FDA Approves Companion Diagnostic for Identification of NTRK Fusions in Solid Tumors


The FDA granted approval to the FoundationOne®CDx as a companion diagnostic for the identification of NTRK fusions across all solid tumors for the approved larotrectinib.

The FDA has granted approval to the FoundationOne®CDx as a companion diagnostic for the identification of NTRK fusions across all solid tumors for the approved larotrectinib (Vitrakvi) treatment of adult and pediatric patients with solid tumors harboring an NTRK fusion without a known acquired resistance mutation, are metastatic or where surgical resection is likely to cause severe morbidity, and have no satisfactory alternative treatments or have progressed following prior treatment, according to a press release from Foundation Medicine, Inc.1

FoundationOne CDx is the only FDA-approved tissue-based comprehensive genomic profiling test, now approved for the detection of NTRK1/2/3 fusions across all solid tumors to identify patients who may be appropriate for larotrectinib therapy.

“Taking a comprehensive and validated approach to genomic testing is critical for all advanced cancer patients, but especially for those harboring rare mutations that can be missed with alternative testing methods,” said Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine, in a statement. “Not only will this approval improve access to genomic testing and reinforce the role it plays in rare cancers, but it also confirms the incredible progress made toward tumor-agnostic cancer care. We’re proud of the impact this will have on NTRK fusion-positive cancer patients.”

NTRK fusions occur when a part of the NTRK gene-containing chromosome breaks off and binds to another chromosome, and these fusions produce TRK fusion proteins known to cause cancer cell growth. These fusions are more common in rare cancer types, such as secretory carcinoma of the breast or salivary gland and infantile fibrosarcoma, but NTRK fusions can occur in more common types of cancer as well, including glioma, melanoma, and carcinomas of the lung, thyroid, and colon.

FoundationOne CDx, the only FDA-approved companion diagnostic that is clinically and analytically validated for solid tumors, is currently approved as a companion diagnostic for over 20 different targeted therapies, including this indication for larotrectinib.

“Many patients with rare conditions, like NTRK fusion-positive cancer have limited treatment options and poor access to targeted therapies,” stated Susan Spinosa, co-chair and patient founder of the NTRKers. “This companion diagnostic approval is a critical step forward in addressing this challenge as it provides this patient population with broader access to comprehensive genomic testing and appropriate treatment options.”

Larotrectinib received its approval from the FDA in November 2018 based on findings from 3 clinical trials, including LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431). Positive NTRK gene fusions were prospectively determined in local laboratories with next-generation sequencing or fluorescence in situ hybridization (FISH), and NTRK gene fusions were identified in 3 pediatric patients with infantile fibrosarcoma who had documented ETV6 translocation by FISH.

Major efficacy outcomes included overall response rate (ORR) and response duration, which was determined by a Blinded Independent Review Committee according to RECIST 1.1 criteria. The clinical validation of FoundationOne CDx was achieved through a clinical bridging study between the local clinical trial assays and FoundationOne CDx.

According to updated findings from the 3 studies, which were published in The Lancet in March 2020, the ORR was 79% (95% CI, 72%-85%) among 153 evaluable patients, and complete responses occurred in 16%, partial responses in 63%. Stable disease was the best response in 12% of patients, which led to a 91% clinical benefit rate.2

The most common any-grade treatment-related adverse events (TRAEs) included increased alanine aminotransferase (ALT)/aspartate transaminase level (AST; 38%), dizziness (25%), fatigue (16%), nausea (16%), constipation (16%), vomiting (11%), increased body weight (11%), anemia (9%), decreased neutrophil count (9%), and diarrhea (5%). Grade 3 TRAEs included increased ALT/AST level (5%), anemia (2%), decreased neutrophil count (2%), nausea (2%), and dizziness (2%). No grade 4/5 TRAEs were observed, and dose reductions were required in 8 patients.

FoundationOne CDx can detect substations, insertion or deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, and it can also detect genomic signatures including microsatellite instability and tumor mutational burden by using DNA isolated from formalin-fixed paraffin embedded tumor tissue specimens. The test is intended for prescription use only and as a companion diagnostic for the identification of patients who may benefit from select targeted therapies, in accordance with approved therapeutic product labeling.1

The assay is also intended for use by qualified health care professionals as a test that can provide tumor mutation profiling that can be used in accordance with professional guidelines in oncology for the treatment of patients with solid malignant neoplasms. It is noted that the use of FoundationOne CDx does not guarantee a patient will be matched to a targeted treatment, and a negative result may not rule out the presence of an alteration, in which case some patients may require a biopsy.


1. FoundationOne®CDx Receives FDA-Approval as a Companion Diagnostic for VITRAKVI®(larotrectinib) to Identify Patients with NTRK Fusions Across All Solid Tumors. News Release. Foundation Medicine, Inc. October 23, 2020. Accessed October 26, 2020. https://bit.ly/2TqMLKW

2. Hong DS, DuBois SG, Kummar S. Larotrectinib in patients with TRK fusion-positive solid tumours: a pooled analysis of three phase 1/2 clinical trials. Lancet Oncol. doi: 10.1016/S1470-2045(19)30856

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