeks after neoadjuvant therapy. Pathologic staging based on AJCC Cancer Staging Manual (version 8) of the whole specimens will be performed by the local pathologist. And then all the specimens will be sent to the BIPR for further evaluation. All the subjects accept the radical operation will receive one cycle of postoperative neoadjuvant therapy, i.e., Toripalimab IV 240mg / placebo + platinum-based doublet chemotherapy, 30 days after the operation. In case of no indication for radiotherapy, it will proceed to consolidation treatment period three weeks later; if indicated for radiotherapy, it will proceed to consolidation treatment period 30 days after the radiotherapy. In the consolidation treatment setting, JS001 is given by IV 240mg in each cycle of every 3 weeks for a total of 13 cycles i in the experimental group; placebo is given by IV 240mg in each cycle of every 3 weeks for a total of 13 cycles in the control group. Adverse events (AE) will be monitored throughout the study, and the seriousness will be graded to the guideline in national cancer institute (NCI) common terminology criteria for adverse events (CTCAE) version 5.0 or above. The safety will be followed up in the subjects who have received treatment and discontinued the drug prematurely. All the subjects will be followed up for overall survival, until death, withdrawal of informed consent or end of study.

Full Title of Study: “A Randomized,Double-blinded, Multi-center Phase III Study of Toripalimab or Placebo Plus Chemotherapy as Treatment in Early Stage Non-Small Cell Lung Cancer”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: May 31, 2022

Interventions

  • Drug: Toripalimab + platinum-based doublet chemotherapy
    • Toripalimab 240 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1;Drug: Cisplatin 75 mg/m^2 by IV infusion Q3W, given on cycle day 1;Drug: Carboplatin AUC 5 by IV infusion Q3W, given on cycle day 1;Drug: Pemetrexed 500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.Drug:Paclitaxel 175 mg/m^2 by IV infusion Q3W;Drug:Docetaxel 60-75 mg/m^2 by IV infusion Q3W
  • Drug: Placebo + platinum-based doublet chemotherapy
    • placebo 240 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1;Drug: Cisplatin 75 mg/m^2 by IV infusion Q3W, given on cycle day 1;Drug: Carboplatin AUC 5 by IV infusion Q3W, given on cycle day 1;Drug: Pemetrexed 500 mg/m^2 by IV infusion Q3W, given on cycle day 1. Given only to participants with nonsquamous NSCLC.Drug:Paclitaxel 175 mg/m^2 by IV infusion Q3W;Drug:Docetaxel 60-75 mg/m^2 by IV infusion Q3W

Arms, Groups and Cohorts

  • Active Comparator: Toripalimab + platinum-based doublet chemotherapy
    • Participants receive totally 4 cycles of Toripalimab combined with platinum doublet chemotherapy during perioperative period ;After surgery, participants receive consolidation therapy of Toripalimab
  • Placebo Comparator: Placebo + platinum-based doublet chemotherapy
    • Participants receive totally 4 cycles of placebo combined with platinum doublet chemotherapy during perioperative period ;After surgery, participants receive consolidation therapy of placebo

Clinical Trial Outcome Measures

Primary Measures

  • Major Pathological Response by BIPR
    • Time Frame: MPR:up to 7 weeks after neoadjuvant
    • Major Pathological Response (mPR) Rate.mPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes in neoadjuvant therapy
  • Event Free Survival by investigator
    • Time Frame: EFS:up to 3 years
    • Event Free Survival (EFS):EFS is defined as the time from randomization until radiographic disease progression, local progression precluding surgery, inability to resect the tumor, local or distant recurrence, or death due to any cause. EFS determined either by biopsy assessed by blinded central pathologist or by imaging using RECIST 1.1 assessed by BICR.

Participating in This Clinical Trial

Inclusion Criteria

1. Having sufficient understanding of this study and being willing to sign the informed consent form (ICF);

2. Age 18-70 years, male or female;

3. Treatment-naive, histologically confirmed, resectable stage IIIA (AJCC staging system version 8) NSCLC;

4. Measurable lesion based on the response evaluation criteria in solid tumors version 1.1;

5. Being will to provide specimens or related pathological report for the biomarkers evaluation prior to the randomization.

6. ECOG score 0-1;

7. Good organ function:

8. Being willing and able to comply with visits, treatment plan, laboratory examinations and other study procedures scheduled .

9. Total lung capacity is able to withstand the planned pneumonectomy evaluated by surgeons;

10. Women of childbearing potential must undergo serum pregnancy test within 3 hours prior to the first dose and the result must be negative. Female subjects of childbearing potential and male subjects whose partners are women of childbearing potential must agree to use highly effective contraceptive methods during the study period and within 180 days after the last dose of study drug.

Exclusion Criteria

1. Locally advanced, unresectable or metastatic disease.

2. NSCLC involving superior sulcus, large cell neuroendocrine carcinoma (LCNEC), sarcomatoid tumor.

3. Participants with known EGFR mutation or ALKfusion .

4. Early NSCLC previously treated with systemic antitumor therapy, including investigational product.

5. History or current evidence of any disease, therapy or abnormal laboratory examination that may confound the study results, interfere with subject's participation in the whole study or not meet the best interest of subject's participation in the study, as judged by investigators.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Shanghai Junshi Bioscience Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • zhang xun, 86-18613210517, xun_zhang@junshipharma.com

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