Companion Diagnostic Nets European IVDR Certification for Pembrolizumab Eligibility in Gastric/GEJ Adenocarcinoma

The PD-L1 IHC 22C3 pharmDx assay (Code SK006) has received European In Vitro Diagnostic Regulation (IVDR) certification to aid in the identification of patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma patients who may be eligible for treatment with pembrolizumab (Keytruda).¹ The assay is indicated for exclusive use with the Agilent Autostainer Link 48 advanced staining solution.

PD-L1 IHC 22C3 pharmDx is a standardized immunohistochemistry (IHC) assay that contains the necessary components for 50 tests in 1 kit.² The test uses monoclonal mouse anti–PD-L1, Clone 22C3 I to detect the PD-L1 protein in paraffin-embedded tissues. Beyond the new indication in gastric/GEJ adenocarcinoma, it can be used in non–small cell lung cancer, esophageal squamous cell carcinoma, cervical cancer, head and neck squamous cell carcinoma, and triple-negative breast cancer tissues in combination with the EnVision FLEX visualization system on Autostainer Link 48.

“Immunotherapies, such as pembrolizumab, are critical for patients [with cancer],” Nina Green, vice president and general manager of the Clinical Diagnostics Division at Agilent, stated in a news release.¹ “With the current European indication expansion of PD-L1 IHC 22C3 pharmDx into gastric/GEJ adenocarcinoma, pathology laboratories can now support an even broader patient population in determining their eligibility for relevant treatment options.”

In August 2023, the European Commission (EC) approved pembrolizumab in combination with trastuzumab (Herceptin), fluoropyrimidine- and platinum-containing chemotherapy for the frontline treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric/GEJ adenocarcinoma in adults whose tumors express PD-L1 (combined positive score [CPS] ≥1).³ Additionally, pembrolizumab is approved by the EC in combination with platinum- and fluoropyrimidine-based chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic carcinoma of the esophagus or HER2-negative GEJ adenocarcinoma whose tumors have a PD-L1 CPS of at least 10.⁴

In March 2025, the FDA also granted full approval to pembrolizumab plus trastuzumab and fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with locally advanced unresectable or metastatic HER2-positive gastric/GEJ adenocarcinoma whose tumors have a PD-L1 CPS of at least 1.⁵ The regulatory decision was supported by data from the phase 3 KEYNOTE-811 trial (NCT03615326).

Findings from KEYNOTE-811 demonstrated that patients with a PD-L1 CPS of at least 1 who received pembrolizumab (n = 298) achieved a median progression-free survival (PFS) of 10.9 months (95% CI, 8.5-12.5) compared with 7.3 months (95% CI, 6.8-8.4) among those who received placebo (n = 296; HR, 0.72; 95% CI, 0.60-0.87).^5,6 Moreover, the median overall survival (OS) was 20.1 months (95% CI, 17.9-22.9) vs 15.7 months (95% CI, 13.5-18.5) in the experimental and placebo arms, respectively (HR, 0.79; 95% CI, 0.66-0.95).⁶

KEYNOTE-811 was a placebo-controlled study that enrolled patients with advanced, unresectable gastric/GEJ adenocarcinoma with HER2-positive disease per IHC as assessed by central review. In order to be eligible for the trial, patients needed to have received no prior systemic therapy in the advanced setting and have an ECOG performance status of 0 or 1.

Eligible patients were randomly assigned 1:1 to receive 200 mg of pembrolizumab or placebo once every 3 weeks in combination with trastuzumab and chemotherapy. The primary end points were OS and PFS. Overall response rate, duration of response, and safety represented secondary end points.

In terms of safety, any-grade adverse effects were reported in 99% of the investigational arm compared with 100% of the control arm. Any-grade treatment-related AEs occurred at a rate of 97% in both arms. Serious AEs (26% vs 23%), grade 3 or 4 AEs (58% vs 50%) and grade 5 AEs (1% vs 1%) were present in both arms.

References

1. Agilent receives European IVDR certification for companion diagnostic assay in gastric or gastroesophageal junction (GEJ) adenocarcinoma. News release. Agilent Technologies. April 17, 2025. Accessed April 17, 2025. https://www.agilent.com/about/newsroom/presrel/2025/17apr-ca25010.html
2. PD-L1 IHC 22C3 pharmDx overview. Agilent Technologies. Accessed April 17, 2025. https://www.agilent.com/en-us/product/pharmdx/pd-l1-ihc-22c3-pharmdx-overview
3. European Commission approves Keytruda (pembrolizumab) plus trastuzumab and chemotherapy as first-line treatment for HER2-positive advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma expressing PD-L1 (CPS ≥1). News release. Merck. August 29, 2023. Accessed April 17, 2025. https://www.merck.com/news/european-commission-approves-keytruda-pembrolizumab-plus-trastuzumab-and-chemotherapy-as-first-line-treatment-for-her2-positive-advanced-gastric-or-gastroesophageal-junction-gej-adenocarcino/
4. European Commission approves Merck’s Keytruda (pembrolizumab) plus chemotherapy for certain patients with esophageal cancer or HER2-negative gastroesophageal junction (GEJ) adenocarcinoma. News release. Merck. June 29, 2021. Accessed April 17, 2025. https://www.merck.com/news/european-commission-approves-mercks-keytruda-pembrolizumab-plus-chemotherapy-for-certain-patients-with-esophageal-cancer-or-her2-negative-gastroesophageal-junction-gej-adenocarcinom/
5. FDA approves pembrolizumab for HER2 positive gastric or gastroesophageal junction adenocarcinoma expressing PD-L1 (CPS ≥1). FDA. March 19, 2025. Accessed April 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-her2-positive-gastric-or-gastroesophageal-junction-adenocarcinoma
6. Janjigian YY, Kawazoe A, Bai Y, et al. Final overall survival for the phase III, KEYNOTE-811 study of pembrolizumab plus trastuzumab and chemotherapy for HER2+ advanced, unresectable or metastatic G/GEJ adenocarcinoma. Ann Oncol. 2024;35(suppl 2):S877-S878. doi:10.1016/j.annonc.2024.08.1466