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

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.

Sex

All

Minimum age

18 Years

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

• RESULTLawrence 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. PMID 34590008