Neoadjuvant Toripalimab for Clinically Stage II-IIIB Resectable Non-small Cell Lung Cancer with EGFR Mutation and PD-L1 Positive Expression

NCT06269211 | Recruiting Phase 2

• 1 other identifier: RTS-019
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

The study is a prospective, open label, multicenter, single arm Phase II clinical trial, aiming to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC patients. This study will provide valuable information for further clinical trials of neoadjuvant Toripalimab and other immune checkpoint inhibitors in NSCLC patients with EGFR mutations and PD-L1 positive expression.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Major Pathological Response (MPR)

  Defined as the incidence rate in postoperative pathology where the percentage of surviving tumor cells in the tumor bed is ≤ 10%, regardless of the presence or absence of live tumor cells in the lymph nodes.

  MPR will be assessed within 2 weeks after surgery

Secondary Outcomes (6)

• Pathological Complete Response (pCR)

  pCR will be assessed within 2 weeks after surgery

• Objective Response Rate (ORR)

  Tumor response will be evaluated within 30 days after last dose of neoadjuvant treatment

• 2-year Event Free Survival (EFS)

  2 years after the date of initiation of neoadjuvant treatment

• 2-year Overall Survival (OS)

  2 years after the date of initiation of neoadjuvant treatment

• Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)

  From date of neoadjuvant treatment until surgery was applied during study period or up to at least 90 days after last dose.

Study Arms (1)

Toripalimab

EXPERIMENTAL

Neoadjuvant Toripalimab 240 mg IV on cycle 1 day 1 (C1D1), C2D1 and C3D1 before radical surgery for lung cancer. The participants will attend follow-up visits based on molecular residual disease (MRD) and receive adjuvant treatment including EGFR-TKI or chemotherapy if recommended.

Drug: Toripalimab

Interventions

Toripalimab DRUG

240mg IV, Q3W

Toripalimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women aged ≥ 18 years old.
• Baseline tumor tissues have to be obtained through biopsy (percutaneous or transbronchial) or surgery at study center.
• Histologically confirmed diagnosis of primary non-small lung cancer on non-squamous histology.
• Pre-treatment stage as clinical II-IIIB (AJCC/UICC 8th Edition) (stage IIIB excludes N3 disease); curative resectability has to be explicitly verified by the experienced surgical investigator.
• Confirmation by the central laboratory that the tumor harbors EGFR mutations either sensitive mutations, uncommon mutations or complex mutations.
• Have a PD-L1 tumor proportion score (TPS) ≥ 1% determined by IHC at the central laboratory. In order to balance patients with high PD-L1 expression (≥50%) and low PD-L1 expression (1-49%), we planned to enroll PD-L1 high and low patients at a ratio of 1:1.
• Have not received prior systemic treatment for NSCLC.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Expected survival ≥ 3 months.
• Adequate blood and organ function.

You may not qualify if:

• Patients with histologically confirmed squamous cell carcinoma, combined small cell carcinoma and large cell carcinoma.
• Molecular testing confirmed ALK translocation.
• Treatment with prior systemic cancer therapy for the current lung cancer at any time (chemotherapy, radiotherapy, target therapy, ablation, and any other local or systemic therapy).
• Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colorectal, endometrial, cervical, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
• Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications. Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
• Subjects with a history of interstitial lung disease, pneumonitis, or poorly controlled lung disease (including pulmonary fibrosis, acute lung diseases).
• Severe chronic or active infections that require systemic antimicrobial, antifungal, or antiviral treatment, including tuberculosis infections.
• Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL \[2500 copies/mL\] should be excluded.
• Has known active hepatitis C virus (HCV). Active HCV is defined by positive tests for HCV Ab and quantitative HCV RNA.
• Known positive history or positive test for Human Immunodeficiency Virus (HIV).
• The investigator believes that there is a high risk of bleeding (such as esophageal varices with bleeding risk, local active ulcer lesions) or active hemoptysis.
• History of allergy to study drug components.
• Pregnant and lactating women are excluded.
• Fertile men or their female partners (women of childbearing potential, WOCBP) who are not willing to use contraception.
• Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information.

Sponsors & Collaborators

• Ruijin Hospital: lead
• Guangdong Provincial People's Hospital: collaborator

Study Sites (2)

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510180, China

RECRUITING

Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Hecheng Li, PhD, MD

  Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hecheng Li, PhD, MD

CONTACT

00862164370045; lihecheng2000@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of thoracic department

Model Details: This study has only one arm, neoadjuvant Toripalimab treatment arm. Primary endpoint is MPR. We apply the optimal design of Simon's two-stage model to calculate the sample size and set both sides α= 0.05 and power=0.8, resulting in a total sample size of 29. Among them, 10 patients will be enrolled in the first stage. If the number of MPR cases in the first stage is less than or equal to 1, the study will be terminated in the early stage; On the contrary, participants in the second stage will continue to be enrolled. If the total number of MPR cases is greater than or equal to 5 after the completion of the second stage, the study is considered positive.

Study Record Dates

• First Submitted: February 12, 2024
• First Posted: February 21, 2024
• Study Start: April 20, 2024
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2030
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)