Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) in Combination With Chemotherapy for First-Line Treatment of PD-L1-Positive Metastatic Triple-Negative Breast Cancer

Sep 21, 2021 02:32 CST Updated 02:32

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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

Sept. 20, 2021 /BioonBIOON/ -- Merck & Co. recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval ofThe anti-PD-1 therapy Keytruda (pembrolizumab), in combination with chemotherapy, for the treatment ofTumorPD-L1-expressing (Combined Positive Score [CPS] ≥10), locally recurrent unresectable or metastatic triple-negative breast cancer previously untreated with chemotherapy for metastatic diseaseBreast cancer(TNBC) adult patients.

The CHMP's opinion will now be submitted to the European Commission (EC) for review, which typically renders a final decision within two months. The CHMP's positive opinion is based on the progression-free survival (PFS) and overall survival (OS) results from the pivotal Phase 3 KEYNOTE-355 trial (NCT02819518). Data show that, compared withCompared with patients receiving chemotherapy alone, patients treated with Keytruda in combination with chemotherapy (one of three regimens: nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin) demonstrated significant improvements in PFS and OS.

Triple-negative breast cancer (TNBC) is a type of breast cancer that tests negative for the overexpression of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). It is an aggressive breast cancer characterized by a high recurrence rate within the first 5 years following diagnosis. Approximately 10-15% of breast cancer patients areDiagnosisfor TNBC.

In November 2020, based on the interim analysis results of the KEYNOTE-355 trial, the United StatesFDAAccelerated Approval of Keytruda in Combination with Chemotherapy for TreatmentTumorPatients with locally recurrent unresectable or metastatic TNBC expressing PD-L1 (CPS ≥ 10). This approval marks the first approval of Keytruda in breast cancer.

Dr. Vicki Goodman, Vice President of Clinical Research at MSD Research Laboratories, stated: “TNBC grows and spreads faster than other types of breast cancer, resulting in a poorer prognosis. This positive opinion from the CHMP is an important step toward making a new KEYTRUDA immunotherapy regimen available to patients with metastatic TNBC in Europe. Importantly, this treatment regimen can be used in combination with various chemotherapy agents. We look forward to the European Commission's decision in the coming months.”

KEYNOTE-355 (NCT02819518) is a randomized, two-part, placebo-controlled phase 3 trial conducted in patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) who had not previously received chemotherapy for advanced disease, evaluating the efficacy and safety of Keytruda plus chemotherapy (one of 3 regimens) versus placebo plus chemotherapy (one of 3 regimens) as first-line treatment. In this study, chemotherapy consisted of one of the following 3 regimens per investigator's choice: nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin. The study endpoints included:TumorProgression-free survival (PFS) and overall survival (OS) in PD-L1-expressing patients (CPS ≥ 1 and CPS ≥ 10) and in all patients (intention-to-treat [ITT] population). Other endpoints include: objective response rate (ORR), duration of response (DOR), disease control rate (DCR), patient-reported outcomes (PRO), and safety.

Part 2 of the study enrolled 847 patients, who were randomized in a 2:1 ratio to receive: (1) Keytruda (200 mg every 3 weeks) + chemotherapy; (2) placebo + chemotherapy. Among the enrolled patients in each treatment group, approximately 75% had tumors expressing PD-L1 with a CPS ≥ 1 (Keytruda + chemotherapy group n=425/566; chemotherapy group n=211/281), approximately 38% of patientsTumorPD-L1 expression and CPS ≥ 10 (Keytruda + chemotherapy group, n = 220/566; chemotherapy group, n = 103/281).

Previously announced interim analysis data show that,InTumorIn patients with PD-L1 expression and CPS ≥ 10 (representing 38% of the study population), the risk of disease progression or death was significantly reduced by 35% in the Keytruda + chemotherapy group compared with the placebo + chemotherapy group (HR=0.65; 95% CI: 0.49-0.86; p=0.0012), with progression-free survival (PFS) demonstrating a statistically and clinically significant prolongation (median PFS: 9.7 months vs 5.6 months). Additionally, the objective response rate (ORR) was 53% in the Keytruda + chemotherapy group (complete response [CR] rate: 17%; partial response [PR] rate: 36%), compared with 40% in the placebo + chemotherapy group (CR: 13%; PR: 27%). The median duration of response (DOR) was 19.3 months in the Keytruda + chemotherapy group versus 7.3 months in the placebo + chemotherapy group.

The OS results recently presented at the ESMO Congress were consistent with the aforementioned interim analysis, namely: atTumorIn patients with PD-L1-expressing (CPS ≥ 10) locally recurrent unresectable or metastatic TNBC,Compared with chemotherapy, the Keytruda plus chemotherapy regimen provides a significant survival benefit. Specifically: compared with chemotherapy, Keytruda plus chemotherapy reduced the risk of death by 27% (HR=0.73, p=0.0093) and significantly prolonged survival (median OS: 23.0 months vs. 16.1 months).

It is worth noting that, based on the OS results,Keytruda is the first anti-PD-1 therapy that significantly prolongs survival in the aforementioned patient population when combined with chemotherapy. (Bioon.com）

Original Source:Merck Receives Positive EU CHMP Opinion for KEYTRUDA® (pembrolizumab) in Combination With Chemotherapy for Certain Patients With Locally Recurrent Unresectable or Metastatic Triple-Negative Breast Cancer Whose Tumors Express PD-L1 (CPS ≥10)