FDA Approves PD-L1 IHC 28-8 pharmDx as Companion Diagnostic for Nivolumab Plus Ipilimumab in NSCLC

The FDA has approved PD-L1 IHC 28-8 pharmDx for use as a companion diagnostic to identify patients with metastatic non—small cell lung cancer (NSCLC) with PD-L1 tumor expression ≥1%, making them eligible for frontline treatment with nivolumab (Opdivo) plus ipilimumab (Yervoy), if their tumors also do not have EGFR or ALK genomic tumor aberrations.¹

The FDA recently approved the nivolumab/ipilimumab combination for use in this setting in patients whose PD-L1 status has been determined by an FDA-approved test.

“The expanded use of PD-L1 IHC 28-8 pharmDx will give physicians in the USA critical information to inform first-line treatment decisions for patients with metastatic non—small cell lung cancer,” Sam Raha, president of Agilent's Diagnostics and Genomics Group, stated in a press release.

The PD-L1 IHC 28-8 pharmDx was created in 2016 through the collaborated efforts of Agilent and Bristol Myers Squibb, the manufacturer of nivolumab and ipilimumab. According to Agilent, the test was previously approved as “a complementary in vitro diagnostic for nonsquamous non—small cell lung cancer, as well as other forms of cancer, including squamous cell carcinoma of the head and neck, and urothelial carcinoma.”

The frontline approval of nivolumab/ipilimumab was based on findings from part 1 of the phase 3 CheckMate-227 trial. In the multi-part, open-label, phase 3 CheckMate-227 trial, investigators evaluated first-line nivolumab-based regimens versus platinum-doublet chemotherapy in patients with advanced NSCLC across nonsquamous and squamous histologies. In part 1a of the study, nivolumab plus low-dose ipilimumab or nivolumab alone was compared with chemotherapy in patients with PD-L1—positive NSCLC. In part 1b, nivolumab/low-dose ipilimumab plus chemotherapy versus chemotherapy alone was evaluated in patients whose tumors do not express PD-L1.

The results showed that nivolumab combined with ipilimumab demonstrated a significant improvement in overall survival (OS) compared with chemotherapy alone in patients with previously untreated NSCLC.^2,3 In a cohort of patients with PD-L1 expression ≥1%, the median OS with nivolumab and ipilimumab compared with chemotherapy was 17.1 months and 14.9 months, respectively (HR, 0.79; 95% CI, 0.67-0.94; P = .0066). Moreover, the median OS was 17.1 months with the combination and 14.9 months with chemotherapy in all randomized patients, regardless of PD-L1 expression status (HR, 0.73; 95% CI, 0.64-0.84).

With a minimum follow up of 28.3 months, the confirmed overall response rate per blinded independent central review was 36% with nivolumab/ipilimumab, compared with 30% in the chemotherapy arm. The median duration of response by blinded independent central review was 23.2 months, 15.5 months, and 6.2 months for nivolumab/ipilimumab, nivolumab, and chemotherapy, respectively. The rates of patients in response at 1 year were 64%, 63%, and 28%, respectively; the rates of those in response at 2 years were 49%, 40%, and 11%, respectively.

References

1. Agilent PD-L1 Assay Receives FDA Approval for Use as a Companion Diagnostic. Published May 18, 2020. https://www.businesswire.com/news/home/20200518005141/en/Agilent-PD-L1-Assay-Receives-FDA-Approval-Companion. Accessed May 18, 2020.
2. Peters S, Ramalingam S, Paz-Ares L, et al. Nivolumab + low-dose ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non—small cell lung cancer: CheckMate-227 part 1 final analysis. Presented at: 2019 ESMO Congress; September 27 to October 1, 2019; Barcelona, Spain. Abstract LBA4.
3. Hellmann MD, Paz-Ares L, Carbo RB, et al. Nivolumab plus ipilimumab in advanced non—small-cell lung cancer [published online September 28, 2019]. N Eng J Med. doi: 10.1056/NEJMoa1910231