KENILWORTH, N.J.–(BUSINESS WIRE) November 13, 2020 — Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved Keytruda, Merck’s anti-PD-1 therapy, in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (Combined Positive Score [CPS] ≥10) as determined by an FDA-approved test. The approval is based on results from the Phase 3 KEYNOTE-355 trial, where Keytruda in combination with chemotherapy – paclitaxel (pac), paclitaxel protein-bound (commonly known as nab-paclitaxel) or gemcitabine (gem) and carboplatin (carbo) – significantly reduced the risk of disease progression or death by 35% for patients whose tumors express PD-L1 (CPS ≥10) versus the same chemotherapy regimens alone (HR=0.65 [95% CI, 0.49, 0.86]; p=0.0012). Events were observed in 62% (n=136/220) of these patients receiving Keytruda in combination with pac, nab-paclitaxel or gem/carbo versus 77% (n=79/103) with the same chemotherapy regimens alone. In the trial, 38% of patients had tumors expressing PD-L1 with CPS ≥10. This indication is approved under accelerated approval based on progression-free survival (PFS); continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
“Approximately 15-20% of patients with breast cancer are diagnosed with triple-negative breast cancer, which is a difficult-to-treat and aggressive cancer,” said Dr. Hope Rugo, director of Breast Oncology and Clinical Trials Education, University of California San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center. “Notably, in KEYNOTE-355, Keytruda was combined with three different chemotherapy regimens: paclitaxel, nab-paclitaxel or gemcitabine and carboplatin. The approval of Keytruda in combination with chemotherapy gives physicians an important new option for appropriate patients.”
Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman.
“Today’s approval is a significant milestone, as it represents the first approval for Keytruda in the breast cancer setting,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “In the study supporting this approval, Keytruda in combination with paclitaxel, nab-paclitaxel or gemcitabine and carboplatin significantly improved progression-free survival for patients with advanced triple-negative breast cancer whose tumors express PD-L1 with CPS greater than or equal to 10 compared with the same chemotherapy regimens alone.”
Data Supporting the Approval
The accelerated approval was based on data from KEYNOTE-355 (ClinicalTrials.gov, NCT02819518), a multicenter, double-blind, randomized, placebo-controlled trial conducted in 847 patients with locally recurrent unresectable or metastatic TNBC, regardless of tumor PD-L1 expression, who had not been previously treated with chemotherapy in the metastatic setting. Patients were randomized (2:1) to receive either Keytruda (200 mg on Day 1 every three weeks) or placebo (on Day 1 every three weeks) in combination with the following chemotherapy; all medications were administered via intravenous infusion:
- Pac (90 mg/m2 on Days 1, 8 and 15 every 28 days); or
- Nab-paclitaxel (100 mg/m2 on Days 1, 8 and 15 every 28 days); or
- Gem/carbo (1,000 mg/m2 and AUC 2 mg/mL/min, respectively, on Days 1 and 8 every 21 days).
Randomization was stratified by chemotherapy treatment (pac or nab-paclitaxel vs. gem and carbo), tumor PD-L1 expression (CPS ≥1 vs. CPS <1) according to the PD-L1 IHC 22C3 pharmDx kit and prior treatment with the same class of chemotherapy in the neoadjuvant setting (yes vs. no). Assessment of tumor status was performed at Weeks 8, 16 and 24, then every nine weeks for the first year and every 12 weeks thereafter. The main efficacy outcome measure was PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ tested in the subgroup of patients with CPS ≥10. Additional efficacy outcome measures were overall survival, as well as objective response rate (ORR) and duration of response (DOR) as assessed by BICR.
The study population characteristics were: median age of 53 years (range, 22 to 85), 21% age 65 or older; 100% female; 68% White, 21% Asian and 4% Black; 60% ECOG PS of 0 and 40% ECOG PS of 1; and 68% were post-menopausal. Seventy-five percent of patients had tumor PD-L1 expression CPS ≥1 and 38% had tumor PD‑L1 expression CPS ≥10.
In KEYNOTE-355, efficacy results were in patients who were PD‑L1 positive with a CPS ≥10 (n=323) and randomized to receive Keytruda in combination with pac, nab-paclitaxel or gem/carbo compared with the same chemotherapy regimens alone. Keytruda in combination with pac, nab-paclitaxel or gem/carbo (n=220) reduced the risk of disease progression or death by 35% (HR=0.65 [95% CI, 0.49, 0.86]; p=0.0012), with a median PFS of 9.7 months (95% CI, 7.6, 11.3) versus 5.6 months (95% CI, 5.3, 7.5) with the same chemotherapy regimens alone (n=103). For PFS, 62% (n=136) of patients experienced an event with Keytruda in combination with pac, nab-paclitaxel or gem/carbo versus 77% (n=79) with the same chemotherapy regimens alone. For patients who received Keytruda in combination with pac, nab-paclitaxel or gem/carbo, the ORR was 53% (95% CI, 46, 60), with a complete response rate of 17% and a partial response rate of 36%. For patients treated with the same chemotherapy regimens alone, the ORR was 40% (95% CI, 30, 50), with a complete response rate of 13% and a partial response rate of 27%. Median DOR was 19.3 months (95% CI, 9.9, 29.8) with KEYTRUDA in combination with pac, nab-paclitaxel or gem/carbo versus 7.3 months (95% CI, 5.3, 15.8) with the same chemotherapy regimens alone.
In the study, the median duration of exposure to Keytruda was 5.7 months (range, 1 day to 33.0 months). Fatal adverse reactions occurred in 2.5% of patients (n=596) receiving Keytruda in combination with chemotherapy, including cardio-respiratory arrest (0.7%) and septic shock (0.3%). Serious adverse reactions occurred in 30% of patients receiving Keytruda in combination with pac, nab-paclitaxel, or gem/carbo. Serious adverse reactions observed in ≥2% of patients were pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). Keytruda was discontinued for adverse reactions in 11% of patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda (≥1%) were increased alanine aminotransferase (ALT) (2.2%), increased aspartate aminotransferase (AST) (1.5%), and pneumonitis (1.2%). Adverse reactions leading to the interruption of Keytruda occurred in 50% of patients. The most common adverse reactions leading to interruption of Keytruda (≥2%) were neutropenia (22%), thrombocytopenia (14%), anemia (7%), increased ALT (6%), leukopenia (5%), decreased white blood cell count (3.9%), and diarrhea (2%). The most common adverse reactions (all grades ≥20%) for Keytruda in combination with pac, nab-paclitaxel or gem/carbo were: fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% each), vomiting and rash (26% each), cough (23%), decreased appetite (21%), and headache (20%).
About Triple-Negative Breast Cancer (TNBC)
Triple-negative breast cancer is an aggressive type of breast cancer that characteristically has a high recurrence rate within the first five years after diagnosis. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Approximately 15-20% of patients with breast cancer are diagnosed with TNBC.
About Keytruda (pembrolizumab) Injection, 100 mg
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. 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 1,300 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.
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 the Merck Access Program for Keytruda
At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help appropriate patients who are prescribed Keytruda have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving Keytruda, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. More information is available by calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com.
About Merck’s Patient Support Program for Keytruda
Merck is committed to helping provide patients and their caregivers support throughout their treatment with KEYTRUDA. The KEY+YOU Patient Support Program provides a range of resources and support. For further information and to sign up, eligible patients may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com.
For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases – as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
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The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2019 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Source: Merck & Co., Inc.
Posted: November 2020
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- FDA Approves Merck’s Keytruda (pembrolizumab) for the Treatment of Patients with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma (cSCC) that is Not Curable by Surgery or Radiation – June 24, 2020
- FDA Approves Second Biomarker-Based Indication for Merck’s Keytruda (pembrolizumab), Regardless of Tumor Type – June 17, 2020
- FDA Approves Merck’s Keytruda (pembrolizumab) for Use at an Additional Recommended Dose of 400 mg Every Six Weeks for All Approved Adult Indications – April 28, 2020
- FDA Approves Keytruda (pembrolizumab) for Patients With BCG-Unresponsive, High-Risk, Non-Muscle Invasive Bladder Cancer – January 8, 2020
- FDA Approves Keytruda (pembrolizumab) plus Lenvima (lenvatinib) Combination Treatment for Patients with Certain Types of Endometrial Carcinoma – September 17, 2019
- FDA Approves Keytruda (pembrolizumab) for Recurrent Locally Advanced or Metastatic Squamous Cell Carcinoma of the Esophagus – July 31, 2019
- FDA Approves Keytruda (pembrolizumab) for the Treatment of Metastatic Small Cell Lung Cancer (SCLC) – June 18, 2019
- FDA Approves Keytruda (pembrolizumab) for First-Line Treatment of Head and Neck Squamous Cell Carcinoma – June 11, 2019
- FDA Approves Keytruda (pembrolizumab) in Combination With Inlyta (axitinib) as First-Line Treatment for Patients With Advanced Renal Cell Carcinoma (RCC) – April 22, 2019
- FDA Approves Expanded Monotherapy Label for Merck’s Keytruda (pembrolizumab) for First-Line Treatment of NSCLC – April 11, 2019
- FDA Approves Keytruda (pembrolizumab) for the Adjuvant Treatment of Patients with Melanoma with Involvement of Lymph Node(s) Following Complete Resection – February 19, 2019
- FDA Approves Keytruda (pembrolizumab) for the Treatment of Patients with Recurrent Locally Advanced or Metastatic Merkel Cell Carcinoma – December 19, 2018
- FDA Approves Keytruda (pembrolizumab) for the Treatment of Patients with Hepatocellular Carcinoma (HCC) Who Have Been Previously Treated with Sorafenib – November 9, 2018
- FDA Approves Keytruda (pembrolizumab) in Combination with Carboplatin and Either Paclitaxel or Nab-Paclitaxel for the First-Line Treatment of Patients with Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC) – October 30, 2018
- FDA Approves Expanded Label for Merck’s Keytruda (pembrolizumab) in Patients with Metastatic Nonsquamous NSCLC with No EGFR or ALK Genomic Tumor Aberrations – August 21, 2018
- FDA Approves Keytruda (pembrolizumab) for Treatment of Refractory or Relapsed Primary Mediastinal Large B-Cell Lymphoma (PMBCL) – June 13, 2018
- FDA Approves Keytruda (pembrolizumab) for Previously Treated Patients with Recurrent or Metastatic Cervical Cancer Whose Tumors Express PD-L1 – June 12, 2018
- FDA Approves Merck’s Keytruda (pembrolizumab) for Previously Treated Patients with Recurrent Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Cancer Whose Tumors Express PD-L1 – September 22, 2017
- FDA Approves Keytruda (pembrolizumab) as First Cancer Treatment for any Solid Tumor with a Specific Genetic Feature – May 23, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for Certain Patients with Locally Advanced or Metastatic Urothelial Carcinoma – May 18, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) as First-Line Combination Therapy for Patients with Metastatic Nonsquamous Non-Small Cell Lung Cancer (NSCLC), Irrespective of PD-L1 Expression – May 10, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for Classical Hodgkin Lymphoma (cHL) – March 15, 2017
- FDA Approves Merck’s Keytruda (pembrolizumab) for First-Line Treatment of Certain Patients with Metastatic Non-Small Cell Lung Cancer – October 24, 2016
- FDA Approves Merck’s Keytruda (pembrolizumab) for Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma – August 5, 2016
- FDA Approves Expanded Indication for Keytruda (pembrolizumab) for the Treatment of Patients with Advanced Melanoma – December 18, 2015
- FDA Approves Keytruda (pembrolizumab) for Advanced Non-Small Cell Lung Cancer – October 2, 2015
- FDA Approves Keytruda (pembrolizumab) for Advanced Melanoma – September 4, 2014
- Merck to Present New Data in Five Tumor Types from Studies Evaluating Pembrolizumab – September 2, 2014
- Merck’s Investigational Anti-PD-1 Antibody, Pembrolizumab, Under Regulatory Review in Europe for Advanced Melanoma – June 30, 2014
Keytruda (pembrolizumab) FDA Approval History
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