A Single-arm Exploratory Study of Neoadjuvant Therapy

Neoadjuvant Tislelizumab and Platinum-Based Doublet Chemotherapy in Stage II-IIIB EGFR-Mutated Lung Adenocarcinoma With PD-L1 Positive Expression -- A Phase II Study (DuoVitality)"

Neoadjuvant EGFR TKI therapy targeting EGFR mutation has some problems failure to fulfill clinical requirements such as low MPR rate, tissue fibrosis and other major surgical impacts and unmet clinical needs.This study hypothesized that Tisleizumab combined with chemotherapy in the neoadjuvant treatment of stage II-IIIA non-squamous NSCLC with EGFR-mutant PD-L1 expression ≥1% could significantly improve the pathological response rate after neoadjuvant therapy, improve the surgical complete resection rate, reduce perioperative complications and do not increase the surgical difficulty.In this study, biomarker analysis is going to explore the possible direction of neoadjuvant therapy population screening, and to explore a possible method for the efficacy and safety of neoadjuvant immunotherapy in clinical stage II-IIIA non-squamous non-small cell lung cancer with EGFR mutation and expression of PD-L1.

Study Overview

• Status: Recruiting
• Conditions: Lung Adenocarcinoma
• Intervention / Treatment: Drug: Tislelizumab; Drug: pemetrexed; Drug: cis-platemum; Drug: or carboplatin

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Henry liang, Dr; Phone Number: 15625064712; Email: hengrui_liang@163.com

Study Locations

• China
  • Please Select
    • Guangzhou, Please Select, China, 510000
      • Recruiting
      • First Affiliated Hospital, Guangzhou Medical University
      • Contact: hengrui liang; Phone Number: 15625064712; Email: hengrui_liang@163.com
      • Principal Investigator: Jun Liu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Volunteer to participate in clinical research;Fully understand and be Informed of the study and sign the Informed Consent Form (ICF);Willing to follow and able to complete all test procedures;
2. Age 18-75 (boundary value included), no gender limitation;
3. Histologically proven stage II-IIIB Lung Adenocarcinoma (as defined by the American Joint Commission on Cancer, 8th Edition);
4. EGFR gene mutation positive (can be tested by tissue or blood samples);
5. PD-L1 ≥ 1%
6. ECOG PS score 0-1 (including boundary value);
7. Cardiopulmonary function is good, and the requirements for surgical resection for radical treatment are confirmed;
8. Meet the conditions for receiving platinum containing two-drug chemotherapy;
9. The expected survival time is ≥3 months, and feasible surgery is planned;

Exclusion Criteria:

1. Any previous treatment for current lung cancer, including systemic therapy or radiotherapy;
2. there are locally advanced unresectable diseases (regardless of disease stage) and metastatic diseases (stage IV).
3. A history of interstitial lung disease, non-infectious pneumonia or uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, etc.Patients with any severe and/or uncontrolled disease or symptom

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant ICI combined with chemotherory; intravenous injection :Tislelizumab + pemetrexed + platinum Q3W 2-4 cycles	Drug: Tislelizumab; 200 mg ,intravenous injection ,Q3W 2-4 cycles; Drug: pemetrexed; 500 mg/m2,intravenous injection ,Q3W 2-4 cycles; Drug: cis-platemum; 60-75mg/m2 ,intravenous injection ,Q3W 2-4 cycles; Drug: or carboplatin; AUC(4-5) ,intravenous injection ,Q3W 2-4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response rate (MPR) （proportion of patients with no more than 10% remaining live tumor cells in the resected primary tumor and in all resected lymph nodes）	MPR of surgical specimens from patients who were operable after neoadjuvant therapy was evaluated	15-18 weeks after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR: Proportion of patients who achieved complete response (CR) or partial response (PR) among all randomized patients with measurable disease at baseline assessed according to RECIST version 1.1	To evaluate objective response rate (ORR) in neoadjuvant treatment	6-12weeks after enrollment
pCR: proportion of patients with no residual tumor in resected primary tumor and lymph nodes	pCR of surgical specimens from patients who were operable after neoadjuvant therapy was evaluated	15-18 weeks after enrollment
Descending rate of lymph nodes	Proportion of patients whose pathologic lymph node stage was reduced to N1/N0 by baseline radiographic assessment of N2 or N1	15-18 weeks after enrollment
Number of Participants with Adverse Events	To evaluate the safety profile(Number of Participants with Adverse Events)	through study completion, an average of 35weeks
The time of surgery delay	evaluate the interval time from the completation of last neoadjuvant therapy to surgery	4-6weeks after completation of the last neoadjuvant therapy
minimally invasive surgery rate	explore different surgery manner rate after neoadjuvant	4-6weeks after completation of the last neoadjuvant therapy

Collaborators and Investigators

• Sponsor: Jun Liu
• Investigators: Principal Investigator: Jun liu, Professor, 1First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China

Publications and helpful links

General Publications

• Chansky K, Detterbeck FC, Nicholson AG, Rusch VW, Vallieres E, Groome P, Kennedy C, Krasnik M, Peake M, Shemanski L, Bolejack V, Crowley JJ, Asamura H, Rami-Porta R; IASLC Staging and Prognostic Factors Committee, Advisory Boards, and Participating Institutions. The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer. J Thorac Oncol. 2017 Jul;12(7):1109-1121. doi: 10.1016/j.jtho.2017.04.011. Epub 2017 Apr 28.
• Wozniak AJ, Gadgeel SM. Adjuvant therapy for resected non-small cell lung cancer. Ther Adv Med Oncol. 2009 Sep;1(2):109-18. doi: 10.1177/1758834009338634.
• Rosell R, Lopez-Cabrerizo MP, Astudillo J. Preoperative chemotherapy for stage IIIA non-small cell lung cancer. Curr Opin Oncol. 1997 Mar;9(2):149-55. doi: 10.1097/00001622-199703000-00008.
• Zhong WZ, Chen KN, Chen C, Gu CD, Wang J, Yang XN, Mao WM, Wang Q, Qiao GB, Cheng Y, Xu L, Wang CL, Chen MW, Kang X, Yan W, Yan HH, Liao RQ, Yang JJ, Zhang XC, Zhou Q, Wu YL. Erlotinib Versus Gemcitabine Plus Cisplatin as Neoadjuvant Treatment of Stage IIIA-N2 EGFR-Mutant Non-Small-Cell Lung Cancer (EMERGING-CTONG 1103): A Randomized Phase II Study. J Clin Oncol. 2019 Sep 1;37(25):2235-2245. doi: 10.1200/JCO.19.00075. Epub 2019 Jun 13.
• NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet. 2014 May 3;383(9928):1561-71. doi: 10.1016/S0140-6736(13)62159-5. Epub 2014 Feb 25.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Estimated): June 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: September 2, 2022
• First Posted (Actual): September 6, 2022

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; Neoadjuvant immunotherapy; EGFR mutation and PD-L1≥1%; Resectable II-IIIB
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenocarcinoma; Adenocarcinoma of Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Folic Acid Antagonists; Carboplatin; Pemetrexed; Tislelizumab
• Other Study ID Numbers: Tislelizumab-Neoadjuvant

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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