Neoadjuvant Toripalimab Plus Platinum-based Doublet for Stage III Non-small Cell Lung Cancer

NCT04304248 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: SYSUCC B2019-116-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, single-arm, phase II, multi-center clinical trial. Thirty patients will be enrolled in this trial to investigate the pathological complete response rate defined as the absence of residual tumor in lung and lymph nodes treated by chemo-immunotherapy.

Conditions

Non Small Cell Lung Cancer

Keywords

Non small cell lung cancer; neoadjuvant; chemo-immunotherapy; Toripalimab

Outcome Measures

Primary Outcomes (1)

• Evaluation of the major pathologic response (MPR)

  The major pathologic response is defined as less than 10% tumor cells in the pathologically resected specimen

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 45 months

Secondary Outcomes (3)

• pathologic complete response

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 45 months

• Resectable rate

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 45 months

• Disease-free survival

  From date of enrollment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 45 months

Study Arms (1)

Neoadjuvant chemo-immunotherapy

EXPERIMENTAL

Neoadjuvant treatment (Albumin-bound paclitaxel + carboplatin + toripalimab) will start within 1-3 days from enrollment at 21-day (+/-3 days) intervals (Q3W) prior to surgery. Before surgery a tumor assessment will be done to exclude evidence of progression. Patients with radiographically stable disease or partial response may be considered for operation. Surgery: Surgery must be done within the 3rd to 4th week (+7 days) from day 21 cycle 3 of neoadjuvant treatment.

Drug: Albumin-bound paclitaxel, Carboplatin, Toripalimab

Interventions

Albumin-bound paclitaxel, Carboplatin, Toripalimab DRUG

Eligible patients will receive Toripalimab 240mg + Albumin-bound paclitaxel 260mg/m2 + Carboplatin AUC5 for 3 cycles every 21 days (+/-3 days) as neoadjuvant treatment

Neoadjuvant chemo-immunotherapy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated patients with histologically- or cytologically- documented NSCLC who present stage IIIA disease (according to 8th version of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology) and also, potentially resectable locally advanced NSCLC patients' stage IIIB with T3N2 disease according to 8th edition can be included.
• PET/CT including IV contrast (CT of diagnostic quality) will be performed at baseline (28 days +10 before randomization);
• Tumor should be EGFR wild-type or EML4-ALK negative;
• Tumor should be considered resectable before study entry by a multidisciplinary team;
• ECOG (Performance status) 0-1;
• Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to randomization.
• i. Neutrophils ≥ 1500×109/L ii. Platelets ≥ 100 x×109/L iii. Hemoglobin \> 9.0 g/dL iv. Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min v. AST/ALT ≤ 3 x ULN vi. Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL) vii. The patients need to have a forced expiratory volume (FEV1) ≥ 1.2 liters or \>40% predicted value viii. INR/APTT within normal limits;
• All patients are notified of the investigational nature of this study and signed a written informed consent in accordance with institutional and national guidelines, including the Declaration of Helsinki prior to any trial-related intervention;
• Patients aged \> 18 years;
• Women of childbearing potential, including women who had their last menstrual period in the last 2 years, must have a negative serum or urine pregnancy test within 7 days before randomization.
• All sexually active men and women of childbearing potential must use an effective contraceptive method (two barrier methods or a barrier method plus a hormonal method) during the study treatment and for a period of at least 12 months following the last administration of trial drugs;
• Patient capable of proper therapeutic compliance and accessible for correct follow-up;
• Measurable or evaluable disease (according to RECIST 1.1 criteria).

You may not qualify if:

• All patients carrying activating mutations in the TK domain of EGFR or any variety of alterations in the ALK gene.
• Patients with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
• Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
• Patients with a history of interstitial lung disease cannot be included if they have symptomatic ILD (Grade 3-4) and/or poor lung function. In case of doubt please contact trial team.
• Patients with other active malignancy requiring concurrent intervention and/or concurrent treatment with other investigational drugs or anti-cancer therapy
• Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
• Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information
• Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways
• Patients with positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
• Patients with known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Patients with history of allergy to study drug components excipients
• Women who are pregnant or in the period of breastfeeding
• Sexually active men and women of childbearing potential who are not willing to use an effective contraceptive method during the study

Sponsors & Collaborators

• Hao Long: lead

Study Sites (1)

Sun Yat sen University cancer center

Guangzhou, Guangdong, China

Location

Related Publications (1)

• Zhao ZR, Yang CP, Chen S, Yu H, Lin YB, Lin YB, Qi H, Jin JT, Lian SS, Wang YZ, You JQ, Zhai WY, Long H. Phase 2 trial of neoadjuvant toripalimab with chemotherapy for resectable stage III non-small-cell lung cancer. Oncoimmunology. 2021 Oct 25;10(1):1996000. doi: 10.1080/2162402X.2021.1996000. eCollection 2021.

  PMID: 34712513 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Albumin-Bound Paclitaxel; Carboplatin; toripalimab

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)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Coordination Complexes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: March 9, 2020
• First Posted: March 11, 2020
• Study Start: August 1, 2019
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2026
• Last Updated: May 6, 2021

Record last verified: 2021-05

Locations

CN (1)