Study of Plasma NGS for Assessment, Characterization, Evaluation of Patients With ALK Resistance (SPACEWALK)

ALCMI-011: Study of Plasma Next Generation Sequencing for Assessment, Characterization, Evaluation of Patients With ALK Resistance (SPACEWALK)

ALK-positive lung cancer is a subtype of lung cancer which carries a change in a gene called ALK (anaplastic lymphoma kinase). There are now many drugs for patients with ALK-positive lung cancer that slow cancer growth. However, after some time, just as bacteria evolve resistance to antibiotics, ALK-positive lung cancers evolve ways to avoid the therapies by developing new mutations so the drugs lost their effectiveness. These new mutations can potentially be treated with a different drug. For these new therapies, the range of mutations that can develop at resistance is not well understood.

It is now possible to detect the presence of mutations or changes in the genetic structure in lung cancer by analyzing a patient's blood for bits of material shed by tumor. This approach is often called a liquid biopsy. Recently, researchers have shown that looking at tumor molecules through liquid biopsies can provide doctors with some of the same information that tissue biopsies provide. For example, liquid biopsies can be used to detect mutations that cause drug resistance. Obtaining liquid biopsies on patients with ALK-positive lung cancers at resistance to therapy may help better understand the different mutations that develop and guide therapy decisions.

In this research study, a blood specimen will be collected and submitted for liquid biopsy analysis at a commercial diagnostic company. This company specializes in analyzing tumor material found in blood. Specifically, it will look for genetic changes in the ALK gene that could help understand why a cancer has developed drug resistance.

This research study is for lung cancer patients with ALK-positive lung cancer who had been on a newer ALK targeted treatment (such as ceritinib, alectinib, brigatinib, or lorlatinib) to determine whether they have developed ALK resistance mutations. The investigators will collect a blood sample to examine these mutations. Participants will not have to have a tissue biopsy to participate in this study. Participants do not have to visit Dana-Farber Cancer Institute (DFCI) to participate. All study procedures will be performed remotely.

Study Overview

• Status: Completed
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Diagnostic test: Plasma Next Generation Sequencing (NGS)

Detailed Description

SPACEWALK is an innovative remote consent and participation study using next-generation sequencing (NGS) of plasma cell-free DNA (cfDNA) to characterize resistance mechanisms arising in ALK-positive non-small cell lung cancer (NSCLC) after progression while on a next generation ALK tyrosine kinase inhibitor (TKI). Additionally, the study will capture the potential of genomic-driven resistance therapy approach for effecting outcomes in patients with advanced ALK-positive NSCLC and TKI resistance. Finally, the study will assess the role of repeat plasma NGS in evaluating drug response.

The study will accrue patients with advanced ALK-positive NSCLC on systemic progression (outside the brain) while on treatment with a next-generation ALK TKI. Any patient interested in the study will find information about the study on the study website. The patient will consent remotely through the study website and documentation of advanced ALK-positive NSCLC and systemic progression while on a next-generation ALK TKI. The study team will reach out to the patient to confirm eligibility and send a blood collection kit. In the study kit the study participants will find all the necessary materials for local blood draws, and collected specimens will be sent directly to the central study laboratory (Resolution Bioscience) for plasma NGS.

Plasma NGS of cfDNA will involve sequencing of 19 genes, including ALK, permitting remote tumor genotyping. Plasma NGS analysis and results will be done following standard procedures of the Resolution Bioscience CLIA-certified laboratory. Results will be sent to study participants, their physicians and study team within 1-2 weeks. Plasma NGS reports will not include any specific treatment recommendations but will describe the presence of an ALK rearrangement, ALK resistance mutation, or other relevant mutations.

Study participants are followed remotely. The study coordinator will contact the participants weekly for 4 weeks after enrolled into the study to learn of any new treatment initiation and to release an additional plasma collection kit 2-4 weeks after starting treatment. Study participants will then be remotely contacted every 3 months to follow clinical outcomes on therapy for up to 2 years. If the cancer progresses on the participant's new treatment, the patient will have the option to provide a third blood specimen. Medical records and local imaging will be collected and studied.

The primary objective of the study is to characterize ALK TKI resistance to next-generation ALK TKIs in patients with advanced ALK-positive NSCLC. Secondarily, the investigators will assess the potential of plasma NGS to impact outcome on treatment by studying time to treatment discontinuation. Serial plasma NGS will also be assessed as a response biomarker. A total of 300 patients are planned to be enrolled, with the expectation that approximately 200 will have tumor-related mutations detected in plasma NGS.

• Study Type: Observational
• Enrollment (Actual): 62

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This research study is for lung cancer patients with ALK-positive lung cancer who had been on a newer ALK targeted treatment (such as ceritinib, alectinib, brigatinib, or larlatinib).

Description

Inclusion Criteria:

• Men or women older than 18 years at the time of consent.
• Demonstration of having advanced ALK positive NSCLC.
• Systemic progression (not CNS only progression) within the past 30 days while receiving a next generation ALK TKI.
• Patient must not have started a new line of therapy before signing the informed consent form.
• Willingness to provide a blood specimen prior to the initiation of a new line of treatment.
• Willing to provide clinical and medical information to the study team as required.
• Ability to read, write and communicate in English.
• Ability to sign a web-based informed consent form.

Exclusion Criteria:

• Participants who are unable to provide informed consent.
• Participants who are 18 years of age or younger.
• Participants who are unable to comply with the study procedures.
• Known existence of an uncontrolled intercurrent illness including, but not limited to, psychiatric illness or social situations that would impair compliance with study requirements.
• Participants who have previously enrolled to the study

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ALK-positive NSCLC with progression; Patients in this group signed consent, met eligibility criteria, and all had ALK-positive cancer of a primary lung lesion with systemic progression (excluding the central nervous system)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of ALK Fusion	To determine the prevalence of the ALK gene fusion in the cohort of patients with ALK-positive NSCLC with progression	32 months
ALK Fusion Allelic Frequency	To determine the relative percentage of the ALK fusion within the cohort's gene pool	32 months
Overall Prevalence of ALK Resistance Mechanism Among Patients With the ALK Fusion	To determine the overall prevalence of ALK resistance mechanism in patients with detectable ALK fusion in plasma as determined per plasma NGS	32 months
Type of Resistance Mechanism: One or More Secondary ALK Kinase Domain Resistance Mutations	To determine the prevalence of the various types of ALK resistance mechanisms as measured by NGS	32 months
Type of ALK Resistance Mechanism: Both ALK Resistance Mutations and Bypass Resistance	To determine the prevalence of the various types of ALK resistance mechanisms as measured by NGS	32 months
Prevalance of ALK Restance Mechanism: Bypass Track Resistance	To determine the prevalence of the various types of ALK resistance mechanisms as measured by NGS	32 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changed Treatment for NSCLC	Initiated a new ALK tyrosine kinase inhibitor for treatment of NSCLC following enrollment in the study	32 months
Treatment Outcome: >50% Reduction of ALK Fusion Allelle Frequency	New ALK TKI treatment resulted in >50% reduction of ALK fusion allelle frequency	32 months

Collaborators and Investigators

• Sponsor: Addario Lung Cancer Medical Institute
• Collaborators: National Cancer Institute (NCI); Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Geoffrey R Oxnard, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• Lawrence MN, Tamen RM, Martinez P, Sable-Hunt A, Addario T, Barbour P, Shaffer T, Hosseini SA, Bertucci C, Lim LP, Hong F, Michael K, Simon GR, Riess JW, Awad MM, Oxnard GR. SPACEWALK: A Remote Participation Study of ALK Resistance Leveraging Plasma Cell-Free DNA Genotyping. JTO Clin Res Rep. 2021 Feb 3;2(4):100151. doi: 10.1016/j.jtocrr.2021.100151. eCollection 2021 Apr.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2019
• Primary Completion (Actual): October 31, 2023
• Study Completion (Actual): October 31, 2023

Study Registration Dates

• First Submitted: January 28, 2019
• First Submitted That Met QC Criteria: February 6, 2019
• First Posted (Actual): February 7, 2019

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: ALK positive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: ALCMI-011; 5R21CA234816 (U.S. NIH Grant/Contract)

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