Phase III Study of Toripalimab Versus Placebo Plus Chemotherapy in Resectable NSCLC

NCT04158440 | Active Not Recruiting Phase 3

• 1 other identifier: JS001-029-III-NSCLC
• Study Type: interventional
• Target: 501
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Stage II-III Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (4)

• MPR rate in stage III population evaluated by BIPR

  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.

  up to 7 weeks after neoadjuvant

• EFS in stage III population evaluated by investigators

  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.

  up to 3 years

• MPR rate in stage II-III population evaluated by BIPR

  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.

  up to 7 weeks after neoadjuvant

• EFS in stage II-III population evaluated by investigators

  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: up to 3 years

Secondary Outcomes (8)

• pCR rate in stage III population evaluated by BIPR and investigators

  pCR:up to 7 weeks after neoadjuvant;

• EFS in stage III population evaluated by IRC

  EFS by IRC:up to 3 years

• Disease-free survival (DFS) in stage III evaluated by IRC and investigators

  DFS:up to 3 years

• pCR rate in stage II-III population evaluated by BIPR and investigators

  pCR:up to 7 weeks after neoadjuvant

• EFS in stage II-III population evaluated by IRC

  EFS by IRC:up to 3 years

Other Outcomes (4)

• Safety evaluation of subjects

  Safety: 90 days after the last administration

• Exploratory analysis of potential biomarkers related with the outcome

  Exploratory :withdrawal from study treatment，up to 71 weeks

• Pharmacokinetics: plasma concentration of Toripalimab in each cycle;

  Exploratory : withdrawal from study treatment，up to 71 weeks

Study Arms (2)

4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg)

EXPERIMENTAL

Participants receive totally 4 cycles of Toripalimab combined with platinum doublet chemotherapy during perioperative period ;After surgery, participants receive consolidation therapy of Toripalimab

Drug: 4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg); Biological: Toripalimab

4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo )

ACTIVE COMPARATOR

Participants receive totally 4 cycles of Placebo combined with platinum doublet chemotherapy during perioperative period ;After surgery, participants receive consolidation therapy of Placebo

Drug: 4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo )

Interventions

4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg); Biological: Toripalimab DRUG

Biological: 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: Corboplatin 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

Also known as: Cisplatin;, Carboplatin;, Pemetrexed;, Paclitaxel;, Docetaxel

4cycles(Toripalimab IV 240mg + platinum-based doublet chemotherapy)+13 cycles(Toripalimab IV 240mg)

4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo ) DRUG

Biological: Placebo 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: Corboplatin 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

Also known as: Cisplatin;, Carboplatin;, Pemetrexed;, Paclitaxel;, Docetaxel

4cycles(Placebo + platinum-based doublet chemotherapy)+13 cycles(Placebo )

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Having sufficient understanding of this study and being willing to sign the informed consent form (ICF);
• Aged 18-70 years, male or female;
• Treatment-naive, histologically confirmed resectable, stage II, IIIA, IIIB (N2) (AJCC staging system, version 8) NSCLC; cTNM stage can be confirmed through PET-CT or pathological biopsy; resectable stage II non-small cell lung cancer is defined as eligible for radical resection evaluated by a qualified thoracic surgeon; resectable stage III is defined as the resectable and potential resectable according to the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019)in which resectable includes IIIA(N0-1), partial N2 with single-station mediastinal lymph node metastasis and the short diameter of lymph node\<2 cm， partial T4 (satellite nodules in the adjacent lobe) N1 and potential resectable includes partial stage IIIA and IIIB with the short diameter of single-station N2 mediastinal lymph node\<3 cm, other potentially resectable T3 or T4 central tumor ; Any suspected lesions which could change the TNM stage, such as contralateral mediastinal lymph node, supraclavicular lymph mode, solid/sub-solid pulmonary node and non-isolated ground glass opacity (GGO), pathological confirmation is strongly recommended.
• Measurable lesions based on the response evaluation criteria in solid tumors version 1.1;
• Tumor tissue specimens available for pathological diagnosis, detection of PD-L1 expression and biomarkers prior to randomization (the tumor tissue specimens must be freshly obtained or archived samples within 3 months prior to enrollment; tumor tissue specimens must be the samples of histological category, including but not limited to the tissue punctured by core needle and hollow needle, tissue acquired by bronchoscopic clamp, surgically resected samples; the samples acquired by fine needle puncture and bronchial brushing are not acceptable);
• ECOG score 0-1;
• Good organ function:
• Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study;
• pulmonary function test being able to withstand the planned pneumonectomy evaluated by surgeons; 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.
• Women of childbearing potential must undergo serum pregnancy test within 3 days 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

You may not qualify if:

• Presence of locally advanced, unresectable or metastatic disease; unresectable includes the unresectable defined in the Chinese expert consensus on the multidisciplinary diagnosis and treatment for stage III non-small cell lung cancer (2019), including partial stage IIIA and IIIB and all the stage IIIC; N2: single station mediastinal lymph node metastasis with short diameter ≥3cm; N2: multiple station mediastinal lymph node metastasis with lymph node fusion and the short diameter of lymph node ≥2cm on CT; ALL the N3; T4: invading esophagus, heart, aorta;
• NSCLC involving superior sulcus, large cell neuroendocrine carcinoma (LCNEC), sarcomatoid tumor;
• Participants with known EGFR sensitive mutations or ALK translocation, EGFR and ALK mutation status needs to be identified for the subjects with non-squamous cell carcinoma;
• Previous treatment with systemic antitumor therapy for early NSCLC, including investigational product;
• History of (non-infectious) pneumonitis/interstitial lung disease requiring steroid treatment, or ongoing pneumonitis/interstitial lung disease requiring steroid treatment;
• Active tuberculosis;
• Active infection requiring systemic treatment;
• Subjects with any known or suspected autoimmune disorder or immunodeficiency, with the following exceptions: hypothyroidism, hormone therapy is not needed, or well controlled at physiological dose; controlled type I diabetes;
• Uncontrolled active hepatitis B (defined as positive hepatitis B surface antigen \[HBsAg\] in screening period with HBV-DNA detected higher than the upper limit of normal at the clinical laboratory of the study center); (the subjects with HBV-DNA assay \<500 IU/mL within 28 days prior to randomization who have received local standard antiviral therapy for at least 14 days and are willing to receive antiviral therapy continuously during the study can be enrolled); active hepatitis C (defined as positive hepatitis C surface antibody \[HCsAb\] in screening period and positive HCV-RNA);
• Known human immunodeficiency virus (HIV) infection (known positive HIV antibody);
• Vaccination of live vaccine within 30 days prior to the first dose. Including but not limited to the following: parotitis, rubella, measles, varicella/ herpes zoster (varicella), yellow fever, Rabies, Bacille Calmette-Guérin (BCG) and typhoid vaccine (inactivated virus vaccine allowed);
• ≥ Grade 2 peripheral neuropathy;
• Previous use of PD-1/PD-L1 agent or the drug acting on another targeted T cell receptor (e.g., CTLA-4, OX-40);
• Severe allergic reaction to other monoclonal antibodies;
• History of serious allergy to Pemetrexed, paclitaxel or docetaxel, cisplatin, carboplatin or its preventive medications;

Sponsors & Collaborators

• Shanghai Junshi Bioscience Co., Ltd.: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, China

Location

Related Publications (1)

• Lu S, Zhang W, Wu L, Wang W, Zhang P; Neotorch Investigators; Fang W, Xing W, Chen Q, Yang L, Mei J, Tan L, Sun X, Xu S, Hu X, Yu G, Yu D, Yang N, Chen Y, Shan J, Xing L, Tian H, Zhang X, Zhou M, Fang H, Wu G, Liu Y, Ye M, Cao L, Jiang J, Li X, Zhu L, Li S, Kang M, Zhong A, Chen K, Wu N, Sun Q, Ma H, Cai K, Wang C, Lin G, Zhu K, Zhang Y, Zhang X, Hu H, Zhang W, Chen J, Yang Z, Hang X, Hu J, Huang Y, Zhang Z, Zhang L, Zhang L, Liu L, Lin D, Zhang J, Chen G, Li Y, Zhu L, Wang W, Yu W, Cao D, Keegan P, Yao S. Perioperative Toripalimab Plus Chemotherapy for Patients With Resectable Non-Small Cell Lung Cancer: The Neotorch Randomized Clinical Trial. JAMA. 2024 Jan 16;331(3):201-211. doi: 10.1001/jama.2023.24735.

  PMID: 38227033 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Carboplatin; Pemetrexed; Paclitaxel; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Study Officials

• Shun Lu

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: No Masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel

Study Record Dates

• First Submitted: November 1, 2019
• First Posted: November 8, 2019
• Study Start: April 7, 2020
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: July 9, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)