# Study of Plasma Next Generation Sequencing for Remote Assessment, Characterization, Evaluation of Patients with ALK Drug Resistance (SPACEWALK)

> **NIH NIH R21** · DANA-FARBER CANCER INST · 2020 · $191,944

## Abstract

Project Summary/Abstract
Non-small cell lung cancers harboring fusions in the anaplastic lymphoma kinase (ALK) gene make up
approximately 4% of non-small cell lung cancers (NSCLC), thus representing thousands of the ~200,000 lung
cancers annually diagnosed in the United States. Patients with ALK-positive lung cancers can have dramatic
and durable responses to ALK-targeted tyrosine kinase inhibitors (TKIs), however acquired drug resistance is
inevitable after a median of 1-2 years. Several potent next generation ALK TKIs (e.g. ceritinib, alectinib,
brigatinib) are now FDA approved and are improving treatment outcomes in ALK-positive NSCLC. However,
the rarity of ALK-positive NSCLC has limited our ability to understand and develop management strategies for
ALK TKI resistance.
The SPACEWALK study leverages genomic analysis of plasma cell-free DNA (cfDNA) to study ALK TKI
resistance remotely from NSCLC patients developing resistance to next-generation ALK TKIs. Our center has
used remote consent and specimen collection extensively over recent years to study rare lung cancer
genotypes. We also have led the development and validation of assays for genotyping of plasma cfDNA. In this
study we combine these approaches to study a rare lung cancer population where precision treatment of has
the potential to improve patient outcomes. Eligible patients are screened remotely and consent via a web-
based system. Blood is collected and submitted for plasma next-generation sequencing (NGS) at a clinical
laboratory. Results are returned within 1-2 weeks to the patient and their oncologist and describe the potential
clinical implications of any resistance mutations detected. The patient is then followed to study the clinical
outcome on subsequent treatments received. A follow-up plasma specimen is collected 2-3 weeks after
starting therapy to evaluate response in plasma cfDNA.
Our overarching hypothesis is that such a remote participation study using plasma NGS will enrich our
understanding of resistance mutations in ALK-positive lung cancer, while also assessing value of plasma NGS
in predicting benefit from different ALK TKIs. Moreover, this novel methodology has the potential to be applied
widely across a range of cancer genotypes, dramatically impacting our ability to study (and thus develop
treatments for) cancer patients with targeted therapy resistance.

## Key facts

- **NIH application ID:** 9834846
- **Project number:** 5R21CA234816-02
- **Recipient organization:** DANA-FARBER CANCER INST
- **Principal Investigator:** Mark M. AWAD
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $191,944
- **Award type:** 5
- **Project period:** 2018-12-15 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9834846

## Citation

> US National Institutes of Health, RePORTER application 9834846, Study of Plasma Next Generation Sequencing for Remote Assessment, Characterization, Evaluation of Patients with ALK Drug Resistance (SPACEWALK) (5R21CA234816-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9834846. Licensed CC0.

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