Plasma Molecular Profiling in ALK Inhibitor Resistant NSCLC

Plasma Molecular Profiling in ALK Inhibitor Resistant Non-Small Cell Lung Cancer

The investigators plan to understand a comprehensive molecular profiling via the plasma, with the primary aim of using this form on analysis to guide subsequent treatment selection. This study will provide a better understanding of ALK resistance in the treatment of Asian lung cancers and allow for improved clinical outcomes by 'matching' the secondary mutations to an ALK inhibitor which would allow for the greatest coverage ultimately leading to lasting duration of response.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer; ALK-Positive Lung Cancer

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Justine Chu; Phone Number: +65 64368000; Email: justine.chu.j.h@nccs.com.sg

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Not yet recruiting
    • The Chinese University of Hong Kong
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Not yet recruiting
    • Asan Medical Centre
• Malaysia
  • Kuala Lumpur, Malaysia
    • Not yet recruiting
    • University Malaya Medical Centre
• Singapore
  • Singapore, Singapore, 169690
    • Recruiting
    • National Cancer Center Singapore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Two cohorts will be enrolled, the first cohort will consist of patients that have received prior 2nd generation ALKi only, and the second cohort with patients that have received prior 1st and 2nd generation ALKi.

Description

Inclusion Criteria:

• Patients with advanced ALK fusion oncogene positive lung adenocarcinoma that have progressed after 1-2 ALK inhibitors, with at least one prior line of 2nd generation ALKi (i.e. Ceritinib, Alectinib, Brigatinib or Ensartinib)
• The availability of sufficient plasma
• Age ≥ 21 years
• WHO performance status ≤ 2
• Life expectancy of ≥ 21 weeks

• Patients should have adequate organ function for potential consideration into clinical trials (routine blood tests are valid within 14 days before enrollment):

  1. Adequate bone marrow function as shown by: ANC ≥ 1.0x10^9/L, Platelets ≥ 75x10^9/L, Hb ≥ 7.5 g/dL
  2. Alanine aminotransferase (ALT) and aspirate aminotransferase (AST) normal range (or ≤ 3.0xULN if liver metastases are present)
• Willing to provide signed informed consent
• Patients whom do not fulfill the above criteria may be discussed on a case-by-case basis within the study team, for potential enrolment

Exclusion Criteria:

• Received more than 2 prior ALK inhibitors (ALKi)
• Symptomatic or uncontrolled brain metastases requiring concurrent treatment inclusive but not limited to surgery and radiation. Stable/ tailing doses of corticosteroids is permitted

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Prior 2nd generation ALKi
Prior 1st and 2nd generation ALKi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Molecular profiling of plasma	Profiling of the collected plasma samples at a molecular level to evaluate the molecular epidemiology of ALK fusion oncogene positive lung cancer	2 to 4 weeks after collection of plasma

Secondary Outcome Measures

Outcome Measure	Time Frame
Patient survival status	After molecular profiling has been completed, every few months up to 2 years
Subsequent patient treatment status	After molecular profiling has been completed, every few months up to 2 years
Clinical outcomes of the subsequent treatments the patients receive	After molecular profiling has been completed, every few months up to 2 years

Collaborators and Investigators

• Sponsor: National Cancer Centre, Singapore
• Collaborators: Guardant Health AMEA, Inc.
• Investigators: Principal Investigator: Daniel SW Tan, BSc, MBBS, PhD, National Cancer Centre of Singapore

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: September 9, 2019
• First Submitted That Met QC Criteria: September 10, 2019
• First Posted (Actual): September 12, 2019

Study Record Updates

• Last Update Posted (Actual): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: NSCLC; ALK inhibitor (ALKi); Anaplastic lymphoma kinase (ALK) fusion oncogene NSCLC; Guardant360 assay; Next-Generation Sequencing (NGS) DNA sequencing test; Cell-free circulating tumor DNA (ctDNA); Plasma profiling; Blood-based assay; Mutational testing; 74 genetic alterations (point mutations, copy number variants, fusions, insertions, deletions); ALK resistance mutations
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ATORG004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No