FDA Approves Companion Diagnostic for Pembrolizumab in Esophageal/GEJ Carcinoma

The FDA has approved PD-L1 IHC 22C3 pharmDx, Code SK006, as a companion diagnostic for patients with esophageal or gastroesophageal junction (GEJ) carcinoma who may be eligible for treatment with pembrolizumab (Keytruda), according to a press release from the developer, Agilent Technologies.¹

The companion diagnostic is currently the only FDA-approved companion diagnostic indicated for patients with esophageal or GEJ carcinoma with PD-L1 expressing tumors. Notably, it is the eighth FDA approved companion diagnostic indication for PD-L1 IHC 22C3 pharmDx, Code SK006, use with pembrolizumab. These previous indications include non–small cell lung cancer, esophageal squamous cell carcinoma, cervical cancer, head and neck squamous cell carcinoma, triple-negative breast cancer, and ovarian cancers.

“With the expanded FDA approval of PD-L1 IHC 22C3 pharmDx in esophageal or GEJ carcinoma, Agilent is proud to support clinicians in identifying patients eligible for treatment with [pembrolizumab],” stated Nina Green, vice-president and general manager of Agilent’s Clinical Diagnostics Division, in the press release.¹ “This milestone reinforces Agilent’s commitment to advancing precision medicine and underscores its leadership in delivering trusted companion diagnostics that help enable treatment with anti-PD-1 therapies.”

The investigators highlighted that pembrolizumab is currently approved in combination with platinum and fluoropyrimidine-based chemotherapy for patients with metastatic or locally advanced esophageal or GEJ carcinoma who are not candidates for surgical resection or definitive chemotherapy.²

That approval was supported by efficacy data from the phase 3 KEYNOTE-590 trial (NCT03189719), which investigated pembrolizumab plus standard of care chemotherapy vs placebo plus chemotherapy in patients with esophageal or GEJ carcinoma. In that trial, the PD-L1 IHC 22C3 pharmDx kit was used to determine PD-L1 status in tumor specimens.

In 2025, 5-year follow-up data from KEYNOTE-590 were published in ESMO Open.³ With a data cutoff of July 10, 2023, and a median follow-up of 58.8 months (range, 49.2-70.6), for all randomly assigned patients, the median overall survival was 12.3 months (95% CI, 10.5-14.0) with pembrolizumab compared with 9.8 months (95% CI, 8.8-11.0) with placebo (HR, 0.72; 95% CI, 0.62-0.84). The median progression-free survival (PFS) was 6.3 months (95% CI, 6.2-7.1) vs 5.8 months (95% CI, 5.0-6.0), respectively (HR, 0.64;95% CI, 0.54-0.75).

Among patients with a PD-L1 combined positive score (CPS) of 1 or higher, the median OS was 12.7 months (95% CI, 10.6-14.3) with the pembrolizumab combination vs 9.9 months (95% CI, 8.8-11.0) with placebo (HR, 0.70; 95% CI, 0.60-0.83); the median PFS was 6.3 months (95% CI, 6.2-7.1) vs 5.7 months (95% CI, 4.6-6.0), respectively. Notably, survival outcomes by histology, PD-L1 status, and liver metastases status were consistent with findings in the overall population.

A total of 749 patients were enrolled in the trial, of whom 373 were randomly assigned to receive pembrolizumab vs 376 who received placebo. Of patients in the pembrolizumab and placebo groups, 49.9% and 52.4% had a PD-L1 CPS of 10 or higher, and 26.5% and 27.1% had adenocarcinoma while 73.5% and 72.9% had squamous-cell carcinoma.

Primary end points for that trial include OS for patients with esophageal squamous cell carcinoma with a PD-L1 CPS of 10 or higher, OS for all participants with a PD-L1 CPS of 10 or higher, and PFS for all participants with a PD-L1 CPS of 10 or higher.⁴

Regarding safety, treatment-related adverse events (TRAEs) occurred in 98.4% vs 97.3% of the pembrolizumab and placebo groups, respectively. Also, 21.1% of patients in the pembrolizumab arm and 12.4% of those in the placebo arm discontinued treatment due to TRAEs; 2.4% and 1.4% of each group died due to TRAEs.

References

1. Agilent receives FDA approval for PD-L1 IHC 22C3 pharmDx in esophageal or gastroesophageal junction (GEJ) carcinoma. News release. Agilent Therapeutics. March 26, 2026. Accessed March 27, 2026. https://tinyurl.com/yrs5dmap
2. FDA approves pembrolizumab for esophageal or GEJ carcinoma. News release. FDA. March 22, 2021. Accessed March 27, 2026. https://tinyurl.com/2hxvsd3b
3. Metges JP, Kato K, Sun JM, et al. Pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer: 5-year extended follow-up for the randomized phase III KEYNOTE-590 study. ESMO Open. 2025;10(12):105854. doi:10.1016/j.esmoop.2025.105854
4. First-line esophageal carcinoma study with pembrolizumab plus chemo vs. chemo (MK-3475-590/​KEYNOTE-590). ClinicalTrials.gov. Updated October 15, 2024. Accessed March 27, 2026. https://tinyurl.com/mt7pabry