FDA Approves Pembrolizumab Companion Diagnostic for Frontline PD-L1+ NSCLC

"We are delighted to add the first FDA approval of this important companion diagnostic on Dako Omnis."

The FDA granted approval for PD-L1 IHC 22C3 pharmDx as a companion diagnostic (CDx) as an identifier of patients with non–small cell lung cancer who are eligible for frontline treatment with pembrolizumab (Keytruda) monotherapy. The CDx will identify these patients on the Dako Omnis platform for immunohistochemistry (IHC) and in situ hybridization, according to a press release from Agilent Technologies, Inc.1

PD-L1 IHC 22C3 pharmDx previously underwent clinical validation to determine its accuracyfor use in the NSCLC space.

“We are delighted to add the first FDA approval of this important companion diagnostic on Dako Omnis,” Simon Østergaard, Agilent vice president, and general manager of the company’s pathology division, said in a statement. “Our PD-L1 IHC 22C3 pharmDx assay is used by thousands of laboratories around the globe, and now customers in the US can add PD-L1 to their routine IHC workflow on Dako Omnis.”

Pembrolizumab was approved for an expanded indication by the FDA in April 2019 for the first-line treatment of patients with stage III non–small cell lung cancer who are not candidates for surgical resection or definitive chemoradiation or metastatic NSCLC, have no EGFR or ALK genomic aberrations, and express PD-L1 (Tumor Proportion Score [TPS] ≥1%) as determined by an FDA-approved test. The expansion was based on data from the phase III KEYNOTE-042 study (NCT02220894), which randomized 1274 patients 1:1 to receive pembrolizumab 200 mg or the investigator’s choice of a carboplatin-containing regimen in combination with either pemetrexed or paclitaxel.2

The result showed that in the subset of patients with TPS ≥1%, the median overall survival (OS) was 16.7 months with pembrolizumab versus 12.1 months with chemotherapy (HR, 0.81; 95% CI, 0.71-0.93; P = .0036). In the subset of patients with TPS ≥ 20%, the median OS was 17.7 months with pembrolizumab compared with 13.0 months in the chemotherapy arms (HR, 0.77; 95% CI, 0.64-0.92; P = .004). The subgroup of patients with TPS ≥50% achieved a median OS of 20.0 months with pembrolizumab versus 12/2 months with chemotherapy (HR, 0.69; 95% CI, 0.56-0.85; P = .0006). No significant differences in progression-free survival (PFS) or overall response rate (ORR) were observed between the 2 study arms.

The most common adverse events (AEs) seen with pembrolizumab in KEYNOTE-042 was fatigue, decreased appetite, dyspnea, cough, rash, constipation, diarrhea, hypothyroidism, pneumonia, pyrexia, and weight loss, which occurred in 10% of patients.

Patients with histologically or cytologically confirmed advanced or metastatic NSCLC, with PD-L1-positive tumors, measurable disease, life expectancy of at least 3 months, an ECOG performance status of 0 to 1, and adequate organ function were eligible to enroll in the study.

The primary end point of the study is OS, and the secondary endpoints are PFS, ORR, and safety.

PD-L1 expression in the KEYNOTE-042 study was determined with the PD-L1 IHC 22C3 pharmDx Kit.


1. Agilent receives FDA approval for pd-l1 companion diagnostic on Dako Omnis [news release]. Santa Clara, California: Agilent Technologies, Inc; April 23, 2020. https://bit.ly/3cIU3kR. Accessed April 23, 2020.

2. FDA expands pembrolizumab indication for first-line treatment of NSCLC (TPS ≥1%) [news release]. Published on FDA website. https://bit.ly/2RZe7av. Accessed April 23, 2020.