Clinical trial NCT06282536: Neoadjuvant Therapy With Iruplinalkib for Potentially Resectable ALK Positive NSCLC: A Single Arm, Exploratory Trial
Official title: Neoadjuvant Therapy With Iruplinalkib for Potentially Resectable ALK Positive Non-Small Cell Lung Cancer: A Single Arm, Exploratory Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Potentially Resectable ALK Positive Non-Small Cell Lung Cancer
Keywords: Non-Small Cell Lung Cancer
ALK
Iruplinalkib
Potentially Resectable Lung Cancer
Lead sponsor: Shanghai Pulmonary Hospital, Shanghai, China
Sponsor class: OTHER
First posted: 2024-02-28
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All enrolled patients received Iruplinalkib neoadjuvant therapy.
Primary purpose: TREATMENT

Brief summary: Fusion of anaplastic lymphoma kinase (ALK) is an important driving gene for NSCLC, with an incidence rate of 3-7%. In patients with advanced ALK mutation NSCLC, first-line use of ALK inhibitors significantly improves progression free survival. The perioperative research on ALK positive NSCLC was relatively late, and currently most studies mainly focus on early to mid stage ALK positive NSCLC patients. The results of two Phase III clinical trials showed that second-generation ALK targeted drugs, neoadjuvant and/or adjuvant therapy for ALK positive NSCLC, significantly prolonged DFS in patients, including increased pathological response rate, median response duration, and prolonged OS. For ALK positive advanced NSCLC patients who are resistant to second-generation ALK targeted drugs, there is currently limited exploration and there is an urgent need for new exploratory clinical studies.This trial aims to evaluate the effectiveness of Iruplinalkib neoadjuvant therapy for potentially resectable ALK positive non-small cell lung cancer.


Eligibility criteria: Inclusion Criteria:

* 1. The patient shall sign the Informed Consent Form. 2.Aged 18 ≥ years. 3.Histological or cytological diagnosis of NSCLC by needle biopsy, and evaluated by researchers as stage III-IVA, and diagnosed as ALK positive through genetic testing.

  4.Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1. 5. According to the MDT evaluation (which should include a thoracic surgeon specializing in tumor surgery), it is considered that the primary NSCLC is potentially completely resectable; 6. At least 1 measurable lesion according to RECIST 1.1. 7.Patients with good function of other main organs (liver, kidney, blood system, etc.) 8.Patients with lung function can tolerate surgery; 9.Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative. 10. Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 d

Exclusion Criteria:

* 1. Previously received targeted therapy (including TKI or monoclonal antibodies), immunotherapy, or any investigational drug treatment for NSCLC; 2.Pathological confirmation of mixed small cell and non-small cell lung cancer; 3.Patients with a malignancy other than NSCLC within five years prior to the start of this trial，except for cured basal cell carcinoma of the skin, early gastrointestinal (GI) carcinoma excised through endoscopy, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, or any cured cancer deemed to have no impact on the survival of the current NSCLC; 4.Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (\&gt;= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases; 5.Patients with congenital or acquired immune dysfunction (such as HIV infected individuals); 6.Received other major surgical treatments (excluding diagnosis) within 4 weeks prior to the start of the study or expected to undergo major surgical treatments during the study period; 7.Participants who are allergic to the test drug or any auxiliary materials; 8.A history of extensive diffuse bilateral interstitial fibrosis in the past or before medication, or a known grade 3 or 4 history of interstitial fibrosis or interstitial lung disease, including pneumonia, allergic pneumonia, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not including local radiation pneumonia or radiation pulmonary fibrosis history;8. Pregnant or lactating women; 9.Any malabsorption; 10.Participants suffering from nervous system diseases or mental diseases that cannot cooperate 11.Other factors that researchers think it is not suitable for enrollment.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 30 months
Secondary outcomes:
measure: Pathologic complete response (PCR) rate
timeFrame: Up to 30 months
measure: Major pathologic response (MPR) rate
timeFrame: Up to 30 months
measure: Overall survival (OS)
timeFrame: up to 60 months
measure: Event-free survival (EFS)
timeFrame: up to 60 months
measure: Treatment-related adverse event (TRAE)
timeFrame: Up to 30 months
measure: 5-year overall survival (OS)
timeFrame: Up to 72 months
measure: 1-year event-free survival (EFS) rate
timeFrame: Up to 24 months
measure: Health related quality of life (HRQol)
timeFrame: Up to 36 months
Other outcomes:
Locations:
Study officials:
References: