FDA Panel to Reassess Checkpoint Inhibitors in Two Cancers Based on Key Biomarker

The FDA’s Oncologic Drugs Advisory Committee is set to convene on Thursday to consider whether the indications for several immune checkpoint inhibitor drugs should be narrowed for two specific cancers. This review is prompted by new data regarding patient responses based on a particular biomarker, PD-L1.

Merck’s Keytruda and Bristol Myers Squibb’s Opdivo are currently approved in conjunction with chemotherapy for the initial treatment of patients with advanced HER-2 negative gastric adenocarcinoma. These approvals do not currently specify the tumor’s levels of PD-L1, a biomarker that the FDA has noted is increasingly linked to the effectiveness of these drugs.

In a briefing document provided before the meeting, the FDA expressed concerns that approvals for all patients, regardless of their PD-L1 expression levels, might not serve the best interests of those with low PD-L1 levels. The agency highlighted potential harm, including serious immune-related adverse events, for these patients, which could significantly impact their quality of life.

Bristol Myers Squibb, in its own briefing document, contended that real-world data indicate frequent PD-L1 testing in patients receiving Opdivo. The company argued that mandating the testing could restrict access to immune checkpoint inhibitors for some patients who might benefit from them.

Merck similarly opposed changes to the drug labels, arguing that comparisons between different drugs using various diagnostic tests are scientifically invalid and should not supersede the FDA’s previous evaluations based on individual study designs.

In a follow-up session on Thursday afternoon, the FDA will ask the advisory committee to deliberate on the PD-L1 issue for patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who are undergoing first-line treatment with a checkpoint inhibitor and chemotherapy.

The FDA raised concerns about the lack of observed benefits in patients with ESCC who have lower or negative PD-L1 scores, citing similar apprehensions about the risk-benefit profile of the treatment.

Merck reiterated its stance that the label for Keytruda should remain unchanged, emphasizing that the drug, when used in combination with chemotherapy, represents a significant advancement in first-line treatment for esophageal cancer patients by offering a meaningful survival benefit. Bristol Myers Squibb also reiterated its arguments from the gastric cancer review.

BeiGene, which received approval in March for tislelizumab to treat patients with unresectable or metastatic ESCC after previous systemic chemotherapy that did not include a PD-L1 inhibitor, expressed support for efforts to achieve consistency in labeling and testing across all anti-PD-1 agents.