FDA Approves FoundationOne CDx for ROS1 Fusion–Positive NSCLC and NTRK Fusions


The FoundationOne CDx has been granted approval by the FDA to identify patients with ROS1 fusion–positive non–small cell lung cancer or NTRK fusion–positive cancers who might be candidates for entrectinib.

The FDA has granted approval to the FoundationOne companion diagnostic (CDx) which will be used to identify patients with ROS1 fusion–positive non–small cell lung cancer (NSCLC) or NTRK fusion–positive cancers who may benefit from entrectinib (Rozlytrek), according to Roche.1

The basis of the approval comes from data of the phase 1 ALKA-372-001 (EudraCT 2012-000148-88), phase 1 STARTRK-1 (NCT02097810), and phase 2 STARKTRK-2 (NCT02568267) trials where a majority of patients received 600 mg of entrectinib once a day.

“The ability to tailor cancer therapies based on specific genomic alterations using validated comprehensive genomic profiling has transformed the traditional ‘one-size fits-all’ approach to cancer,” stated Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, in the press release. “This approval marks a significant step forward in expanding treatment options and improving outcomes for patients, particularly those with rare tumors.”

This comprehensive genomic profiling pan-tumor tissue biopsy test is the first CDx to get the greenlight by the FDA for these diseases.

Entrectinib was approved by the FDA in 2019 with the intent to treat patients with ROS1 fusion–positive metastatic NSCLC. The targeted therapy is also a tumor-agnostic medicine that can help treat locally advanced or solid tumors harboring NTRK gene fusions.

In patients with NSCLC, ROS1 gene fusions are identified in 1%-2% of patients. Further, NTRK gene fusions have been seen among a variety of solid tumor types, occurring in 90% of some rare cancer types and less than 1% of other more common cancers.

An integrated analysis of all 3 trials (ALKA-372-001, STARTRK-1, STARKTRK-2) which assessed 74 patients with NTRK1/2/3 fusion–positive solid tumors, had a median follow-up of 14.2 months (range 0.1-29.7). The overall response rate (ORR) demonstrated was 63.5% (95% CI, 51.5%-74.4%), according to blinded independent central review, and there were a total of 5 (6.8%) complete responses (CRs) observed.2

Median duration of response (DOR) was 12.9 months (95% CI, 9.3-not evaluable [NE]), and the median progression-free survival was 11.2 months (95% CI, 8.0-15.7) with a median overall survival of 23.9 months (95% CI, 16.0-NE). The 55 patients who did not have investigator-assessed central nervous system (CNS) disease at baseline had an ORR of 65.5% (95% CI, 51.4%-77.8%).

Additionally, the median DOR among those who responded to treatment was 12.9 months (95% CI, 9.30-NE). Patients who had baseline CNS disease (n = 19) demonstrated an ORR of 57.9% (95% CI, 33.5%-79.8%) and the median DOR in responders was 6.0 months (95% CI, 4.2-NE).

Investigators also evaluated patients with locally advanced or metastatic NTRK1/2/3 or ROS1 fusion–positive solid tumors, including NSCLC, colorectal, and other solid tumors, in another pooled analysis. Of the evaluable patients with NSCLC (n = 161), the ORR was 67.1% (95% CI, 59.3%-74.3%). Among these patients, 14 (8.7%) had CRs and 94 (58.4%) had partial responses. The median DOR was 15.7 months (95% CI, 13.9-28.6) and the median follow-up was 15.8 months.

In the study, a total of 24 patients received prior immunotherapy, and in that subgroup, there was an ORR of 70.8% (95% CI 48.9%-87.4%). Patients who had investigator-assessed CNS metastases at baseline had an ORR of 62.5% (95% CI, 48.6%-75.1%).

Previously in February 2022, the FDA approved FoundationOne CDx as a companion diagnostic to pembrolizumab (Keytruda) for patients with microsatellite instability–high solid tumors. The first approval for the tissue-based biopsy came in November 2017, and it is now approved as a CDx for 25 indications and 3 group claims across 30 targeted therapies.


  1. US FDA approves Foundation Medicine’s FoundationOne CDx as a companion diagnostic for Roche’s Rozlytrek (entrectinib). News release. Roche. June 9, 2022. Accessed June 9, 2022. https://bit.ly/3zvu3rN
  2. Rolfo CD, De Braud FG, Doebele RC, et al. Efficacy and safety of entrectinib in patients (pts) with NTRKfusion-positive (NTRK-fp) solid tumors: an updated integrated analysis. J Clin Oncol. 2020;38(suppl 15):3065. doi:10.1200/JCO.2020.38.15_suppl.3605
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