FDA Approves FoundationOne CDx Companion Diagnostic for Entrectinib in ROS1+ NSCLC or NTRK+ Solid Tumors


FoundationOne CDx has been approved by the FDA as a companion diagnostic for entrecitinib for the treatment of ROS1 fusion–positive non–small cell cancer or NTRK fusion–positive solid cancers.

The FDA has approved FoundationOne CDx as a companion diagnostic for entrectinib (Rozlytrek), for patients with ROS1 fusion–positive non–small cell lung cancer (NSCLC) or NTRK fusion–positive solid malignancies, according to a press release from Roche.1

The approval is based on findings from several studies, including the phase 1 ALKA-372-001, phase 1 STARTRK-1 (NCT02097810), and phase 2 STARKTRK-2 (NCT02568267) trials. As part of the approval, the FDA has added a condition where a post-approval study must be conducted by the Flatiron Health-Foundation Medicine’s Clinico-Genomic Database to continue to identify patients with ROS1 fusion-positive NSCLC who would benefit from entrectinib.

“The ability to tailor cancer therapies based on specific genomic alterations using validated comprehensive genomic profiling (CGP) has transformed the traditional ‘one-size fits all’ approach to cancer,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, said 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.”


A total of 54 patients with advanced or metastatic solid tumors enrolled on the ALKA-372-001 trial, with a median age of 53 years. The majority were male, and 56% had an ECOG performance status of 0.2 In 94% of patients received 4 or more prior systemic therapies, and 19% had prior ROS1/ALK inhibitors. The most common tumor type was NSCLC.

For the trial, the dose schedules included 19 patients on schedule A, which had patients fast followed by 4 days of entrectinib and 3 days off for 21 of 28 days; 29 patients were on schedule B who were fed and received continuous dosing for 28 days; and 6 patients were on schedule C who were fed followed by 4 days on the study treatment and 3 days off for 28 days.

The most common adverse effects (AEs) included fatigue (46%), dysgeusia (42%), paresthesia (29%), nausea (28%), and myalgia (23%). No patients experienced dose-limiting toxicities, with grade 3 cognitive disturbance and fatigue being resolved with dose interruption. Of those receiving 800 mg dose level, 1 patient had grade 4 eosinophilic myocarditis.


Patients with TrkA, TrkB, TrkC, ROS1, and ALK molecular alterations were treated with entrectinib as part of the STARTRK-1 trial. The primary end points included dose-limiting toxicities, maximum tolerated dose, recommended phase 2 dose, and overall response rate. The secondary end points were plasma concentrations of entrectinib, disease control, duration of response (DOR), overall survival, and progression-free survival.

The median age of patients (n = 65) was 57, a majority were male, and 63% had an ECOG performance status of 1. Prior systemic therapies were used in 39% of patients and ranged between 3 to 4 lines. Additionally, 34% of prior treatments were ROS1/ALK inhibitors. The most common tumor type was NSCLC.

All patients received continuous daily dosing of study treatment for 28 days. Two dose-limiting toxicities occurred in the trial at a daily dose of 800 mg.


The STARTRK-2 trial was a basket study that included with patients with solid tumors harboring NTRK 1/2/3, ROS1, or ALK gene fusions. Patients were assigned to specific baskets based on tumor type and gene fusion. The primary end point was objective response rate, and the secondary end points were DOR, time to response, and clinical benefit rate.

Patients were included in the trial if they had histologically or cytologically confirmed diagnosis of metastatic solid tumors, archival of fresh tumor tissue for those with molecular testing, and measurable or evaluable disease. Exclusion criteria included current participation in another trial, prior treatment with approved TRk, ROS1, or ALK inhibitors, and a history of other previous cancer that would interfere with safety or efficacy.


  1. U.S. FDA aooroves 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/3H9617V
  2. Drilon A, Siena S, Ou SI, et al. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017;7(4):400-409. doi:10.1158/2159-8290.CD-16-1237

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