A Window of Opportunity Study for Investigating Drug Tolerant Persister (DTP) to Preoperative Brigatinib in Resectable Non-small Cell Lung Cancer (NSCLC) Harboring ALK Fusions.

NCT05361564 | Unknown Phase 2

• 1 other identifier: 2022-0569-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study is single arm, open label, phase II trial for resectable ALK+ NSCLC. Eligible patients will receive brigatinib after 7-day lead-in 90mg from 4 to 10 weeks. The objective of this study is as follows.

• Primary objective: To identify molecular mechanism of DTP causing innate drug resistance to neoadjuvant brigatinib in resectable NSCLC harboring ALK fusion by analyzing single cell RNA-seq.
• Secondary objectives:
• To assess the pathologic response rate to neoadjuvant treatment with Brigatinib
• To evaluate the clinical efficacy in resectable ALK-positive NSCLC patients treated with brigatinib induction therapy
• To evaluate the successful curative resection rate
• To evaluate the safety of brigatinib as neoadjuvant treatment in resectable ALK-rearranged NSCLC patients.
• To investigate the changes of ALK rearrangement and other hot spot mutations by GUARDANT LUNAR assay of circulating tumor DNA present in blood plasma immediately with serial sampling.
• To assess of variant allele frequencies between pre-treatment and post-treatment sampling by GUARDANT LUNAR assay
• To explore cell-free biomarkers that may be predictive of response or primary resistance to brigatinib neoadjuvant therapy

Conditions

Non-small Cell Lung Cancer

Keywords

NSCLC; neo-adjuvant; ALK fusion; drug tolerant persister(DTP)

Outcome Measures

Primary Outcomes (1)

• molecular candidates identified by analyzing scRNA-seq

  Molecular candidates identified by analyzing scRNA-seq from pre-treatment tumor biopsy specimens and tumor tissue acquired at the time of surgical resection.

  10weeks (after surgery)

Secondary Outcomes (10)

• Pathologic complete response rate (pCR)

  10weeks (after surgery)

• Major pathologic response (MPR)

  10weeks (after surgery)

• Disease-free survival (DFS)

  Up to 2 years

• Event free survival (EFS)

  Up to 2 years

• Overall survival (OS)

  6months

Study Arms (1)

Brigatinib

EXPERIMENTAL

Drug: Brigatinib

Interventions

Brigatinib DRUG

After 7-day lead-in 90mg/day, brigatinib 180mg/day from 4 to 10weeks(optimal duration: 6 weeks)

Brigatinib

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients 20 years or older.
• Voluntary written consent must be given before performance of any study related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
• Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
• Agree to practice effective barrier contraception during the entire study treatment period and through 4 months after the last dose of study drug, or
• Agree to completely abstain from heterosexual intercourse
• Treatment-naïve stage I to IIIa non-small cell lung cancer according to the AJCC 8th edition and amenable to surgical resection.
• Documented ALK rearrangement (VENTANA ALK (D5F3) CDx Assay or appropriate diagnostic method)
• Brain magnetic resonance imaging (MRI) (or CT if contraindication to MRI) within the last 60 days showing no evidence of metastatic disease
• Eastern Cooperative Oncology Group (ECOG) performance status and/or other performance status 0 or 1
• Documentation that the patient is a candidate for surgical resection of their lung cancer by certified surgeon.
• Measurable disease defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria

You may not qualify if:

• Clinical stage IIIb or IIIc or distant metastases (including malignant pleural effusion) identified in CT, PET-CT, brain imaging or biopsy.
• Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
• Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol
• Treatment with any investigational products within 4 weeks before the first dose of study drug
• Had major surgery within 30 days of the first dose of brigatinib. Minor surgical procedures such as catheter placement or minimally invasive biopsies are allowed.
• Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated nonmelanoma skin cancer or cervical cancer in situ; definitively treated nonmetastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• Have symptomatic brain metastasis (parenchymal or leptomeningeal). Patients with asymptomatic brain metastasis or who have stable symptoms that did not require an increased dose of corticosteroids to control symptoms in the past 7 days before the first dose of brigatinib may be enrolled.
• Have current spinal cord compression (symptomatic or asymptomatic and detected by radiographic imaging). Patients with leptomeningeal disease and without cord compression are allowed.
• Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
• Myocardial infarction within 6 months before the first dose of brigatinib.
• Unstable angina within 6 months before first dose of brigatinib.
• Congestive heart failure within 6 months before first dose of brigatinib.
• History of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician.
• Any history of clinically significant ventricular arrhythmia.
• Had a cerebrovascular accident or transient ischemic attack within 6 months before first dose of brigatinib.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Yonsei University Health System, Severance Hospital

Seoul, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

brigatinib

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Hye Ryun Kim

CONTACT

+82-2-2228-8125; nobelg@yuhs.ac

Study Design

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

Study Record Dates

• First Submitted: April 29, 2022
• First Posted: May 4, 2022
• Study Start: June 1, 2022
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2024
• Last Updated: May 4, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)