Chemotherapy Plus Immunotherapy Combined With SBRT as Neoadjuvant Therapy for Patients With Resectable NSCLC

A Prospective Cohort Study of Chemotherapy Plus Immunotherapy Combined With Stereotactic Body Radiotherapy as Neoadjuvant Therapy for Patients With Resectable Non-small Cell Lung Cancer

In this study, patients with EGFR/ALK wild-type, resectable locally advanced NSCLC are expected to receive 1 cycle of chemoimmunotherapy as neoadjuvant therapy, followed by SBRT to the primary lung lesion, and chemoimmunotherapy for 2 cycles. Surgical treatment will be given within 4-6 weeks after the last cycle of chemoimmunotherapy, then immunotherapy maintenance for 1 year.

Study Overview

• Status: Recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Chemotherapy; Drug: Immunotherapy; Procedure: Radical resection of lung cancer; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yi Tang; Phone Number: 86-15068763710; Email: Beebee24@163.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310002
      • Recruiting
      • Department of Thoracic Oncology, Hangzhou Cancer Hospital
      • Contact: Lihui Fang; Phone Number: 86-571-56006035; Email: 1508590739@qq.com
      • Principal Investigator: Lucheng Zhu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically or pathologically confirmed, newly diagnosed non-small cell lung cancer patients;
2. Age ≥18 years;
3. (Eastern Cooperative Oncology Group, ECOG) (Performance Status, PS) score 0-1;
4. According to the 8th-9th edition of (American Joint Committee on Cancer, AJCC) (stage II-IIIA, for stage IIIB included T3-4N2, T4 only included tumor > 7cm);
5. Puncture or biopsy samples were tested EGFR/ALK negative;
6. Surgically or potentially resectable after discussion by multidisciplinary team (MDT);
7. Who has not received systemic antitumor therapy and has not received chest radiotherapy;
8. Evaluable lesions in the lung or mediastinum;
9. The organ function level should meet the following criteria one week before enrollment: 1) Bone marrow function: hemoglobin ≥80g/L, white blood cell count ≥4.0*10^9/L or neutrophil count ≥1.5*10^9/L, platelet count ≥100*10^9/L; 2) Liver: total serum bilirubin level ≤1.5 times the normal upper limit, when serum total bilirubin level > 1.5 times the normal upper limit, direct bilirubin level ≤ normal upper limit, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 times the normal upper limit; 3) Kidney: blood creatinine level < 1.5 times the normal upper limit or creatinine clearance ≥50ml/min, urea nitrogen ≤200mg/L; Serum albumin ≥30g/L;
10. Male/female of childbearing age agrees to use contraception during the trial period (surgical ligation or oral contraceptives/IUDs + condom contraception);
11. Sign informed consent.

Exclusion Criteria:

1. Patients with severe dysfunctions of the heart, lungs and other organs who are not suitable for surgery;
2. Patients with severe autoimmune diseases: active inflammatory bowel disease (including Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (such as Wegener's granuloma), etc;
3. Other malignancies within 5 years (excluding non-melanoma skin cancer and cervical cancer);
4. Patient with active infection, heart failure, heart attack, unstable angina pectoris or unstable arrhythmia within the last 6 months;
5. Congenital or acquired immunodeficiency disorders include human immunodeficiency virus (HIV) or a history of organ transplantation or allogeneic stem cell transplantation;
6. Patients treated with other immunological agents, chemotherapy agents, other drugs in clinical trials and long-term cortisol therapy were excluded;
7. Patients who are allergic or contraindicated to PD-1 inhibitors.

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: Treatment group

Drug: Chemotherapy; Patients with squamous cell carcinoma can choose paclitaxel + cisplatin/carboplatin and patients with nonsquamous cell carcinoma can choose pemetrexed + cisplatin/carboplatin. The chemotherapy treatment lasts 3 cycles.; Drug: Immunotherapy; Investigators choose PD-1 or PD-L1 according to drug indication and the immunotherapy lasts 3 cycles preoperatively and 1 year after surgery.; Procedure: Radical resection of lung cancer; Radical resection of lung cancer with lymph node dissection; Radiation: SBRT; SBRT for primary lung lesion 8Gy*3F after first cycle of chemoimmunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response (pCR)	Pathological complete response for surgical patients	Assessed up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major pathologic response (MPR)	No more than 10% residual viable tumour in the resected tumour (up to 24 weeks)	Assessed up to 24 weeks
1-year event-free survival (1 year EFS)	Interval between the start of neoadjuvant treatment and any progression of disease precluding surgical resection, progression of disease in the absence of surgery, progression or recurrence after surgery, or death from any cause, whichever occurred first	Assessed up to 100 months
The R0 resection rate	The proportion of patients who had complete surgical resection [R0]	Assessed up to 24 weeks
Incidence of treatment-related adverse events	The incidence of adverse events ≥ grade 3 during perioperative period	assessed up to 100 months

Collaborators and Investigators

• Sponsor: First People's Hospital of Hangzhou
• Investigators: Principal Investigator: Lucheng Zhu, MD, Hangzhou Cancer Hospital

Publications and helpful links

General Publications

• Wakelee H, Liberman M, Kato T, Tsuboi M, Lee SH, Gao S, Chen KN, Dooms C, Majem M, Eigendorff E, Martinengo GL, Bylicki O, Rodriguez-Abreu D, Chaft JE, Novello S, Yang J, Keller SM, Samkari A, Spicer JD; KEYNOTE-671 Investigators. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med. 2023 Aug 10;389(6):491-503. doi: 10.1056/NEJMoa2302983. Epub 2023 Jun 3.
• Zhang JT, Liu SY, Gao W, Liu SM, Yan HH, Ji L, Chen Y, Gong Y, Lu HL, Lin JT, Yin K, Jiang BY, Nie Q, Liao RQ, Dong S, Guan Y, Dai P, Zhang XC, Yang JJ, Tu HY, Xia X, Yi X, Zhou Q, Zhong WZ, Yang XN, Wu YL. Longitudinal Undetectable Molecular Residual Disease Defines Potentially Cured Population in Localized Non-Small Cell Lung Cancer. Cancer Discov. 2022 Jul 6;12(7):1690-1701. doi: 10.1158/2159-8290.CD-21-1486.
• Xia L, Mei J, Kang R, Deng S, Chen Y, Yang Y, Feng G, Deng Y, Gan F, Lin Y, Pu Q, Ma L, Lin F, Yuan Y, Hu Y, Guo C, Liao H, Liu C, Zhu Y, Wang W, Liu Z, Xu Y, Li K, Li C, Li Q, He J, Chen W, Zhang X, Kou Y, Wang Y, Wu Z, Che G, Chen L, Liu L. Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1). Clin Cancer Res. 2022 Aug 2;28(15):3308-3317. doi: 10.1158/1078-0432.CCR-21-3044.
• Qiu B, Guo W, Zhang F, Lv F, Ji Y, Peng Y, Chen X, Bao H, Xu Y, Shao Y, Tan F, Xue Q, Gao S, He J. Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC. Nat Commun. 2021 Nov 19;12(1):6770. doi: 10.1038/s41467-021-27022-z.
• Galluzzi L, Aryankalayil MJ, Coleman CN, Formenti SC. Emerging evidence for adapting radiotherapy to immunotherapy. Nat Rev Clin Oncol. 2023 Aug;20(8):543-557. doi: 10.1038/s41571-023-00782-x. Epub 2023 Jun 6.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2029

Study Registration Dates

• First Submitted: November 24, 2024
• First Submitted That Met QC Criteria: December 1, 2024
• First Posted (Estimated): December 5, 2024

Study Record Updates

• Last Update Posted (Estimated): December 5, 2024
• Last Update Submitted That Met QC Criteria: December 1, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; NSCLC; resectable; SBRT; locally advanced
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Immunologic Factors; Physiological Effects of Drugs; Immunomodulating Agents
• Other Study ID Numbers: HZCH-2024-003

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