Trial Title:
Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC
NCT ID:
NCT05800340
Condition:
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
Conditions: Official terms:
Carcinoma, Non-Small-Cell Lung
Paclitaxel
Carboplatin
Pemetrexed
Conditions: Keywords:
Non-small Cell Lung Cancer
Neoadjuvant immunotherapy
Rare Mutations
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention 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.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Toripalimab
Description:
240mg Q3W
Arm group label:
Toripalimab plus chemotherapy
Intervention type:
Drug
Intervention name:
Nab paclitaxel
Description:
135 mg/m2, d1, 8 Q3W
Arm group label:
Toripalimab plus chemotherapy
Intervention type:
Drug
Intervention name:
Pemetrexed
Description:
500mg/m2, d1 Q3W
Arm group label:
Toripalimab plus chemotherapy
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
AUC 5, d1 Q3W
Arm group label:
Toripalimab plus chemotherapy
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age: 18 Years and older
2. ECOG physical score 0-1 points; expected survival time ≥ 3 months;
3. 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;
4. Lung function capacity capable of tolerating the proposed lung surgery
5. Available tissue of tumor for PD-L1 test
6. Subjects voluntarily joined the study and signed informed consent, with good
compliance to follow-up.
Exclusion Criteria:
1. Stage I and stage IV NSCLC;
2. Patients who have previously used any other anti-tumor drugs or radiotherapy;
3. Large panel NGS indicated sensitive EGFR alteration, ALK fusion, ROS1 fusion or any
other driver mutations combined with MDM2/MDM4 amplification;
4. Histologically confirmed small cell lung cancer (including lung cancer mixed with
small cell lung cancer and non-small cell lung cancer);
5. 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;
6. 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;
7. 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.
8. Patients with active hepatitis B (positive for HBsAg) or hepatitis C (positive for
HCV RNA).
9. Patients with human immunodeficiency virus (HIV) or acquired immunodeficiency
syndrome (AIDS)
10. Patients with other active malignancies within five years
11. Pregnant or lactating women; those who have fertility are unwilling or unable to
take effective contraceptive measures;
12. Patients with low compliance or willingness to take the drugs and surveillance.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences
Address:
City:
Guanzhou
Zip:
510080
Country:
China
Status:
Recruiting
Contact:
Last name:
Wen-Zhao Zhong, Ph.D
Phone:
+86 02083827812
Email:
syzhongwenzhao@scut.edu.cn
Contact backup:
Last name:
Rui Fu, Ph.D
Phone:
+86 02083827812
Email:
ruifu66@foxmail.com
Investigator:
Last name:
Wen-Zhao Zhong, Ph.D
Email:
Principal Investigator
Investigator:
Last name:
Rui Fu, Ph.D
Email:
Sub-Investigator
Investigator:
Last name:
Chao Zhang, Ph.D
Email:
Principal Investigator
Start date:
April 4, 2023
Completion date:
December 31, 2026
Lead sponsor:
Agency:
Guangdong Provincial People's Hospital
Agency class:
Other
Collaborator:
Agency:
Shanghai Junshi Bioscience Co., Ltd.
Agency class:
Other
Source:
Guangdong Provincial People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05800340
