PD-L1 IHC 22C3 pharmDx Gets Green Light From FDA for Determining Pembrolizumab Eligibility in Gastric/GEJ Adenocarcinoma

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The FDA has approved the PD-L1 IHC 22C3 pharmDx diagnostic tool to aid clinicians in identifying patients with gastric or gastroesophageal junction adenocarcinoma who may be eligible for treatment with the PD-1 inhibitor pembrolizumab.

The FDA has approved the PD-L1 IHC 22C3 pharmDx diagnostic tool to aid clinicians in identifying patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma who may be eligible for treatment with the PD-1 inhibitor pembrolizumab (Keytruda), according to an announcement from Agilent Technologies, Inc, the manufacturer of the tool.¹

PD-L1 IHC 22C3 pharmDx became the lone companion diagnostic capable of identifying patients with gastric or GEJ adenocarcinoma who are suitable for treatment with pembrolizumab plus chemotherapy, trastuzumab (Herceptin), and fluoropyrimidine that is approved by the FDA. The tool was developed as a companion diagnostic for pembrolizumab and is now approved by the FDA in 6 cancer types.¹

“PD-L1 expression is a critical biomarker for response to anti–PD-1 therapies such as pembrolizumab,” Lou Welebob, vice president and general manager of Agilent’s Pathology Division, said in a news release. “This endorsement underscores Agilent’s leadership in the development of companion diagnostics for groundbreaking anti–PD-1 therapies.”¹

On May 5, 2021, the FDA first granted accelerated approval to pembrolizumab in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy for the frontline treatment of patients with advanced unresectable or metastatic HER2-positive gastric or GEJ adenocarcinoma.² However, on November 7, 2023, the FDA updated the indication to restrict the use of the combination to patients whose tumors express PD-L1 (combined positive score ≥ 1) as determined by an FDA-approved test. The FDA noted that the updated indication remains approved under accelerated approval regulations.³

Both indications were supported by findings from the phase 3 KEYNOTE-811 trial (NCT03615326), which evaluated pembrolizumab 200 mg every 3 weeks or placebo, both in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy in patients HER2-positive advanced gastric or GEJ adenocarcinoma who had not previously received systemic therapy for metastatic disease. In the multicenter, double-blinded study, the PD-L1 IHC 22C3 pharmDx tool was used to determine PD-L1 status. Progression-free survival (PFS) per RECIST v1.1 criteria by blinded independent central review and overall survival (OS) represented the coprimary end points.⁴

Findings from the prespecified interim analysis that supported the accelerated approval showed that patients in the pembrolizumab arm (n = 133) achieved an objective response rate of 74% (95% CI, 66%-82%) compared with 52% (95% CI, 43%-61%) in the placebo arm (n = 131), including respective complete response rates of 11% and 3.1% (1-sided P < .0001). The median duration of response (DOR) was 10.6 months (range, 1.1+ to 16.5+) vs 9.5 (range, 1.4+ to 15.4+), respectively, with 65% and 53% of patients, respectively, achieving a DOR of at least 6 months.Data from a recent interim analysis showed that in the full study population (n = 698), patients with a PD-L1 CPS of less than 1 (n = 104) experienced a hazard ratio of 1.03 (95% CI, 0.65-1.64) for PFS and 1.41 (95% CI, 0.90-2.20) for OS.⁴

Outside of gastric and GEJ adenocarcinoma, PD-L1 IHC 22C3 pharmDx can aid clinicians in identifying patients with non–small cell lung cancer, esophageal squamous cell carcinoma, cervical cancer, head and neck squamous cell carcinoma, and triple-negative breast cancer who may derive benefit from pembrolizumab.¹