FDA Requests More Data from Merck on Keytruda for Breast Cancer
FDA officials stated that further data is needed from Merck’s Phase 3 trial of its monoclonal antibody, Keytruda, before a regulatory decision is made.
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By - Merck recently announced that FDA issued a Complete Response Letter (CRL) in regards to Merck’s supplemental Biologics License Application (sBLA) seeking approval for its monoclonal antibody, Keytruda.
In the CRL, FDA’s Oncologic Drugs Advisory Committee voted 10 to 0 that a regulatory decision about Keytruda should be deferred until further data are available from its Phase 3 clinical trial, KEYNOTE-522.
The agency’s decision was based on pathological complete response (pCR) data and early interim event-free survival (EFS) findings from the trial, KEYNOTE-522.
Keytruda is an anti-PD-1 therapy for the treatment of patients with high-risk early-stage triple-negative breast cancer in combination with chemotherapy as pre-operative treatment, Merck explained.
At the end of September, results from the clinical trial KEYNOTE-522 were published in the New England Journal of Medicine.
In the trial, researchers randomly assigned patients with previously untreated stage 2 or stage 3 triple-negative breast cancer to receive pre-operative therapy with four cycles of Keytruda at a dose of 200 milligrams every three weeks.
This therapy was combined with two chemotherapy medications—paclitaxel and carboplatin.
The groups then received an additional four cycles of pembrolizymab or a placebo. The groups also received chemotherapies doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide.
Among the first 602 patients who underwent randomization, 64.8 percent in the pembrolizumab chemotherapy group and 51.2 percent of patients in the placebo-chemotherapy group elicited complete response.
After a median follow-up of 15.5 months, 7.4 percent of patients in the pembrolizumab-chemotherapy group and 11.8 percent in the placebo-chemotherapy group had disease progression that precluded definitive surgery, had local or distant recurrence or a second primary tumor, or died from any cause.
Researchers concluded that “among patients with early triple-negative breast cancer, the percentage with complete response was significantly higher among those who received pembrolizumab plus pre-operative chemotherapy than among those who received placebo plus pre-operative chemotherapy.”
FDA’s CRL does not impact any currently approved indications for Keytruda, the announcement highlighted.
This includes the indication for Keytruda in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple negative breast cancer whose tumors express PD-L1, as determined by an FDA-approved test.
Currently, FDA has approved Keytruda for the treatment of melanoma, non-small cell lung cancer, small cell lung cancer, head and neck squamous cell carcinoma, classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, urothelial carcinoma.
Merck stated that it is reviewing the recent CRL and will discuss next steps with FDA.
One day after receiving the CRL, Merck announced that the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for expanded approval of Keytruda in certain patients with relapsed or refractory Hodgkin lymphoma.
The CHMP, part of the European Medicines Agency (EMA), recommended that Keytruda be updated to include data from Merck’s Phase 3, open-label trial, KEYNOTE-361.
In the trial, researchers evaluated Keytruda as a monotherapy and in combination with chemotherapy for the first-line treatment of certain patients with advanced or metastatic urothelial carcinoma.
CHMP based its approval on a single-arm study, KEYNOTE-052. Additionally, KEYNOTE-361 was conducted as part of a post-marketing commitment following the initial approval of Keytruda for these patients.
In Europe, Keytruda is already approved for the treatment of adult patients with advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy and whose tumors expressed PD-L1 with a combined positive source, Merck said.
Merck has the industry’s largest immuno-oncology clinical research program. Currently, there are over 1,400 trials studying Keytruda across a wide variety of cancers and treatment settings.
The Keytruda clinical program aims to understand the role of the drug across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda.
