## Protocol Section
### Identification Module
**NCT ID:** NCT06426511

**Acronym:** CONTINUE

**Brief Title:** ctDNA-MRD Guided Consolidation Toripalimab in Stage IB-IIIA NSCLC

**Official Title:** Consolidation Toripalimab Therapy Guided by Circulating Tumor DNA (ctDNA)-Minimal Residual Disease (MRD) for Completely Resected Stage IB-IIIA Non-small-cell Lung Cancer (Without EGFR or ALK Alterations for Nonsquamous Lung Cancer)

#### Organization Study ID Info
**ID:** GASTO10112
#### Organization
**Class:** OTHER
**Full Name:** Sun Yat-sen University
### Status Module
#### Completion Date
**Date:** 2029-07-01

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-23

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-17

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-07-01

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-07-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-23
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-17
**Study First Submit QC Date:** 2024-05-17
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Sun Yat-sen University

#### Responsible Party

**Investigator Affiliation:** Sun Yat-sen University

**Investigator Full Name:** Si-Yu Wang

**Investigator Title:** Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**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 Module

**Conditions:**

- Lung Cancer, Nonsmall Cell

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Incorporate ctDNA-MRD to personalize the administration of consolidation toripalimab therapy for completely resected stage IB-IIIA NSCLC

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 80

**Type:** ESTIMATED

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

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

**Intervention Names:**

- Drug: Toripalimab+Chemotherapy

**Label:** Observation for undetectable ctDNA after adjuvant therapy

**Type:** EXPERIMENTAL

#### Arm Group 2

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

**Intervention Names:**

- Drug: Toripalimab+Chemotherapy followed by consolidation toripalimab

**Label:** Consolidation toripalimab for detectable ctDNA after adjuvant therapy

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Observation for undetectable ctDNA after adjuvant therapy

**Description:** 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.

**Name:** Toripalimab+Chemotherapy

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Consolidation toripalimab for detectable ctDNA after adjuvant therapy

**Description:** 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.

**Name:** Toripalimab+Chemotherapy followed by consolidation toripalimab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Determine if ctDNA-MRD guided consolidation toripalimab has a non-inferior 2-year DFS to direct 13 cycles of consolidation toripalimab therapy.

2-year DFS was defined as the proportion of patients who were disease free at 2 years.

**Measure:** The 2-year DFS rate of ctDNA-MRD guided consolidation toripalimab

**Time Frame:** Baseline to 24 months

#### Secondary Outcomes

**Description:** Determine if ctDNA-MRD guided consolidation toripalimab has a non-inferior 2-year OS to direct 13 cycles of consolidation toripalimab therapy.

2-year OS was defined as the proportion of patients who were alive at 2 years.

**Measure:** The 2-year OS rate of ctDNA-MRD guided consolidation toripalimab

**Time Frame:** Baseline to 24 months

**Description:** Estimate the 2-year DFS in patients with persistently detectable ctDNA after receiving ≥6 months of consolidation toripalimab.

**Measure:** The 2-year DFS in patients with persistently detectable ctDNA

**Time Frame:** Baseline to 24 months

**Description:** Percentage of patients with undetectable ctDNA after consolidation toripalimab of 13 cycles.

**Measure:** Percentage of patients with undetectable ctDNA after consolidation toripalimab.

**Time Frame:** Baseline to 15 months

**Description:** Percentage of patients with detectable ctDNA after 4 cycles of adjuvant chemotherapy plus toripalimab.

**Measure:** Percentage of patients with detectable ctDNA after adjuvant chemotherapy plus toripalimab.

**Time Frame:** Baseline to 3 months

**Description:** Adverse Events were monitored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.

**Measure:** Adverse Events

**Time Frame:** Baseline to 36 months

### Eligibility Module

**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.

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** wangsy@sysucc.org.cn

**Name:** Si-Yu Wang, MD

**Phone:** +86 20 87343439

**Role:** CONTACT

#### Overall Officials

**Official 1:**

**Affiliation:** Sun Yat-sen University

**Name:** Si-Yu Wang, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Info Types:**

- STUDY_PROTOCOL

- SAP

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000012142

- Term: Respiratory Tract Neoplasms

- ID: D000013899

- Term: Thoracic Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000008171

- Term: Lung Diseases

- ID: D000012140

- Term: Respiratory Tract Diseases

- ID: D000002283

- Term: Carcinoma, Bronchogenic

- ID: D000001984

- Term: Bronchial Neoplasms

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC08

- Name: Respiratory Tract (Lung and Bronchial) Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M5546

- Name: Carcinoma, Non-Small-Cell Lung

- Relevance: HIGH

- As Found: Lung Cancer, Nonsmall Cell

- ID: M11172

- Name: Lung Neoplasms

- Relevance: HIGH

- As Found: Lung Cancer

- ID: M20497

- Name: Neoplasm, Residual

- Relevance: LOW

- As Found: Unknown

- ID: M5534

- Name: Carcinoma

- Relevance: LOW

- As Found: Unknown

- ID: M14979

- Name: Respiratory Tract Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M16658

- Name: Thoracic Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M11168

- Name: Lung Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14977

- Name: Respiratory Tract Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5540

- Name: Carcinoma, Bronchogenic

- Relevance: LOW

- As Found: Unknown

- ID: M5260

- Name: Bronchial Neoplasms

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008175

- Term: Lung Neoplasms

- ID: D000002289

- Term: Carcinoma, Non-Small-Cell Lung

### Misc Info Module

- Version Holder: 2024-05-31
