publication date: Nov. 20, 2020
Drugs & Targets
Keytruda receives accelerated approval from FDA for locally recurrent, unresectable or metastatic TNBC
Keytruda (pembrolizumab) received accelerated approval from FDA in combination with chemotherapy for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer whose tumors express PD-L1 (CPS ≥10) as determined by an FDA approved test.
Keytruda is sponsored by Merck.
FDA also approved the PD-L1 IHC 22C3 pharmDx (sponsored by Dako North America Inc.) as a companion diagnostic for selecting patients with TNBC for pembrolizumab.
Approval was based on KEYNOTE-355 (NCT02819518), a multicenter, double-blind, randomized, placebo-controlled trial in patients with locally recurrent unresectable or metastatic TNBC, who had not been previously treated with chemotherapy in the metastatic setting. Patients were randomized (2:1) to receive pembrolizumab 200 mg on day one every every weeks or placebo in combination with different chemotherapy treatments (paclitaxel protein-bound, or paclitaxel, or gemcitabine plus carboplatin) via intravenous infusion.
The main efficacy outcome measure was progression-free survival as assessed by blinded independent review according to RECIST 1.1, tested in the subgroup of patients with CPS ≥10. Median PFS was 9.7 months (95% CI: 7.6, 11.3) in the pembrolizumab plus chemotherapy arm and 5.6 months (95% CI:5.3, 7.5) in the placebo arm (HR 0.65; 95% CI: 0.49, 0.86; one-sided p-value=0.0012).
FDA issues draft guidance to provide important considerations in cross labeling of oncology drugs
FDA has issued a Draft Guidance for comment describing the agency’s proposed recommendations for including relevant information about oncology drug labels that have been approved for use in combination drug regimens.
Cross-labeling is the inclusion of information in product labeling of two or more oncology drugs approved in a combination regimen for a specific indication. The intent is to provide information in product labeling for the drugs used in a combination regimen that are complementary and consistent and not to include all of the same information in labeling for each drug in the combination regimen.
“Oncology drug applications to the FDA often add investigational drugs to current regimens to create new combination regimens with greater efficacy or safety. Sponsors have traditionally not requested cross-labeling—making changes to the labeling of a previously approved drug that describes how to use that drug in a new regimen,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research, said in a statement.
“However, recently we’ve seen an increase in the number of applications that have proposed cross-labeling for oncology drug combination regimens,” he said.
The draft guidance includes procedures for cross-labeling application submissions and considerations for selected sections in the “Full Prescribing Information” part of the drug label.
“We are issuing today’s draft guidance to serve as a starting point for discussions between the FDA and sponsors of oncology drugs, as well as the medical and academic communities, and the public on including relevant information in labeling for oncology drugs approved for use in a combination regimen,” Pazdur said. “Cross-labeling can provide clear, consistent and accessible information to guide the safe and effective use of cross-labeled drugs in an oncology treatment regimen.”
CDER and CBER to increase Emergency Use Authorization transparency
The Center for Drug Evaluation and Research and the Center for Biologics Evaluation and Research at FDA plan to take additional steps to increase transparency regarding CDER and CBER’s review of the scientific information supporting the issuance of or revisions to an emergency use authorizations.
The goal is to be as transparent as possible under the law about the scientific basis for recommending that a drug or biological product be authorized for emergency use under the Federal Food, Drug and Cosmetic Act.
In the future, when a CDER-regulated or CBER-regulated product is authorized for emergency use, FDA intends to make public to the extent appropriate and permitted by law the center’s review of the scientific data and information supporting our recommendation to issue, revise, or revoke the EUA.
When an EUA is revised, FDA also intends to make public to the extent permitted by law the center’s reviews of the scientific data and information supporting our recommendations to revise the EUA.
Agendia and Paige collaborate on breast cancer research
Agendia Inc. and Paige, are collaborating to co-development treatment planning tools that integrate the cloud-based Paige Platform with genomic information from Agendia’s proprietary MammaPrint and BluePrint diagnostic tests for patients with breast cancer.
These products aim to enable faster access to predictive and prognostic information, from diagnosis and early intervention to metastatic treatment planning.
“Our goal is to provide same-day turnaround in most cases, enable earlier intervention, preserve limited biopsy or surgical tissue specimens, and extend key benefits to physicians and their patients with access to testing in countries where tissue ‘send out’ is not allowed,” Agendia Chief Executive Officer Mark Straley said in a statement.
The initial focus of the collaboration will be the development of digital tests for early treatment planning where genomic testing has played an essential role in determining recurrence risk and tumor biology as doctors and their patients make decisions about the path ahead.
Beyond early intervention, AI-derived biomarkers will be used to augment genomic testing in the metastatic setting, where therapeutic options can add to the complexity of treatment planning.