search
Back to results

Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC

Primary Purpose

Non-Small Cell Lung Cancer, RET Driver Mutation, BRAF V600 Mutation

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Toripalimab
Nab paclitaxel
Pemetrexed
Carboplatin
Sponsored by
Guangdong Provincial People's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring Non-small Cell Lung Cancer, Neoadjuvant immunotherapy, Rare Mutations

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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.

Sites / Locations

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

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Toripalimab plus chemotherapy

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Major Pathological Response (MPR)
Percentage of Participants with Major Pathologic Response. MPR was defined as percentage of tumor cells within tumor bed less than 10% for both primary lung lesions and metastatic lymph nodes.
Event-Free Survival (EFS)
Event-free survival (EFS) is defined as the length of time from initiation of neoadjuvant treatment to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause.
Overall Survival (OS)
Overall survival (OS) is defined as the time between the date of initiation of neoadjuvant treatment and the date of death.
Adverse Events (AEs)
Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment or surgery.

Full Information

First Posted
March 21, 2023
Last Updated
April 4, 2023
Sponsor
Guangdong Provincial People's Hospital
Collaborators
Shanghai Junshi Bioscience Co., Ltd.
search

1. Study Identification

Unique Protocol Identification Number
NCT05800340
Brief Title
Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC
Official Title
Neoadjuvant Toripalimab Combined With Chemotherapy in Rare Mutations Stage IIB-IIIB NSCLC
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 4, 2023 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guangdong Provincial People's Hospital
Collaborators
Shanghai Junshi Bioscience Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.
Detailed Description
30 eligible patients will be enrolled and 3 cycles of Toripalimab 240mg + chemotherapy (Nab-paclitaxel + carboplatin, or pemetrexed + carboplatin) will be administered. Rare mutations include RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients who showed inferior response to neoadjuvant treatment leading to unresectable disease will be scheduled for local radiation or other potential subsequent treatment regarding multidisciplinary discussion. After completion of local treatment (surgery or radiation), patients will be provided with optional adjuvant treatment including chemotherapy or/and rare mutations TKI upon investigators' consideration. The primary objective of the study is pathological complete response (pCR) defined as no residue tumor found in both primary lung cancer and metastatic lymph nodes.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Toripalimab plus chemotherapy
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Toripalimab
Intervention Description
240mg Q3W
Intervention Type
Drug
Intervention Name(s)
Nab paclitaxel
Intervention Description
135 mg/m2, d1, 8 Q3W
Intervention Type
Drug
Intervention Name(s)
Pemetrexed
Intervention Description
500mg/m2, d1 Q3W
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
AUC 5, d1 Q3W
Primary Outcome Measure Information:
Title
Pathological Complete Response (pCR)
Description
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.
Time Frame
pCR will be assessed within 2 weeks after surgery
Secondary Outcome Measure Information:
Title
Major Pathological Response (MPR)
Description
Percentage of Participants with Major Pathologic Response. MPR was defined as percentage of tumor cells within tumor bed less than 10% for both primary lung lesions and metastatic lymph nodes.
Time Frame
MPR will be assessed within 2 weeks after surgery
Title
Event-Free Survival (EFS)
Description
Event-free survival (EFS) is defined as the length of time from initiation of neoadjuvant treatment to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause.
Time Frame
From date of initiation of neoadjuvant treatment to disease progression, reoccurrence, or death due to any cause, up to 36 months.
Title
Overall Survival (OS)
Description
Overall survival (OS) is defined as the time between the date of initiation of neoadjuvant treatment and the date of death.
Time Frame
From date of initiation of neoadjuvant treatment to the date of all-cause death, assessed up to 60 months.
Title
Adverse Events (AEs)
Description
Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment or surgery.
Time Frame
From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wen-Zhao Zhong, Ph.D
Phone
+86 02083827812
Email
syzhongwenzhao@scut.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Rui Fu, Ph.D
Phone
+86 02083827812
Email
ruifu66@foxmail.com
Facility Information:
Facility Name
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences
City
Guanzhou
State/Province
Guangdong
ZIP/Postal Code
510080
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wen-Zhao Zhong, Ph.D
Phone
+86 02083827812
Email
syzhongwenzhao@scut.edu.cn
First Name & Middle Initial & Last Name & Degree
Rui Fu, Ph.D
Phone
+86 02083827812
Email
ruifu66@foxmail.com
First Name & Middle Initial & Last Name & Degree
Wen-Zhao Zhong, Ph.D
First Name & Middle Initial & Last Name & Degree
Rui Fu, Ph.D
First Name & Middle Initial & Last Name & Degree
Chao Zhang, Ph.D

12. IPD Sharing Statement

Learn more about this trial

Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC

We'll reach out to this number within 24 hrs