The FDA’s Oncologic Drugs Advisory Committee will meet Thursday to discuss whether several immune checkpoint inhibitor drugs should come with narrower indications in two cancers, based on emerging data about how patients respond based on a biomarker.
Merck’s Keytruda and Bristol Myers Squibb’s Opdivo are both approved in combination with chemotherapy as a first-line treatment of patients with advanced HER-2 negative gastric adenocarcinoma. Those approvals don’t currently take a position on a tumor’s levels of PD-L1, a biomarker that, according to the FDA, is increasingly shown to be associated with responses to the drugs.
In a briefing document issued ahead of the meeting, the agency said that “approvals for all randomized patients may not be in the best interest of patients with tumors with low PD-L1 expression” and that giving the drugs to patients with low or no PD-L1 expression “has the potential for harm including serious immune related adverse events on top of a malignancy that can markedly affect a patient’s quality of life.”
Bristol Myers, in its own briefing document, said that real-world data show that PD-L1 testing already occurs frequently in patients treated with Opdivo. The company argued that requiring the testing “may result in some patients who might benefit from [immune checkpoint inhibitors] not having access to them.”
Merck likewise argued that the agency shouldn’t change the labels. “Cross-study comparisons with other drugs using different diagnostic tests are not scientifically valid and should not override FDA’s previous analysis of results based on design of individual studies,” the company said.
In a foll0w-up session Thursday afternoon, the FDA will ask the advisory committee to examine the same PD-L1 issue for patients with with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who are getting first-line treatment with a checkpoint inhibitor and chemo.
“FDA is concerned with the lack of benefit observed across patients with ESCC who have lower (or negative) PD-L1 scores,” the agency wrote ahead of the meeting, citing similar concerns about the risk-benefit profile of treatment.
Merck again argued the label should remain unchanged, saying that Keytruda in combo with chemo is “a paradigm-changing [first-line] treatment option that offers a clinically meaningful survival benefit for [first-line] esophageal cancer patients.” Bristol Myers also echoed its arguments from the gastric cancer review.
BeiGene, which won approval in March for tislelizumab to treat patients with unresectable or metastatic ESCC after prior systemic chemotherapy that did not include a PD-L1 inhibitor, said it “supports efforts in gaining consistency in labeling and testing across the class of anti-PD-1 agents.”