MRD-guided Adjuvant Tislelizumab and Chemotherapy in Resected Stage IIA-IIIB NSCLC (Seagull)

Minimal Residual Disease (MRD)-Guided Adjuvant Tislelizumab and Chemotherapy in Resected Stage IIA-IIIB Non-small Cell Lung Cancer (NSCLC): a Randomized Controlled Phase II Study (Seagull)

Seagull is a phase Ⅱ study designed to investigate the efficacy and safety of MRD-guided adjuvant tislelizumab and chemotherapy vs adjuvant tislelizumab and chemotherapy in patients with resectable NSCLC

Study Overview

• Status: Recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: adjuvant tislelizumab and chemotherapy for MRD+ patients; Drug: adjuvant tislelizumab and chemotherapy for MRD+ patients; Drug: adjuvant chemotherapy for MRD- patients

Detailed Description

In the phase II trial, the efficacy and safety of MRD-guided adjuvant tislelizumab and chemotherapy will be compared with that of standard adjuvant tislelizumab and chemotherapy in patients with resectable NSCLC.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Feng Li, MD; Phone Number: +8615838222689; Email: LF_0604@163.com
• Study Contact Backup: Name: Yu Qi; Phone Number: +8613803892392; Email: qiyu@zzu.edu.cn

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University,
      • Contact: Feng Li, MD; Phone Number: +8615838222689; Email: LF_0604@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patient with age ≥ 18 years old, gender is not limited.
2. Histologically confirmed primary NSCLC, postoperative stage is IIA, IIB, IIIA or T3N2IIIB.
3. Receiving complete resection
4. Paraffin-embedded sections (10-15 pieces) or fresh frozen tissue are required.
5. ECOG score of 0 or 1.
6. Females of childbearing age should take appropriate contraceptive measures from screening to 3 months after discontinuation of study treatment and should not breastfeed. The pregnancy test was negative before starting dosing.
7. Male patients should use barrier contraception from screening to 3 months after discontinuation of study treatment.
8. The subjects themselves participated voluntarily and signed the informed consent in writing.

Exclusion Criteria:

1. The patient has received immune checkpoint inhibitors such as anti-PD-1, PD-L1 or CTLA-4, other immunotherapy or systemic immune modulators (including but not limited to interferon, IL-2 and TNF etc).
2. Histopathology with small cell or large cell endocrine tumor component.
3. Harboring EGFR sensitizing mutation or ALK gene translocation
4. History of other malignant tumors, except for non-melanoma skin cancer, carcinoma in situ or other solid tumors that have been effectively treated, and no evidence of any disease for >5 years after the last treatment.
5. At the start of the study treatment, there are residual toxicities of the previous treatment that are greater than CTCAE 1 and have not been alleviated, except for alopecia and grade 2 neurotoxicity caused by previous chemotherapy.
6. Any serious or uncontrolled systemic disease, including uncontrolled high blood pressure, active bleeding, active infection including hepatitis B, C, HIV, etc., which the investigator considers unsuitable to participate in the study or affect the trial program compliance.
7. History of ILD, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease
8. Insufficient bone marrow reserve or organ function.
9. History of hypersensitivity reactions to any active or inactive ingredient of tislelizumab or to drugs that are chemically similar to tislelizumab or in the same class of tislelizumab.
10. Patients who, in the judgment of the investigator, may not comply with the procedures and requirements of the study.
11. Patients who, in the investigator's judgment, have any condition that compromises patient safety or interferes with the evaluation of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MRD-guided adjuvant tislelizumab and chemotherapy; MRD+: Tislelizumab 200mg Q3W + chemotherapy 1-4 cycles and followed by Tislelizumab 200mg Q3W Up to 16 cycles or until PD or intolerable toxicity or withdrawal MRD-: Adjuvant chemotherapy and surveillance the MRD status, the patient will receive treatment for MRD+ patient when MRD detected,	Drug: adjuvant tislelizumab and chemotherapy for MRD+ patients; MRD+ patients receive adjuvant tislelizumab and chemotherapy while MRD- patients just is recommended receive adjuvant chemotherapy untill be detected MRD+ adjuvant tislelizumab and chemotherapy (cisplatin/carboplatin + paclitaxel or cisplatin/carboplatin + pemetrexed,dependent on tumor histology and at investigator's discretion); Drug: adjuvant tislelizumab and chemotherapy for MRD+ patients; patients receive adjuvant tislelizumab and chemotherapy regardless of MRD status
Active Comparator: Non MRD-guided adjuvant tislelizumab and chemotherapy; patients in non MRD-guided arm receive adjuvant tislelizumab and chemotherapy	Drug: adjuvant tislelizumab and chemotherapy for MRD+ patients; MRD+ patients receive adjuvant tislelizumab and chemotherapy while MRD- patients just is recommended receive adjuvant chemotherapy untill be detected MRD+ adjuvant tislelizumab and chemotherapy (cisplatin/carboplatin + paclitaxel or cisplatin/carboplatin + pemetrexed,dependent on tumor histology and at investigator's discretion); Drug: adjuvant tislelizumab and chemotherapy for MRD+ patients; patients receive adjuvant tislelizumab and chemotherapy regardless of MRD status; Drug: adjuvant chemotherapy for MRD- patients; MRD- patients just be recommended receive adjuvant chemotherapy untill be detected cisplatin/carboplatin + paclitaxel or cisplatin/carboplatin + pemetrexed,dependent on tumor histology and at investigator's discretion, limited to ≤4 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year PFS rate	Progression-free survival (per RECIST 1.1) is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first. Subjects who do not have disease progression will be censored at their last valid tumor assessment. PFS rate at 1 year as estimated by Kaplan-Meier method.	up to 36 months after enrollment or study close

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients changed from MRD+ to MRD- after treatment with tislelizumab for 6 months，12 months	Percentage of patients changed from MRD+ to MRD- after treatment with Tislelizumab for 9 months，12months	At the end of Cycle 8(each cycle is 21 days)、Cycle 16 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Zhengzhou University
• Collaborators: BeiGene
• Investigators: Principal Investigator: Yu Qi, the First Affiliated Hospital of Zhengzhou University

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2022
• Primary Completion (Anticipated): June 1, 2026
• Study Completion (Anticipated): June 1, 2027

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 9, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 17, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: ctDNA-MRD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: L2021-Y471

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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