First Phase 3 Study To Demonstrate Statistically Significant Improvement in DFS in the Adjuvant Setting for Patients With Stage IB-IIIA NSCLC Regardless of PD-L1 Expression
KENILWORTH, NJ, USA I March 17, 2022 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP) today announced results from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS. The study found that adjuvant treatment with KEYTRUDA significantly improved disease-free survival (DFS), one of the dual primary endpoints, reducing the risk of disease recurrence or death by 24% compared to placebo (hazard ratio [HR]=0.76 [95% CI, 0.63-0.91]; p=0.0014) in patients with stage IB (≥4 centimeters) to IIIA non-small cell lung cancer (NSCLC) following surgical resection regardless of PD-L1 expression. Median DFS was 53.6 months for KEYTRUDA versus 42.0 months for placebo, an improvement of nearly one year. These data are being presented today during a European Society for Medical Oncology (ESMO) Virtual Plenary and will be shared with regulatory authorities worldwide.
“These are the first positive results for KEYTRUDA in the adjuvant setting for non-small cell lung cancer, and represent the sixth positive pivotal study evaluating a KEYTRUDA-based regimen in earlier stages of cancer,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “KEYTRUDA has become foundational in the treatment of metastatic non-small cell lung cancer, and we are pleased to present these data showing the potential of KEYTRUDA to help more patients with lung cancer in earlier stages of disease. We thank the patients, their caregivers and investigators for participating in this study.”
As previously announced, there was also an improvement in DFS for patients whose tumors express PD-L1 (tumor proportion score [TPS] ≥50%) treated with KEYTRUDA compared to placebo, the other dual primary endpoint; these results did not reach statistical significance per the pre-specified statistical plan (HR=0.82 [95% CI, 0.57-1.18]; p=0.14). Among these patients, median DFS was not reached in either arm. Additionally, a favorable trend in overall survival (OS), a key secondary endpoint, was observed for KEYTRUDA versus placebo regardless of PD-L1 expression (HR=0.87 [95% CI, 0.67-1.15]; p=0.17); these OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial will continue to evaluate DFS in patients whose tumors express high levels of PD-L1 (TPS ≥50%) and OS. The safety profile of KEYTRUDA in this study was consistent with that observed in previously reported studies.
“Lung cancer is most treatable at earlier stages, and adding treatment after surgery may help reduce the risk of recurrence,” said Professor Mary O’Brien, consultant medical oncologist and head of the Lung Unit at The Royal Marsden NHS Foundation Trust and professor of practice (medical oncology) at Imperial College London, as well as co-principal investigator. “We are encouraged by these new Phase 3 data, as they represent the first time adjuvant immunotherapy has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with stage IB-IIIA non-small cell lung cancer.”
“While significant advancements have been made in the treatment of metastatic non-small cell lung cancer, there remains an unmet need for patients with earlier stages of this disease, as up to 43% of them will experience disease recurrence following surgery,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain and co-principal investigator. “The positive disease-free survival data observed in this study with the use of KEYTRUDA in the adjuvant setting has the potential to have important implications for how we treat patients with stage IB-IIIA non-small cell lung cancer.”
In addition to KEYNOTE-091, five other pivotal trials evaluating a KEYTRUDA-based regimen in patients with earlier stages of cancer met their primary endpoint(s). These trials included: KEYNOTE-716 in stage IIB and IIC melanoma; KEYNOTE-054 in stage III melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; and KEYNOTE-057 in Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer.
Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC include KEYNOTE-091, KEYNOTE-671, KEYNOTE-867 and KEYLYNK-012.
Study Design and Additional Data From KEYNOTE-091
KEYNOTE-091, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS, is a randomized, Phase 3 trial (ClinicalTrials.gov, NCT02504372) sponsored by Merck and conducted in collaboration with EORTC and ETOP evaluating KEYTRUDA compared to placebo for the adjuvant treatment of patients with stage IB (≥4 centimeters) to IIIA NSCLC following surgical resection (lobectomy or pneumonectomy) and with adjuvant chemotherapy when indicated. The dual primary endpoints are DFS in the overall population and in patients whose tumors express PD-L1 (TPS ≥50%). Disease-free survival is calculated as the time from randomization to the date of disease recurrence, occurrence of second primary lung cancer, occurrence of second malignancy, or death from any cause, whichever occurs first. The secondary endpoints include OS and lung cancer-specific survival (the time from randomization to date of death due to lung cancer specifically). The study randomized 1,177 patients (1:1) to receive either KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for one year or maximum 18 doses; n=590); or placebo (IV Q3W for one year or maximum 18 doses; n=587). The median number of doses was 17 for KEYTRUDA and 18 for placebo. As of data cut-off for this interim analysis (September 20, 2021), median time from randomization to data cut-off was 35.6 months (range, 16.5-68.0 months).
Grade ≥3 adverse events occurred in 34.1% of patients receiving KEYTRUDA and 25.8% of patients receiving placebo. Adverse events resulting in discontinuation of any treatment occurred in 19.8% of patients receiving KEYTRUDA and 5.9% of patients receiving placebo; there were four treatment-related deaths in the KEYTRUDA arm and no treatment-related deaths in the placebo arm.
About EORTC
The European Organisation for Research and Treatment of Cancer (EORTC) is a non-governmental, non-profit organisation, which unites clinical cancer research experts, throughout Europe, to define better treatments for cancer patients to prolong survival and improve quality of life. Spanning from translational to large, prospective, multi-centre, phase III clinical trials that evaluate new therapies and treatment strategies as well as patient quality of life, its activities are coordinated from EORTC Headquarters, a unique international clinical research infrastructure, based in Brussels, Belgium.
For further information, please visit the EORTC website: www.eortc.org.
About ETOP
The European Thoracic Oncology Platform (ETOP) is a foundation promoting exchange and research in the field of thoracic malignancies in Europe. It is a not-for-profit organization, domiciled in Bern, Switzerland. Since 2009 ETOP been able to bring together international leaders in field of thoracic malignancies from all disciplines and has continuously enlarged its clinical trial and translational research activity in collaboration with many groups and institutions from 20 countries from Europe and beyond.
For further information, please visit the ETOP website: www.etop-eu.org.
About Lung Cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 82% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 24%, a 14% improvement over the last five years. Improving survival rates are due in part to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures as well as the introduction of new therapies.
About Merck’s Research in Lung Cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In advanced NSCLC, KEYTRUDA has four approved U.S. indications (see indications below), and is approved in advanced NSCLC in more than 95 countries. Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.
About Merck’s Early-Stage Cancer Clinical Program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.
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 Indications for KEYTRUDA® (pembrolizumab) in the U.S.
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.
Additional Indications for KEYTRUDA 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.
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 (BCG)-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 (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.
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
For over 130 years, Merck, known as MSD outside 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.
SOURCE: Merck
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First Phase 3 Study To Demonstrate Statistically Significant Improvement in DFS in the Adjuvant Setting for Patients With Stage IB-IIIA NSCLC Regardless of PD-L1 Expression
KENILWORTH, NJ, USA I March 17, 2022 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, the European Organisation for Research and Treatment of Cancer (EORTC) and the European Thoracic Oncology Platform (ETOP) today announced results from the pivotal Phase 3 KEYNOTE-091 trial, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS. The study found that adjuvant treatment with KEYTRUDA significantly improved disease-free survival (DFS), one of the dual primary endpoints, reducing the risk of disease recurrence or death by 24% compared to placebo (hazard ratio [HR]=0.76 [95% CI, 0.63-0.91]; p=0.0014) in patients with stage IB (≥4 centimeters) to IIIA non-small cell lung cancer (NSCLC) following surgical resection regardless of PD-L1 expression. Median DFS was 53.6 months for KEYTRUDA versus 42.0 months for placebo, an improvement of nearly one year. These data are being presented today during a European Society for Medical Oncology (ESMO) Virtual Plenary and will be shared with regulatory authorities worldwide.
“These are the first positive results for KEYTRUDA in the adjuvant setting for non-small cell lung cancer, and represent the sixth positive pivotal study evaluating a KEYTRUDA-based regimen in earlier stages of cancer,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “KEYTRUDA has become foundational in the treatment of metastatic non-small cell lung cancer, and we are pleased to present these data showing the potential of KEYTRUDA to help more patients with lung cancer in earlier stages of disease. We thank the patients, their caregivers and investigators for participating in this study.”
As previously announced, there was also an improvement in DFS for patients whose tumors express PD-L1 (tumor proportion score [TPS] ≥50%) treated with KEYTRUDA compared to placebo, the other dual primary endpoint; these results did not reach statistical significance per the pre-specified statistical plan (HR=0.82 [95% CI, 0.57-1.18]; p=0.14). Among these patients, median DFS was not reached in either arm. Additionally, a favorable trend in overall survival (OS), a key secondary endpoint, was observed for KEYTRUDA versus placebo regardless of PD-L1 expression (HR=0.87 [95% CI, 0.67-1.15]; p=0.17); these OS data are not mature and did not reach statistical significance at the time of this interim analysis. The trial will continue to evaluate DFS in patients whose tumors express high levels of PD-L1 (TPS ≥50%) and OS. The safety profile of KEYTRUDA in this study was consistent with that observed in previously reported studies.
“Lung cancer is most treatable at earlier stages, and adding treatment after surgery may help reduce the risk of recurrence,” said Professor Mary O’Brien, consultant medical oncologist and head of the Lung Unit at The Royal Marsden NHS Foundation Trust and professor of practice (medical oncology) at Imperial College London, as well as co-principal investigator. “We are encouraged by these new Phase 3 data, as they represent the first time adjuvant immunotherapy has demonstrated a statistically significant and clinically meaningful improvement in disease-free survival for patients with stage IB-IIIA non-small cell lung cancer.”
“While significant advancements have been made in the treatment of metastatic non-small cell lung cancer, there remains an unmet need for patients with earlier stages of this disease, as up to 43% of them will experience disease recurrence following surgery,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario Doce de Octubre, Madrid, Spain and co-principal investigator. “The positive disease-free survival data observed in this study with the use of KEYTRUDA in the adjuvant setting has the potential to have important implications for how we treat patients with stage IB-IIIA non-small cell lung cancer.”
In addition to KEYNOTE-091, five other pivotal trials evaluating a KEYTRUDA-based regimen in patients with earlier stages of cancer met their primary endpoint(s). These trials included: KEYNOTE-716 in stage IIB and IIC melanoma; KEYNOTE-054 in stage III melanoma; KEYNOTE-564 in renal cell carcinoma; KEYNOTE-522 in triple-negative breast cancer; and KEYNOTE-057 in Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer.
Merck has an extensive clinical development program in lung cancer and is advancing multiple registration-enabling studies, with research directed at earlier stages of disease and novel combinations. Key studies in earlier stages of NSCLC include KEYNOTE-091, KEYNOTE-671, KEYNOTE-867 and KEYLYNK-012.
Study Design and Additional Data From KEYNOTE-091
KEYNOTE-091, also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS, is a randomized, Phase 3 trial (ClinicalTrials.gov, NCT02504372) sponsored by Merck and conducted in collaboration with EORTC and ETOP evaluating KEYTRUDA compared to placebo for the adjuvant treatment of patients with stage IB (≥4 centimeters) to IIIA NSCLC following surgical resection (lobectomy or pneumonectomy) and with adjuvant chemotherapy when indicated. The dual primary endpoints are DFS in the overall population and in patients whose tumors express PD-L1 (TPS ≥50%). Disease-free survival is calculated as the time from randomization to the date of disease recurrence, occurrence of second primary lung cancer, occurrence of second malignancy, or death from any cause, whichever occurs first. The secondary endpoints include OS and lung cancer-specific survival (the time from randomization to date of death due to lung cancer specifically). The study randomized 1,177 patients (1:1) to receive either KEYTRUDA (200 mg intravenously [IV] every three weeks [Q3W] for one year or maximum 18 doses; n=590); or placebo (IV Q3W for one year or maximum 18 doses; n=587). The median number of doses was 17 for KEYTRUDA and 18 for placebo. As of data cut-off for this interim analysis (September 20, 2021), median time from randomization to data cut-off was 35.6 months (range, 16.5-68.0 months).
Grade ≥3 adverse events occurred in 34.1% of patients receiving KEYTRUDA and 25.8% of patients receiving placebo. Adverse events resulting in discontinuation of any treatment occurred in 19.8% of patients receiving KEYTRUDA and 5.9% of patients receiving placebo; there were four treatment-related deaths in the KEYTRUDA arm and no treatment-related deaths in the placebo arm.
About EORTC
The European Organisation for Research and Treatment of Cancer (EORTC) is a non-governmental, non-profit organisation, which unites clinical cancer research experts, throughout Europe, to define better treatments for cancer patients to prolong survival and improve quality of life. Spanning from translational to large, prospective, multi-centre, phase III clinical trials that evaluate new therapies and treatment strategies as well as patient quality of life, its activities are coordinated from EORTC Headquarters, a unique international clinical research infrastructure, based in Brussels, Belgium.
For further information, please visit the EORTC website: www.eortc.org.
About ETOP
The European Thoracic Oncology Platform (ETOP) is a foundation promoting exchange and research in the field of thoracic malignancies in Europe. It is a not-for-profit organization, domiciled in Bern, Switzerland. Since 2009 ETOP been able to bring together international leaders in field of thoracic malignancies from all disciplines and has continuously enlarged its clinical trial and translational research activity in collaboration with many groups and institutions from 20 countries from Europe and beyond.
For further information, please visit the ETOP website: www.etop-eu.org.
About Lung Cancer
Lung cancer is the leading cause of cancer death worldwide. In 2020 alone, there were more than 2.2 million new cases and 1.8 million deaths from lung cancer globally. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 82% of all cases. In the U.S., the overall five-year survival rate for patients diagnosed with lung cancer is 24%, a 14% improvement over the last five years. Improving survival rates are due in part to earlier detection and screening, reduction in smoking, advances in diagnostic and surgical procedures as well as the introduction of new therapies.
About Merck’s Research in Lung Cancer
Merck is advancing research aimed at transforming the way lung cancer is treated, with a goal of improving outcomes for patients affected by this deadly disease. Through nearly 200 clinical trials evaluating more than 36,000 patients around the world, Merck is at the forefront of lung cancer research. In advanced NSCLC, KEYTRUDA has four approved U.S. indications (see indications below), and is approved in advanced NSCLC in more than 95 countries. Among Merck’s research efforts are trials focused on evaluating KEYTRUDA in earlier stages of lung cancer as well as identifying new combinations and coformulations with KEYTRUDA.
About Merck’s Early-Stage Cancer Clinical Program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is studying KEYTRUDA in earlier disease states, with approximately 20 ongoing registrational studies across multiple types of cancer.
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 Indications for KEYTRUDA® (pembrolizumab) in the U.S.
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.
Additional Indications for KEYTRUDA 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.
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 (BCG)-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 (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.
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
For over 130 years, Merck, known as MSD outside 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.
SOURCE: Merck
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