The Oncologic Drugs Advisory Committee in a Sept. 26 meeting will discuss whether the regulator should restrict approval of checkpoint inhibitors based on PD-L1 expression levels.
The FDA is asking the Oncologic Drugs Advisory Committee to determine whether it should restrict the use of immune checkpoint inhibitors in stomach cancers. The agency announced the full-day adcomm meeting is scheduled for Sept. 26.
The regulator is seeking the committee’s guidance on using PD-L1 expression as a predictive biomarker for selecting patients that would be eligible for treatment with these drugs. The agency is also asking its external advisors to weigh in on PD-L1 levels as a basis to “restrict the approvals” of immune checkpoint inhibitors.
The Oncologic Drugs Advisory Committee (ODAC) will focus on specific stomach cancers: unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma, and metastatic or unresectable esophageal squamous cell carcinoma.
As part of the FDA’s efforts to reassess checkpoint inhibitors in stomach cancers, the ODAC will also examine currently approved treatments for these indications, including Bristol Myers Squibb’s Opdivo (nivolumab) and Yervoy (ipilimumab) and Merck’s Keytruda (pembrolizumab). The panel will also look at a new Biologics License Application for BeiGene’s Tevimbra (tislelizumab).
According to the FDA, there is mounting evidence suggesting that PD-L1 expression can potentially be “a predictive biomarker of treatment efficacy” in patients with these cancers. However, currently approved checkpoint inhibitors have broad labels and are indicated for patients regardless of PD-L1 expression, the regulator pointed out.
“Clinical trials have used different approaches to assess PD-L1 expression and different thresholds to define PD-L1 positivity,” the agency said. The adcomm meeting is meant to clarify and potentially harmonize PD-L1 recommendations in these indications.
PD-1 inhibitors have become a widely popular drug class in cancer, led by Merck’s blockbuster therapy Keytruda. These treatments work by blocking the PD-1 receptor and downstream signaling pathway, which cancer cells otherwise exploit to hide from the body’s immune system.
Clinical trials backing the approvals of PD-1 blockers have established their efficacy regardless of expression levels of PD-L1—the corresponding ligand that activates the receptor—but there is increasing evidence to support better outcomes in patients who are positive for the protein.
In June 2023, Merck presented data from its Phase III KEYNOTE-811 study showing that the anti-PD-1 treatment, when used with Herceptin (trastuzumab) and chemotherapy, can significantly improve progression-free survival (PFS) in patients with HER2-positive gastric or gastroesophageal junction adenocarcinoma.
However, a closer look at the data showed that the PFS benefit was limited only to patients whose tumors were positive for PD-L1 expression.
Given these data, Merck asked the FDA to adjust Keytruda’s label in this indication, which the FDA agreed to in November 2023.
