KEYNOTE-355 Meets a Coprimary End Point for Treatment of Patients with mTNBC

February 12, 2020

First-line treatment with pembrolizumab in combination with chemotherapy showed a statistically significant and clinically meaningful improvement in progression-free survival compared with chemotherapy alone in patients with metastatic triple-negative breast cancer who had PD-L1 expression in their tumors, meeting one of the coprimary end points of the phase III KEYNOTE-355 trial, according to the results of an interim analysis reported in a press release from Merck.

First-line treatment with pembrolizumab (Keytruda) in combination with chemotherapy showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with chemotherapy alone in patients with metastatic triple-negative breast cancer (mTNBC) who had PD-L1 expression in their tumors, meeting one of the coprimary end points of the phase III KEYNOTE-355 trial (NCT02819518), according to the results of an interim analysis reported in a press release from Merck.

“Triple-negative breast cancer is an aggressive malignancy. It is encouraging that Keytruda in combination with chemotherapy has now demonstrated positive results as both a first-line treatment in the metastatic setting with this trial, and as neoadjuvant therapy in the KEYNOTE-522 trial,” Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, said in a statement.

There were no new safety signals observed with pembrolizumab in the study and the trial will continue without changes based on recommendations given by the Data Monitoring Committee that analyzed the findings.

KEYNOTE-355 is a randomized, double-blind, 2-part study. During part 1, 30 patients were randomized to 1 of 3 regimens. All patients received intravenous (IV) pembrolizumab 200 mg on day 1 of each 21-day cycle plus either nab-paclitaxel (Abraxane) 100 mg/m2IV on Days 1, 8, and 15 of each 28-day cycle; paclitaxel 90 mg/m2IV on Days 1, 8, and 15 of each 28-day cycle; or gemcitabine 1000 mg/m2and carboplatin area under the curve 2 on days 1 and 8 of each 21-day cycle.

Part 1 of KEYNOTE-355 primarily evaluated the toxicity profile of pembrolizumab in combination with the 3 prescribed chemotherapy regimens.

In part 2 of the study, 847 patients were randomized to either the experimental arm of pembrolizumab plus chemotherapy or the comparator arm of placebo in saline form on day 1 of each 21-day cycle plus chemotherapy. The primary end points of part 2 are PFS and overall survival (OS) in all patients, OS in patients with a combined positive score (CPS) ≥1, and PFS and OS in patients with PD-L1 CPS ≥10. Secondary end points included the objective response rate, duration of response, disease control rate, and safety.

Pembrolizumab has prior indications for several malignancies, some of which include melanoma, non—small cell lung cancer, small cell lung cancer, head and neck squamous cell cancer, classical Hodgkin lymphoma, urothelial carcinoma, gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, renal cell carcinoma, primary mediastinal large B-cell lymphoma, and microsatellite instability–high cancer.

Treatment with pembrolizumab alone can lead to immune-related reactions such as pneumonitis, colitis, immune-mediated endocrinopathies, nephritis/renal dysfunction, and immune-mediated skin reactions. The infusion reactions associated with pembrolizumab include complications of allogeneic hematopoietic stem cell transplantation.

Based on the positive data from the KEYNOTE-355 trial, Merck plans to have a discussion with the FDA and other regulatory authorities.

Reference:

Merck’s Keytruda (pembrolizumab) in combination with chemotherapy met primary endpoint of progression-free survival (PFS) as first-line treatment for metastatic triple-negative breast cancer (mTNBC) [news release]. Kenilworth, NJ: Merck; February 12, 2020.https://bit.ly/2HtT4rj. Accessed February 12, 2020.