FDA Approves Pembrolizumab CDx for MSI-H Solid Tumors


The FDA has approved FoundationOne CDx as a companion diagnostic to pembrolizumab for patients with microsatellite instability high solid tumors.

The FoundationOne CDx has been approved by the FDA for use as a companion diagnostic to identify patients with microsatellite instability high (MSI-H) solid tumors who may be candidates to receive and pembrolizumab (Keytruda) and benefit from it.1

Pembrolizumab was previously granted approval by the FDA in 2017 for the treatment of adult and pediatric patients with MSI-H or mismatch repair deficient solid tumors that have progressed following prior treatment and who do not have satisfactory alternative treatment options.2 This decision was based on data from the 149 patients with MSI-H or dMMR cancers enrolled across 5 single-arm clinical trials.

“Immunotherapy has huge promise as a potential treatment option for patients with advanced cancer; however, identifying those that 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.”

FoundationOne CDx is an in vitro diagnostic device made to detect substitutions, insertion/deletion alterations, and copy number alterations in a total of 324 genes as well as select gene rearrangements. It uses formalin-fixed, paraffin-embedded tumor tissue specimens to do so.

Findings from KEYNOTE-016 (NCT01876511), KEYNOTE-164 (NCT02460198), KEYNOTE-012 (NCT01848834), KEYNOTE-028 (NCT02054806), and KEYNOTE-158 (NCT02628067) supported the accelerated approval of this immunotherapy. During these studies, participants were given pembrolizumab at a dose of 200 mg every 3 weeks or 10 mg/kg every 2 weeks until a maximum of 24 months, progressive disease, or intolerable toxicity.

Among the 149 patients enrolled across the trials, the median age was 55 years and patients aged 65 years or older made up 36%. Additionally, 77% of patients were White, 56% were male, 36% had an ECOG performance status of 0 and 64% had a score of 1. Ninety patients had colorectal cancer (CRC) and the remaining 59 patients had 1 of 14 other tumor types.

With pembrolizumab, the objective response rate (ORR) was 39.6% (95% CI, 31.7-47.9). This included 11 (7.4%) complete responses (CRs) and 48 (32.2%) partial responses (PRs). In patients with colorectal cancer, The ORR was 36% in patients with CRC and 46% in patients with other tumor types. The median duration of response had not been reached (range, 1.6+ months to 22.7+ months). For patients who responded to pembrolizumab, 78% reported responses that lasted for at least 6 months.

Beyond CRC, other tumor types in which patients had responses 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).

Locally advanced, unresectable disease was found in 2% of the patients while 98% had metastatic disease. The median number of prior therapies received was 2 for patients with metastatic or unresectable disease.

Of the 149 patients enrolled, 135 had their MSI-H or dMMR tumor status determined with the use of immunohistochemistry tests for dMMR or laboratory-developed, investigational polymerase chain reaction (PCR) tests for MSI-H status while the remaining 14 patients’ MSI-H status 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.

Some common 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.

Based on data from prior trials, pembrolizumab has been granted accelerated approval in this setting.

  1. 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 22, 2022. https://bit.ly/34Xt4Un
  2. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. News release. FDA; May 23, 2017. Accessed February 22, 2022. https://bit.ly/2UV9yzC

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