FDA Approves FoundationOne CDx as a Companion Diagnostic for Entrectinib in ROS1+ and NTRK+ Cancers

The FDA has given the green light to FoundationOne CDx to identify patients with ROS1 fusion–positive non–small cell lung cancer (NSCLC) or NTRK fusion–positive cancers who might be candidates for entrectinib (Rozlytrek). Foundation Medicine said in a news release that the comprehensive genomic profiling pan-tumor tissue biopsy test is the first companion diagnostic to receive FDA approval for these diseases.¹

“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,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche. “This approval marks a significant step forward in expanding treatment options and improving outcomes for patients, particularly those with rare tumors.”

The agency based its decision on data from the phase 1 ALKA-372-001 (EudraCT 2012-000148-88), phase 1 STARTRK-1 (NCT02097810), and phase 2 STARKTRK-2 (NCT02568267) trials. Most patients received 600 mg of entrectinib once daily.

The median follow-up was 14.2 months (range 0.1-29.7) in an integrated analysis of all 3 trials assessing 74 patients with NTRK1/2/3 fusion–positive solid tumors. The overall response rate (ORR) was 63.5% (95% CI, 51.5%-74.4%), according to blinded independent central review. A total of 5 (6.8%) complete responses (CRs) were observed.²

The median duration of response (DOR) was 12.9 months (95% CI, 9.3-not evaluable [NE]). The median progression-free survival was 11.2 months (95% CI, 8.0-15.7) with a median overall survival of 23.9 months (16.0-NE).

In patients who did not have investigator-assessed central nervous system (CNS) disease (n = 55) at baseline, the ORR was 65.5% (95% CI, 51.4%-77.8%). The median DOR was 12.9 months (95% CI, 9.30-NE) among patients who responded to treatment. In patients with baseline CNS disease (n = 19), the ORR was 57.9% (95% CI, 33.5%-79.8%) with a median DOR in responders of 6.0 months (95% CI, 4.2-NE).

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

Twenty-four patients in the study received prior immunotherapy. The ORR was 70.8% (95% CI 48.9%-87.4%) in that subgroup. In patients with investigator-assessed CNS metastases at baseline, the ORR was 62.5% (95% CI, 48.6%-75.1%).

This approval is contingent on outcomes from a study further assessing the FoundationOne CDx. Foundation Medicine will conduct a post-approval study using the Flatiron Health-Foundation Medicine’s Clinico-Genomic Database (CGDB) to further demonstrate FoundationOne CDx’s ability to identify patients with ROS1 fusion–mutated NSCLC who could be eligible for entrectinib treatment. The CGDB database currently contains more than 100,000 linked genomic profiles and links outcomes data from Flatiron’s network of oncology clinics and genomic data from Foundation Medicine’s comprehensive genomic profiling assays.

The FDA approved FoundationOne CDx in February 2022 as a companion diagnostic to identify patients with microsatellite instability–high (MSI-H) solid tumors who may be candidates to receive and derive benefit from pembrolizumab (Keytruda).⁴

The agency first approved the tissue-based biopsy in November 2017. FoundationOne CDx is currently approved as a companion diagnostic for 25 indications and 3 group claims across 30 targeted therapies.¹

References

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/3NZbd00
2. Rolfo CD, De Braud FG, Doebele RC, et al. Efficacy and safety of entrectinib in patients (pts) with NTRK fusion-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
3. Krebs MG, De Braud F, Siena S, et al. Efficacy and safety of entrectinib in locally advanced/metastatic ROS1 fusion-positive NSCLC: an updated integrated analysis. Ann Oncol. 2020;31:S831-S833. doi:10.1016/j.annonc.2020.08.1601
4. US FDA approves FoundationOne CDx as a companion diagnostic for KEYTRUDA (pembrolizumab) to identify patients with microsatellite instability-high (MSI-H) solid tumors. News release. Foundation Medicine, Inc.; February 21, 2022. Accessed June 9, 2022. https://bit.ly/34Xt4Un