FDA Approves FoundationOne CDx as Companion Diagnostic for Pembrolizumab in MSI-H Solid Tumors

February 21, 2022

The FDA has given the green light to the FoundationOne CDx for use as a companion diagnostic that can be leveraged to identify patients with microsatellite instability high solid tumors who may be candidates to receive and derive benefit from pembrolizumab.

The FDA has given the green light to the FoundationOne CDx for use as a companion diagnostic that can be leveraged to identify patients with microsatellite instability high (MSI-H) solid tumors who may be candidates to receive and derive benefit from pembrolizumab (Keytruda).¹

In May 2017, the FDA granted an accelerated approval to pembrolizumab for use in adult and pediatric patients with unresectable or metastatic, MSI-H or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who do not have satisfactory alternative treatment options.² The decision was based on findings from 149 patients with MSI-H or dMMR cancers in whom pembrolizumab elicited an objective response rate of 39.6% (95% CI, 31.7%-47.9%), which included a complete response rate of 7.4% and a partial response rate of 32.2%.

The in vitro diagnostic device was designed to detect substitutions, insertion, and deletion alterations, and copy number alterations in a total of 324 genes and select gene rearrangements. The test also identifies tumor mutational burden and MSI through the utilization of DNA isolated from FFPE tumor tissue specimens.

“Immunotherapy has huge promise as a potential treatment option for patients with advanced cancer; however, identifying those may benefit is complex and requires high-quality diagnostics,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated in a press release. “Not only could this approval allow more patients to benefit from [pembrolizumab], but it also underscores an important shift toward tumor-agnostic cancer care.”

Specifically, data from the KEYNOTE-016 (n = 58), KEYNOTE-164 (n = 61), KEYNOTE-012 (n = 6), KEYNOTE-028 (n = 5), and KEYNOTE-158 (n = 19) trials supported the regulatory approval of the immunotherapy. Participants were given at a dose of 200 mg every 3 weeks or 10 mg/kg every 2 weeks until progressive disease, intolerable toxicity, or a maximum of 24 months.

The median age among the 149 patients was 55 years, and 36% of patients were 65 years of age or older. Seventy-seven percent of patients were White and 56% were male. Additionally, 36% of patients had an ECOG performance status of 0 and 64% had a score of 1.

Two percent of patients had locally advanced, unresectable disease, and 98% of patients had metastatic disease. Among patients with metastatic or unresectable disease, the median number of prior therapies received was 2.

Other tumor types in which patients experienced responses with pembrolizumab included endometrial cancer (n = 5), biliary cancer (n = 3), gastric or GE junction cancer (n = 5), pancreatic cancer (n = 5), small intestinal cancer (n = 3), breast cancer (n = 2), prostate cancer (n = 1), esophageal cancer (n = 1), retroperitoneal adenocarcinoma (n = 1), and small cell lung cancer (n = 1).

Of the 149 patients, 135 had their MSI-H or dMMR tumor status determined prospectively with immunohistochemistry tests for dMMR or laboratory-developed, investigational polymerase chain reaction (PCR) tests for MSI-H status. MSI-H status for the remaining 14 patients was determined through a retrospective evaluation of 415 tumor samples using a central laboratory-developed PCR test.

IHC identified dMMR cancer in a total of 47 patients, MSI-H was identified by PCR in 60 patients, and 42 patients were identified with both tests.

Adverse effects associated with pembrolizumab include fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea. Immune-mediated side effects associated with pembrolizumab include pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.

The accelerated approval for pembrolizumab in this setting is contingent on data from a confirmatory trial.

References

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 February 21, 2022. https://bit.ly/34Xt4Un
FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. News release. FDA; May 23, 2017. Accessed February 21, 2022. https://bit.ly/2UV9yzC