The US regulator issued a Complete Response Letter (CRL) to MSD for its supplemental Biologics License Application (sBLA) for Keytruda or pembrolizumab in high-risk early-stage triple negative breast cancer (TNBC).
The sBLA sought backing for MSD’s checkpoint inhibitor, Keytruda, for TNBC patients in combination with chemotherapy as pre-operative treatment and then as a single agent as post-operative treatment.
The application was based on PCR data and early interim event-free survival (EFS) findings from the Phase 3 KEYNOTE-522 trial, which is continuing to evaluate for EFS.
The move by the US watchdog was not entirely unexpected, given that last month FDA’s Oncologic Drugs Advisory Committee met to discuss the submission with it indicating then that it did not see the drug as being at the approval stage for the indication in question.
That body took a unanimous vote that MSD should wait for longer-term data from KEYTRUDA-522 before requesting the FDA to approve it in that indication. The company said the next interim analysis of that data is set to occur in Q3 2021.
The company said it is reviewing the letter and will work with the FDA on its next steps.
A spokesperson for MSD told us: "We are continuing to pursue a broad clinical development program in TNBC, and we continue to study KEYTRUDA across multiple stages of triple-negative disease, including in KEYNOTE-522, KEYNOTE-355, KEYNOTE-242 and KEYLYNK-009, as well as ER+/HER2- breast cancer, and in KEYNOTE-756."
Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. It is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Positive opinion from EU regulator
Separately, MSD reported today that the European Medicines Agency (EMA) has recommended Keytruda as a monotherapy and in combination with chemotherapy for the first-line treatment of certain patients with advanced or metastatic bladder cancer, taking into account data from a phase 3 study, KEYNOTE-361.
The drug is approved in Europe for adults with advanced or metastatic cancer who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 with a Combined Positive Score of 10 or higher. That approval by the EMA’s Committee for Medicinal Products for Human Use (CHMP) was based on a single-arm study, KEYNOTE-052.
KEYNOTE-361 was conducted as part of a post-marketing commitment following the initial approval of Keytruda for these patients, said MSD. The trial did not meet its primary endpoints of progression-free survival (PFS) and overall survival (OS) for the combination of Keytruda plus chemotherapy.
Nevertheless, the CHMP concluded that the benefit-risk profile remains positive and that including data from KEYNOTE-361 in the label allows physicians to evaluate the potential benefit-risk of Keytruda on an individual basis.
Scot Ebbinghaus, vice president, clinical research, Merck (MSD) Research Laboratories. “We are pleased with today’s positive opinion by the CHMP, which fulfills our post-marketing requirement for Keytruda in these patients in the European Union and will enable continued access for patients in need of another treatment option."
MSD said it is continuing to work with regulatory authorities related to product labeling for KEYTRUDA as first-line treatment in certain patients with advanced or metastatic urothelial carcinoma. "Discussions are ongoing as additional data is generated in the course of the KEYNOTE-361 trial."
