Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC

NCT05800340 | Recruiting Phase 2

• 1 other identifier: NEORM
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Toripalimab plus chemotherapy in rare mutations stage IIB-IIIB NSCLC followed by optional adjuvant treatment upon investigators' decisions.

Conditions

Non-Small Cell Lung Cancer; RET Driver Mutation; BRAF V600 Mutation; Erb-B2 Receptor Tyrosine Kinase Exon 20 Mutation; MET Amplification; MET Exon 14 Skipping Mutation

Keywords

Non-small Cell Lung Cancer; Neoadjuvant immunotherapy; Rare Mutations

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR)

  Evaluation of the pathological complete response: The pathological complete response is defined as the absence of residual tumor in both lung and lymph nodes after neoadjuvant treatment.

  pCR will be assessed within 2 weeks after surgery

Secondary Outcomes (4)

• Major Pathological Response (MPR)

  MPR will be assessed within 2 weeks after surgery

• Event-Free Survival (EFS)

  From date of initiation of neoadjuvant treatment to disease progression, reoccurrence, or death due to any cause, up to 36 months.

• Overall Survival (OS)

  From date of initiation of neoadjuvant treatment to the date of all-cause death, assessed up to 60 months.

• Adverse Events (AEs)

  From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.

Study Arms (1)

Toripalimab plus chemotherapy

EXPERIMENTAL

3 cycles of neoadjuvant Toripalimab (240mg every 3 weeks) with nab-paclitaxel + carboplatin, or pemetrexed + carboplatin (decided by investigators; nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every 3 weeks; pemetrexed, 500mg/m2 d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including chemotherapy for 3-4 cycles or rare mutations-TKIs for up to 2 years or till disease progression or unacceptable toxicity.

Biological: Toripalimab; Drug: Nab paclitaxel; Drug: Pemetrexed; Drug: Carboplatin

Interventions

Toripalimab BIOLOGICAL

240mg Q3W

Toripalimab plus chemotherapy

Nab paclitaxel DRUG

135 mg/m2, d1, 8 Q3W

Toripalimab plus chemotherapy

Pemetrexed DRUG

500mg/m2, d1 Q3W

Toripalimab plus chemotherapy

Carboplatin DRUG

AUC 5, d1 Q3W

Toripalimab plus chemotherapy

Eligibility Criteria

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

You may qualify if:

• Age: 18 Years and older
• ECOG physical score 0-1 points; expected survival time ≥ 3 months;
• Pathologically confirmed diagnosis with Stage IIB-IIIB NSCLC which harbored rare driver alteration including RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Suspected N2 disease should be confirmed by either mediastinoscopy or EBUS. N1 disease could be determined through PET/CT but biopsy of primary lung cancer is needed;
• Lung function capacity capable of tolerating the proposed lung surgery
• Available tissue of tumor for PD-L1 test
• Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.

You may not qualify if:

• Stage I and stage IV NSCLC;
• Patients who have previously used any other anti-tumor drugs or radiotherapy;
• Large panel NGS indicated sensitive EGFR alteration, ALK fusion, ROS1 fusion or any other driver mutations combined with MDM2/MDM4 amplification;
• Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
• A history of active bleeding within the 6 months before enrollment, or receiving thrombolysis or anticoagulant therapy, or the investigator believes that there is a clear tendency to gastrointestinal bleeding (such as esophageal varices with bleeding risk, local activity) Ulcer lesions, etc.) or active hemoptysis;
• Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections; Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
• Known or suspected autoimmune disease with activity. Participants may be enrolled if they have type 1 diabetes, hypothyroidism that requires only hormone replacement therapy, skin diseases that require no systemic treatment (such as purpura, psoriasis, or hair loss), or other conditions that are not expected to return without external trigger.
• Patients with active hepatitis B (positive for HBsAg) or hepatitis C (positive for HCV RNA).
• Patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
• Patients with other active malignancies within five years
• Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
• Patients with low compliance or willingness to take the drugs and surveillance.

Sponsors & Collaborators

• Guangdong Provincial People's Hospital: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences

Guanzhou, Guangdong, 510080, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

toripalimab; Taxes; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Central Study Contacts

Wen-Zhao Zhong, Ph.D

CONTACT

+86 02083827812; syzhongwenzhao@scut.edu.cn

Rui Fu, Ph.D

CONTACT

+86 02083827812; ruifu66@foxmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 3 cycles of neoadjuvant Toripalimab (240mg every 3 weeks) with nab-paclitaxel + carboplatin, or pemetrexed + carboplatin (decided by investigators; nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every 3 weeks; pemetrexed, 500mg/m2 d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including chemotherapy for 3-4 cycles or rare mutations-TKIs for up to 2 year or till disease progression or unacceptable toxicity.

Study Record Dates

• First Submitted: March 21, 2023
• First Posted: April 5, 2023
• Study Start: April 4, 2023
• Primary Completion: December 31, 2024
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 5, 2023

Record last verified: 2023-03

Locations

CN (1)