PD-L1 IHC 22C3 pharmDX Assay Approval Expanded by FDA in NSCLC

The approval of the PD-L1 22C3 pharmDX assay has been expanded by the FDA to be used as a companion diagnostic for identifying more patients with stage III or metastatic non–small cell lung cancer who can undergo frontline treatment with pembrolizumab.

Sam Raha

The approval of the PD-L1 22C3 pharmDX assay has been expanded by the FDA to be used as a companion diagnostic for identifying more patients with stage III or metastatic non—small cell lung cancer (NSCLC) who can undergo frontline treatment with pembrolizumab (Keytruda).1

This update coincides with the FDA's approval of frontline single-agent pembroilzumab as a treatment for patinets with stage III NSCLC who are not candidates for surgery or definitive chemoradiation, or metastatic NSCLC, with a PD-L1 expression (tumor proportion score [TPS]) level of ≥1% and do not harbor EGFRor ALKaberrations.2

"Anti—PD-1 therapies are a promising treatment class for many cancer types, and PD-L1 testing provides key information to physicians managing stage III or metastatic NSCLC patients," said Sam Raha, president, Agilent's Diagnostics and Genomics Group, the developer of the assay. "The updated FDA approval of PD-L1 IHC 22C3 pharmDx broadens the scope of patients that can be identified for first-line treatment with Keytruda and offers new hope to the many patients diagnosed with stage III or metastatic NSCLC. By expanding the use of PD-L1 IHC 22C3 pharmDx, Agilent strives to continue our legacy of pioneering companion diagnostics to support the launch of landmark therapies."

The updated approval will allow pathologists to identify this larger population of previously untreated patients with NSCLC who are now eligible for treatment with pembrolizumab, Agilent Technologies Inc., noted in a press release. The PD-L1 IHC 22C3 pharmDx, which is developed in partnership with Merck, the manufacturer of pembrolizumab, is the sole companion diagnostic that is clinically validated and approved to identify patients with NSCLC who are eligible to receive the PD-1 inhibitor.

The assay is also used by physicians to identify patients with cervical cancer, gastric or gastroesophageal junction adenocarcinoma, and urothelial carcinoma who are eligible for pembrolizumab monotherapy. In these malignancies, PD-L1 expression is deciphered with the use of Combined Positive Score compared with TPS in NSCLC tissues.

The April 2019 decision for the expanded pembrolizumab approval was based on results from the phase III KEYNOTE-042 trial, which showed that frontline pembrolizumab led to a median overall survival (OS) of 16.7 months versus 12.1 months with standard chemotherapy in patients with advanced or metastatic NSCLC and TPS ≥1% (HR, 0.81; 95% CI, 0.71-0.93;P= .0036).3Findings of an exploratory analysis, which examined all patients with PD-L1 TPS of 1% to 49%, showed that the median OS was 13.4 months and 12.1 months with pembrolizumab and chemotherapy, respectively (HR, 0.92; 95% CI, 0.77-1.11).

The initial FDA action date on the supplemental biologics license application (sBLA) for pembrolizumab for use in this setting was January 11, 2019. However, in December 2018, the FDA extended the review period for the sBLA, making the new date April 11, 2019. Merck previously reported in a press release that the extension would allow sufficient time for the FDA to review supplementary information the company had submitted for the application.


  1. Agilent Receives an Expanded FDA Approval for its Companion Diagnostic in NSCLC. Agilent Therapeutics. Published April 16, 2019. https://bit.ly/2PnPAK5. Accessed April 17, 2019.
  2. FDA expands pembrolizumab indication for first-line treatment of NSCLC (TPS ≥1%). FDA. Published April 11, 2019. https://bit.ly/2Ut6Cfv. Accessed April 11, 2019.
  3. Lopes G, Wu YL, Kudaba I, et al. Pembrolizumab (pembro) versus platinum-based chemotherapy (chemo) as first-line therapy for advanced/metastatic NSCLC with a PD-L1 tumor proportion score (TPS) ≥ 1%: open-label, phase 3 KEYNOTE-042 study. Presented at: 2018 ASCO Annual Meeting; June 1-5; Chicago. Abstract LBA4.