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The FDA has accepted a new supplemental biologics license application that is seeking the approval of pembrolizumab for use as a monotherapy in patients with advanced endometrial carcinoma that is microsatellite instability–high or mismatch repair deficient, who have progressed after systemic therapy in any setting and are not eligible for curative surgery or radiation.
The FDA has accepted a new supplemental biologics license application (sBLA) that is seeking the approval of pembrolizumab (Keytruda) for use as a monotherapy in patients with advanced endometrial carcinoma that is microsatellite instability–high (MSI-H) or mismatch repair deficient (dMMR), who have progressed after systemic therapy in any setting and are not eligible for curative surgery or radiation.1
The application is supported by findings pertaining to overall response in cohorts D and K of the phase 2 KEYNOTE-158 trial (NCT02628067), which will be shared during the 2021 ESMO Congress.
The regulatory agency is slated to decide on the sBLA by March 28, 2022, under the Prescription Drug User Fee Act.
“The FDA’s acceptance of our application adds to our momentum of advancing new treatment options to address the most challenging cancers facing women,” Scot W. Ebbinghaus, MD, vice president of clinical research at Merck Research Laboratories, stated in a press release. “[Pembrolizumab] monotherapy is already playing a role of the treatment of certain patients with advanced endometrial carcinoma through the tumor agnostic MSI-H indication which received accelerated approval 4 years ago. We look forward to sharing the latest results from KEYNOTE-158, including updated data for [pembrolizumab] in certain types of MSI-H/dMMR advanced endometrial carcinoma, at the ESMO Congress in September.”
On May 2017, the FDA granted an accelerated approval to pembrolizumab for use in adult and pediatric patients with unresectable or metastatic, MSI-H or dMMR solid tumors that have progressed following previous treatment and who have no acceptable alternative treatment options, as well as for those with MSI-H or dMMR colorectal cancer (CRC) after progression on fluoropyrimidine, oxaliplatin, and irinotecan.2
The decision was based on data from all cohorts enrolled to KEYNOTE-158, which had comprised 233 patients. The objective response rate (ORR) with the immunotherapy was 34.3% (95% CI, 28.3%-40.8%), with 77.6% of patients experiencing a duration of response (DOR) that was 24 months or longer.3 The median progression-free survival (PFS) in these patients was 4.1 months (95% CI, 2.4-.4.9), and the median overall survival (OS) was 23.5 months (95% CI, 12.5–not reached).
Data from an analysis of a higher number of patients enrolled to cohort K of KEYNOTE-158, with an additional 22.0 months of follow-up, were presented during the 2021 ASCO Annual Meeting. Cohort K included patients with any advanced solid tumor that was MSI-H, excluding CRC.
Patients had to have progressed on, or show intolerance to, 1 or more lines of standard therapy for unresectable and/or metastatic disease. Moreover, patients had to have measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1.
A total of 351 patients received intravenous pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 treatment cycles.
The primary end point of the research was ORR per RECIST v1.1 criteria and blinded independent central review (BICR), and key secondary end points comprised DOR and PFS per RECIST criteria and BICR, as well as OS and safety.
Updated data showed that in 321 patients, the ORR was 30.8% (95% CI, 25.8%-36.2%) with the immunotherapy; this included a complete response rate of 8.4%, a partial response rate of 22.4%, and a stable disease rate of 19.0%.
In this population, the median PFS was 3.5 months (95% CI, 2.3-4.2) with pembrolizumab, and the median OS was 20.1 months (95% CI, 14.1-27.1). The 36-month PFS and OS rates in this group were 24.0% and 39.1%, respectively.
Regarding safety, treatment-related adverse effects (TRAEs) were experienced by 64.7% of a total of 351 patients; 12.0% of these effects were grade 3 to 5 in severity. Three patients experienced TRAEs that resulted in death, and 23 patients had treatment-related toxicities that resulted in discontinuation.
The AEs that were most frequently reported with pembrolizumab included pruritus (14.5%), fatigue (12.3%), diarrhea (11.7%), arthralgia (9.4%), asthenia (9.1%), hypothyroidism (8.8%), rash (7.1%), and nausea (6.3%).