European Commission Approves Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy, With or Without Bevacizumab, for Patients With Persistent, Recurrent or Metastatic Cervical Cancer Whose Tumors Express PD-L1 (CPS ≥1)

First Immunotherapy-Based Regimen Approved in Europe for These Patients With Persistent, Recurrent or Metastatic Cervical Cancer

Approval Based on Overall Survival Benefit Demonstrated in Phase 3 KEYNOTE-826 Trial

KENILWORTH, NJ, USA I April 29, 2022 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the European Commission has approved KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy, with or without bevacizumab, for the treatment of persistent, recurrent or metastatic cervical cancer in adults whose tumors express PD-L1 (Combined Positive Score [CPS] ≥1). This approval is based on results from the Phase 3 KEYNOTE-826 trial, in which KEYTRUDA plus chemotherapy with or without bevacizumab (the KEYTRUDA regimen) demonstrated a statistically significant improvement in overall survival (OS) (HR=0.64 [95% CI, 0.50-0.81]; p=0.0001) and progression-free survival (PFS) (HR=0.62 [95% CI, 0.50-0.77]; p<0.0001) compared to chemotherapy with or without bevacizumab in this patient population. Additionally, more patients responded to the KEYTRUDA regimen, with an objective response rate (ORR) of 68% (95% CI, 62-74) versus 50% (95% CI, 44-56), respectively.

“After many years of limited progress in developing new treatment options for persistent, recurrent or metastatic cervical cancer, we saw notable improvements in overall survival in KEYNOTE-826, with a 36% reduction in the risk of death,” said Dr. Nicoletta Colombo, associate professor, University of Milan-Bicocca, and director, Gynecologic Oncology Program at the European Institute of Oncology in Milan, Italy. “With today’s approval, healthcare providers in the EU will be able to offer certain patients with advanced cervical cancer a long-awaited immunotherapy option that has shown significant improvement in overall survival.”

“Women diagnosed with persistent, recurrent or metastatic cervical cancer often have a low survival rate,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “The EU approval of this KEYTRUDA regimen for women with persistent, recurrent or metastatic cervical cancer whose tumors express PD-L1 CPS ≥1 is the first of its kind for an immunotherapy regimen in Europe and is another example of our continued commitment to delivering new therapies for patients with breast and gynecologic cancers.”

This approval allows marketing of this KEYTRUDA regimen in all 27 European Union member states plus Iceland, Lichtenstein, Norway and Northern Ireland.

Merck is rapidly expanding its extensive clinical development program for KEYTRUDA and several other investigational and approved medicines across gynecologic cancers, including evaluating KEYTRUDA for the treatment of locally advanced cervical cancer.

Additional Data and Safety from KEYNOTE-826

  • Median OS in patients whose tumors express PD-L1 CPS ≥1 was not reached (95% CI, 19.8-not reached [NR])for the KEYTRUDA regimen versus 16.3 months (95% CI, 14.5-19.4) for the chemotherapy regimen (HR=0.64 [95% CI, 0.50-0.81]; p=0.0001).
  • Median PFS in patients whose tumors express PD-L1 CPS ≥1 was 10.4 months (95% CI, 9.7-12.3) for the KEYTRUDA regimen versus 8.2 months (95% CI, 6.3-8.5) for the chemotherapy regimen (HR=0.62 [95% CI, 0.50-0.77]; p<0.0001).
  • The ORR in patients whose tumors express PD-L1 CPS ≥1 was 68% (95% CI, 62-74), including a complete response (CR) rate of 23% and a partial response (PR) rate of 45% for patients receiving the KEYTRUDA regimen versus 50% (95% CI, 44-56), including a CR rate of 13% and a PR rate of 37% for patients receiving the chemotherapy regimen.

The safety of KEYTRUDA in combination with chemotherapy has been evaluated in 3,123 patients with non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), esophageal carcinoma, triple-negative breast cancer (TNBC) or cervical cancer receiving KEYTRUDA 200 mg, 2 mg/kg bodyweight (bw) or 10 mg/kg bw every three weeks (Q3W) in clinical studies. In this patient population, the most frequent adverse reactions were anemia (55%), nausea (54%), fatigue (38%), neutropenia (36%), constipation and alopecia (35% each), diarrhea (34%), vomiting (28%) and decreased appetite (27%). Incidences of Grades 3‑5 adverse reactions were 67% for KEYTRUDA plus chemotherapy and 66% for chemotherapy alone in patients with NSCLC; 85% for KEYTRUDA plus chemotherapy and 84% for chemotherapy plus cetuximab in patients with HNSCC; 86% for KEYTRUDA plus chemotherapy and 83% for chemotherapy alone in patients with esophageal carcinoma; 78% for KEYTRUDA plus chemotherapy and 74% for chemotherapy alone in patients with TNBC; and 82% for KEYTRUDA plus chemotherapy and 75% for chemotherapy alone in patients with cervical cancer.

About KEYNOTE-826
KEYNOTE-826 (NCT03635567), is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial that enrolled 617 patients with persistent, recurrent or metastatic cervical cancer who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent. Patients were enrolled regardless of tumor PD-L1 expression status. Patients with autoimmune disease that required systemic therapy within two years of treatment or a medical condition that required immunosuppression were ineligible. The primary efficacy outcome measures were OS and PFS as assessed by investigator review according to RECIST v1.1. The secondary efficacy outcome measures included ORR and DOR as assessed by investigator review according to RECIST v1.1. In the KEYTRUDA arm, patients received KEYTRUDA 200 mg intravenously Q3W plus investigator’s choice of paclitaxel plus cisplatin or paclitaxel plus carboplatin Q3W, with or without bevacizumab, Q3W. In the chemotherapy placebo arm, patients received placebo plus investigator’s choice of paclitaxel plus cisplatin or paclitaxel plus carboplatin Q3W, with or without bevacizumab, Q3W. Of the 617 enrolled patients, 548 patients (89%) had tumors expressing PD-L1 (CPS ≥1). Among these 548 enrolled patients with tumors expressing PD-L1, 273 patients were randomized to receive the KEYTRUDA regimen, and 275 patients were randomized to receive the chemotherapy regimen.

About Merck in Cervical Cancer
Cervical cancer forms in a lower part of the uterus, in cells lining the cervix. All women are at risk for cervical cancer. It is most frequently diagnosed between the ages of 35 to 44. Cervical cancer is the fourth most common cancer in women globally. More than nine out of 10 cervical cancers have been associated with the human papillomavirus (HPV), a common virus that most sexually active people get at some point in their lives. For most people, HPV clears on its own; but for the very few who don’t clear the virus, HPV can lead to cervical cancer later in life. There is no way to know which people who have HPV will develop cancer. A critically important step is having regular cervical cancer screenings and talking with an HCP about prevention. Merck is committed to research to develop treatments for cervical cancer through a broad clinical development program across investigational and approved medicines.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA 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. Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,700 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

Non-Small Cell Lung Cancer
KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations. KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC. KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is:

  • stage III where patients are not candidates for surgical resection or definitive chemoradiation, or
  • metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Head and Neck Squamous Cell Cancer
KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC). KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test. KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult patients with relapsed or refractory classical Hodgkin lymphoma (cHL). KEYTRUDA is indicated for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy.

Primary Mediastinal Large B-Cell Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC):

  • who are not eligible for any platinum-containing chemotherapy, or
  • who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

Non-muscle Invasive Bladder Cancer
KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High or Mismatch Repair Deficient Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC).

Gastric Cancer
KEYTRUDA, in combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) (tumors with epicenter 1 to 5 centimeters above the GEJ) carcinoma that is not amenable to surgical resection or definitive chemoradiation either:

  • in combination with platinum- and fluoropyrimidine-based chemotherapy, or
  • as a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Cervical Cancer
KEYTRUDA, in combination with chemotherapy, with or without bevacizumab, is indicated for the treatment of patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test.

Hepatocellular Carcinoma
KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC). KEYTRUDA is indicated for the adjuvant treatment of patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions.

Endometrial Carcinoma
KEYTRUDA, as a single agent, is indicated for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR, as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Tumor Mutational Burden-High Cancer
KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with TMB-H central nervous system cancers have not been established.

Cutaneous Squamous Cell Carcinoma
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or locally advanced cSCC that is not curable by surgery or radiation.

Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

Merck’s Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck
At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

SOURCE: Merck

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