Plasma Molecular Profiling in ALK Inhibitor Resistant NSCLC

NCT04087473 | Completed DMC

• 1 other identifier: ATORG004
• Study Type: observational
• Target: 50
• Locations: 4 countries
• Sites: 5

Brief Summary

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.

Conditions

ALK-Positive Lung Cancer; Non-small Cell Lung Cancer

Keywords

ALK inhibitor (ALKi); NSCLC; 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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• 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

Study Arms (2)

Prior 2nd generation ALKi

Prior 1st and 2nd generation ALKi

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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):
• Adequate bone marrow function as shown by: ANC ≥ 1.0x10\^9/L, Platelets ≥ 75x10\^9/L, Hb ≥ 7.5 g/dL
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Guardant Health AMEA, Inc.: collaborator

Study Sites (5)

The Chinese University of Hong Kong

Hong Kong, Hong Kong

Location

University Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

National Cancer Center Singapore

Singapore, 169690, Singapore

Location

Asan Medical Centre

Seoul, 05505, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Biospecimen

Retention: SAMPLES WITH DNA

15-20mL of plasma

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Study Officials

• Daniel SW Tan, BSc, MBBS, PhD

  National Cancer Centre of Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2019
• First Posted: September 12, 2019
• Study Start: August 23, 2019
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

HK (1); KR (2); SG (1); MY (1)