ctDNA-MRD Guided Consolidation Toripalimab in Stage IB-IIIA NSCLC

NCT ID: NCT06426511

Last Updated: 2024-12-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2029-12-01

Brief Summary

This study aims to incorporate circulating tumor DNA (ctDNA)-minimal residual disease (MRD) to personalize the administration of consolidation toripalimab therapy in resected stage IB-IIIA non-small-cell lung cancer (NSCLC) after adjuvant therapy. Toripalimab is a humanized monoclonal antibody for human programmed cell death protein 1. Toripalimab was approved as a consolidation treatment after perioperative therapy in combination with chemotherapy for resectable stage III NSCLC.

Detailed Description

Most patients with stage IB-IIIA non-small cell lung cancer (NSCLC) are managed with surgery, follow by standard-of-care adjuvant platinum-based chemotherapy. However, postoperative recurrence rates remain high. Recent years, the role of checkpoint inhibitors has been proven to be effective in patients with advanced NSCLC, and even in patients with resectable NSCLC. Emerging data supports the use of consolidation checkpoint inhibitors therapy in localized NSCLC. Based on the results from Neotorch trial, consolidation toripalimab therapy led to a significant improvement in event-free survival for patients with resectable NSCLC. However, not all patients may benefit from consolidation therapy. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker for early detection of minimal residual disease (MRD) in cancer surveillance. There is a critical need to identify MRD after curative therapies to determine which patients may benefit from consolidation toripalimab therapy. The aim of this study is to explore whether observation follow-up for patients with negative ctDNA after adjuvant therapy has a non-inferior prognosis for patients with positive ctDNA and received consolidation toripalimab therapy. This study aims to incorporate ctDNA-MRD to personalize the administration of consolidation toripalimab therapy for completely resected stage IB-IIIA NSCLC (without EGFR or ALK alterations for nonsquamous NSCLC).

Conditions

Lung Cancer, Nonsmall Cell

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Observation for undetectable ctDNA after adjuvant therapy

Observation follow-up for patients with undetectable ctDNA after 4 cycles of adjuvant chemotherapy plus toripalimab.

Group Type: EXPERIMENTAL

Toripalimab+Chemotherapy

Intervention Type: DRUG

After surgical resection, patients received 4 cycle of toripalimab (240 mg) in combination with platinum-based adjuvant treatment. Administration of standard postoperative adjuvant chemotherapy for stage IB disease was not mandatory; decisions about whether patients with IB disease would receive adjuvant chemotherapy were made by the physicians.

Consolidation toripalimab for detectable ctDNA after adjuvant therapy

Consolidation toripalimab therapy for up to 13 cycles for patients with detectable ctDNA after 4 cycles of adjuvant chemotherapy plus toripalimab.

Group Type: ACTIVE_COMPARATOR

Toripalimab+Chemotherapy followed by consolidation toripalimab

Intervention Type: DRUG

After surgical resection, patients received 4 cycle of toripalimab (240 mg) in combination with platinum-based adjuvant treatment, and then maintenance treatment with single-agent toripalimab (240 mg) once every 3 weeks for up to 13 cycles.

Administration of standard postoperative adjuvant chemotherapy for stage IB disease was not mandatory; decisions about whether patients with IB disease would receive adjuvant chemotherapy were made by the physicians.

Interventions

Toripalimab+Chemotherapy

After surgical resection, patients received 4 cycle of toripalimab (240 mg) in combination with platinum-based adjuvant treatment. Administration of standard postoperative adjuvant chemotherapy for stage IB disease was not mandatory; decisions about whether patients with IB disease would receive adjuvant chemotherapy were made by the physicians.

Intervention Type: DRUG

Toripalimab+Chemotherapy followed by consolidation toripalimab

After surgical resection, patients received 4 cycle of toripalimab (240 mg) in combination with platinum-based adjuvant treatment, and then maintenance treatment with single-agent toripalimab (240 mg) once every 3 weeks for up to 13 cycles.

Administration of standard postoperative adjuvant chemotherapy for stage IB disease was not mandatory; decisions about whether patients with IB disease would receive adjuvant chemotherapy were made by the physicians.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects must have undergone complete surgical resection (R0) of their stage IB , II and select IIIA NSCLC according to the AJCC 8th edition staging;
• Squamous or non-squamous NSCLC histology;
• Subjects should be without EGFR or ALK alterations for nonsquamous NSCLC;
• Male and female, aged 18-75 years;
• Surgery for lung cancer must be completed ≤ 60 days prior to study treatment;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level);
• Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN;
• Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min;
• Female subjects should not be pregnant or breast-feeding;
• Written informed consent provided. Being willing and able to comply with the visits, treatment plan, laboratory examinations and other study procedures scheduled in the study.

Exclusion Criteria

• Not R0 resection, or metastatic disease.
• Subjects with known EGFR sensitive mutations or ALK translocation, EGFR and ALK mutation status needs to be identified for the subjects with non-squamous NSCLC;
• Previous treatment with systemic antitumor therapy for NSCLC;
• Severe allergic reaction to other monoclonal antibodies;
• 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 in screening period with HBV-DNA detected higher than the upper limit of normal at the clinical laboratory of the study center); active hepatitis C (defined as positive hepatitis C surface antibody in screening period and positive HCV-RNA);
• Vaccination of live vaccine within 30 days prior to the first dose;
• Evidence of clinically active interstitial lung disease;
• Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS);
• Inability to comply with protocol or study procedures;
• Any unstable systemic disease (including active infection, active tuberculosis uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease);
• A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study and may confuse the study results;
• History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
• Women who are pregnant or nursing.
• Ingredients mixed with small cell lung cancer patients.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Si-Yu Wang

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Si-Yu Wang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Si-Yu Wang, MD

Role: CONTACT

Phone: +86 20 87343439

Email: wangsy@sysucc.org.cn

Facility Contacts

Si-Yu Wang, Doctor

Role: primary

Other Identifiers

GASTO10112

Identifier Type: -

Identifier Source: org_study_id