Longest Follow-Up Data for KEYTRUDA in Lung Cancer to Date Showed Five-Year Overall Survival Rate of 23.2% with KEYTRUDA in Treatment-Naïve Patients and 15.5% in Previously Treated Patients with Advanced NSCLC in KEYNOTE-001 Trial
Updated Overall Survival Analysis and New Data for Disease Progression After Next-Line Treatment (Progression-Free Survival 2) from KEYNOTE-189 Trial in Metastatic Nonsquamous NSCLC Also to be Presented
KENILWORTH, NJ, USA I June 01, 2019 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the presentation of five-year efficacy and safety data for KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) from the first KEYNOTE trial (Phase 1b KEYNOTE-001). In this study, KEYTRUDA demonstrated a five-year overall survival (OS) rate of 23.2% in treatment-naïve patients (n=101) and 15.5% in previously treated patients (n=449). Of note, the five-year OS rate among patients whose tumors expressed PD-L1 (tumor proportion score [TPS] ≥50%) was 29.6% in treatment-naïve patients (n=27) and 25.0% in previously treated patients (n=138). These findings, which represent the longest follow-up for KEYTRUDA in lung cancer, will be highlighted at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA9015) during the official press program and presented during a poster discussion on Sunday, June 2.
“Lung cancer is the leading cause of cancer death, and historically, the five-year survival rate has been around 5% for patients in the U.S. with advanced non-small cell lung cancer,” said Edward B. Garon, MD, MS, associate professor of medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles. “As a treating physician, it is encouraging to see the results of KEYNOTE-001, in which pembrolizumab showed a five-year overall survival rate of 23.2% in treatment-naïve patients and 15.5% in previously treated patients.”
After 60.6 months (range, 51.8 to 77.9) of median follow-up, results from KEYNOTE-001 demonstrated the effect of KEYTRUDA monotherapy across primary and secondary endpoints, including OS, objective response rate (ORR) and duration of response (DOR).
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Events
(n/N) |
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Median OS, mo
(95%, CI) |
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|
60-mo OS
rate (%) |
| Treatment-naïve |
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75/101* |
|
|
22.3 (17.1-32.3) |
|
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23.2 |
| TPS ≥50% |
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17/27 |
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35.4 (20.3-63.5) |
|
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29.6 |
| TPS 1%-49% |
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43/52 |
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19.5 (10.7-26.3) |
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15.7 |
| Previously treated |
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375/449† |
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10.5 (8.6-13.2) |
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15.5 |
| TPS ≥50% |
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104/138 |
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15.4 (10.6-18.8) |
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25.0 |
| TPS 1%-49% |
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146/168 |
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8.5 (6.0-12.6) |
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12.6 |
| TPS <1% |
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83/90 |
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8.6 (5.5-10.6) |
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3.5 |
*PD-L1 TPS <1% group not presented because of small patient numbers (n=12).
†PD-L1 TPS was unknown in 53 patients.
The investigator-reported ORR was 41.6% (95% CI, 31.9-51.8) in treatment-naïve patients and 22.9% (95% CI, 19.1-27.1) in previously treated patients. Median DOR was 16.8 months (range, 2.1+ to 55.7+) and 38.9 months (range, 1.0+ to 71.8+), respectively.
Among the 60 patients who received two or more years of treatment with KEYTRUDA, the five-year OS rate was 78.6% in treatment-naïve patients and 75.8% in previously treated patients. The ORR in these patients was 86% and 91%, respectively. Median DOR was 52.0 months (range, 10.2 to 55.7+) in treatment-naïve patients and was not reached (range, 12.5 to 71.8+) in previously treated patients.
The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced NSCLC. Treatment-related adverse events (TRAEs) of any grade occurred in 71% (n=388) of patients receiving KEYTRUDA; grade 3-5 TRAEs occurred in 13% (n=69) of patients. Immune-mediated adverse events were reported in 17% (n=92) of patients. Hypothyroidism was the most commonly reported immune-mediated adverse event, followed by pneumonitis, hyperthyroidism and skin toxicities.
“Five-year survival is a significant milestone for patients with advanced non-small cell lung cancer, and it is encouraging to see the long-term overall survival rates from our first KEYNOTE study,” said Dr. Roy Baynes, senior vice president and chief medical officer, Merck Research Laboratories. “These five-year data provide important insights into the long-term safety and efficacy of KEYTRUDA in patients with advanced non-small cell lung cancer.”
Additional Lung Cancer Data from KEYNOTE-189 (Abstract #9013)
New and updated data from the Phase 3 KEYNOTE-189 trial evaluating KEYTRUDA in combination with ALIMTA® (pemetrexed) and platinum (cisplatin or carboplatin) for the first-line treatment of metastatic nonsquamous NSCLC compared with pemetrexed plus platinum alone, will also be presented on Sunday, June 2 at ASCO (Abstract #9013). An updated analysis of the OS endpoint showed that after a median follow-up of 18.7 months (range, 0.2 to 30.9), KEYTRUDA in combination with pemetrexed-platinum chemotherapy reduced the risk of death by 44% compared with chemotherapy alone (HR=0.56 [95% CI, 0.45-0.70]; median OS 22.0 months vs. 10.7 months). An improvement in progression-free survival (PFS) was also observed, with a 52% reduction in the risk of progression or death compared with chemotherapy alone (HR=0.48 [95% CI, 0.40-0.58]; median PFS 9.0 months vs. 4.9 months). Fifty four percent of patients in the chemotherapy alone arm received subsequent immunotherapy, including 41% who received in-study crossover.
New findings at ASCO from KEYNOTE-189 also include the first-time presentation of the progression-free survival 2 (PFS2) study endpoint, a clinical endpoint used to assess the impact of next-line treatment on disease control, in the entire study population and different PD-L1 subgroups. Among patients who received KEYTRUDA in combination with chemotherapy, findings showed a 51% reduction in risk from time of randomization to objective tumor progression on next-line treatment or death from any cause, whichever comes first, compared with patients who received chemotherapy alone (HR=0.49 [95% CI, 0.40-0.59]; median PFS2 17.0 months vs. 9.0 months). Results were consistent across all three PD-L1 categories evaluated – with a 54% reduction in patients with a TPS <1% (HR=0.46 [95% CI, 0.33-0.66]), a 41% reduction in patients with a TPS of 1-49% (HR=0.59 [95% CI, 0.41-0.86]), and a 53% reduction in patients with a TPS ≥50% (HR=0.47 [95% CI, 0.33-0.69]).
Grade 3-5 adverse events from any cause occurred in 71.9% (n=291) of patients who received KEYTRUDA in combination with chemotherapy and 66.8% (n=135) in the chemotherapy alone arm. Adverse events leading to discontinuation of any treatment component occurred in 33.6% (n=136) of patients who received KEYTRUDA in combination with chemotherapy and 16.3% (n=33) in the chemotherapy alone arm. There were two deaths in the KEYTRUDA combination arm from immune-mediated adverse events and infusion reactions. KEYNOTE-189 was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA®).
Study Design of KEYNOTE-001 (Abstract #LBA9015)
KEYNOTE-001 (ClinicalTrials.gov, NCT01295827) is a Phase 1b multicenter, open-label, multi-cohort trial evaluating KEYTRUDA in various advanced cancers, including 550 patients with either treatment-naïve or previously treated advanced NSCLC. Patients received 2 mg/kg or 10 mg/kg of KEYTRUDA every three weeks (Q3W) or 10 mg/kg of KEYTRUDA every two weeks until unacceptable toxicity or disease progression. The primary endpoint was ORR; secondary endpoints included PFS, OS and DOR.
Study Design of KEYNOTE-189 (Abstract #9013)
KEYNOTE-189 (ClinicalTrials.gov, NCT02578680) is a pivotal Phase 3, randomized, double-blind, placebo-controlled trial of 616 untreated patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor aberrations designed to evaluate the efficacy of KEYTRUDA in combination with pemetrexed and cisplatin or carboplatin (n=410), compared with pemetrexed and cisplatin or carboplatin alone (n=206). Patients were randomized 2:1 to receive KEYTRUDA 200 mg, cisplatin or carboplatin, and pemetrexed intravenously Q3W for four cycles followed by KEYTRUDA 200 mg for up to 24 months and pemetrexed Q3W (n=410); or cisplatin or carboplatin and pemetrexed intravenously Q3W for four cycles followed by pemetrexed Q3W (n=206). Treatment continued until progression of disease or unacceptable toxicity. The dual primary endpoints were OS and PFS; secondary endpoints included ORR and DOR.
About Lung Cancer
Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10 to 15% of all lung cancers. Between 2008 and 2014, the five-year survival rate for patients diagnosed in the U.S. with advanced NSCLC was only 5%. Moreover, approximately 50% of metastatic NSCLC patients in the U.S. will not receive second-line therapy.
About KEYTRUDA® (pembrolizumab) Injection, 100mg
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 1,000 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.
KEYTRUDA® (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. The recommended dose of KEYTRUDA in patients with unresectable or metastatic melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence.
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 stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
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.
In NSCLC, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, as appropriate.
Head and Neck Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. 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. In HNSCC, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. 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. In adults with cHL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
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. 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 confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy.
In adults with PMBCL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with PMBCL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Microsatellite Instability-High (MSI-H) 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, or
- colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
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.
In adult patients with MSI-H cancer, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with MSI-H cancer, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. 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 recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Cervical Cancer
KEYTRUDA 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. 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 recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity or up to 24 months in patients without disease progression.
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. The recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. 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 recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma. In renal cell carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg axitinib orally twice daily until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months in patients without disease progression. When axitinib is used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. See also the Prescribing Information for recommended axitinib dosing information.
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 more than a century, Merck, a leading global biopharmaceutical company 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. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
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Longest Follow-Up Data for KEYTRUDA in Lung Cancer to Date Showed Five-Year Overall Survival Rate of 23.2% with KEYTRUDA in Treatment-Naïve Patients and 15.5% in Previously Treated Patients with Advanced NSCLC in KEYNOTE-001 Trial
Updated Overall Survival Analysis and New Data for Disease Progression After Next-Line Treatment (Progression-Free Survival 2) from KEYNOTE-189 Trial in Metastatic Nonsquamous NSCLC Also to be Presented
KENILWORTH, NJ, USA I June 01, 2019 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the presentation of five-year efficacy and safety data for KEYTRUDA, Merck’s anti-PD-1 therapy, as monotherapy in patients with advanced non-small cell lung cancer (NSCLC) from the first KEYNOTE trial (Phase 1b KEYNOTE-001). In this study, KEYTRUDA demonstrated a five-year overall survival (OS) rate of 23.2% in treatment-naïve patients (n=101) and 15.5% in previously treated patients (n=449). Of note, the five-year OS rate among patients whose tumors expressed PD-L1 (tumor proportion score [TPS] ≥50%) was 29.6% in treatment-naïve patients (n=27) and 25.0% in previously treated patients (n=138). These findings, which represent the longest follow-up for KEYTRUDA in lung cancer, will be highlighted at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA9015) during the official press program and presented during a poster discussion on Sunday, June 2.
“Lung cancer is the leading cause of cancer death, and historically, the five-year survival rate has been around 5% for patients in the U.S. with advanced non-small cell lung cancer,” said Edward B. Garon, MD, MS, associate professor of medicine, Jonsson Comprehensive Cancer Center, University of California, Los Angeles. “As a treating physician, it is encouraging to see the results of KEYNOTE-001, in which pembrolizumab showed a five-year overall survival rate of 23.2% in treatment-naïve patients and 15.5% in previously treated patients.”
After 60.6 months (range, 51.8 to 77.9) of median follow-up, results from KEYNOTE-001 demonstrated the effect of KEYTRUDA monotherapy across primary and secondary endpoints, including OS, objective response rate (ORR) and duration of response (DOR).
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Events
(n/N) |
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Median OS, mo
(95%, CI) |
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60-mo OS
rate (%) |
| Treatment-naïve |
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75/101* |
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22.3 (17.1-32.3) |
|
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23.2 |
| TPS ≥50% |
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17/27 |
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35.4 (20.3-63.5) |
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29.6 |
| TPS 1%-49% |
|
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43/52 |
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19.5 (10.7-26.3) |
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|
15.7 |
| Previously treated |
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375/449† |
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10.5 (8.6-13.2) |
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15.5 |
| TPS ≥50% |
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104/138 |
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15.4 (10.6-18.8) |
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25.0 |
| TPS 1%-49% |
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146/168 |
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8.5 (6.0-12.6) |
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12.6 |
| TPS <1% |
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83/90 |
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8.6 (5.5-10.6) |
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3.5 |
*PD-L1 TPS <1% group not presented because of small patient numbers (n=12).
†PD-L1 TPS was unknown in 53 patients.
The investigator-reported ORR was 41.6% (95% CI, 31.9-51.8) in treatment-naïve patients and 22.9% (95% CI, 19.1-27.1) in previously treated patients. Median DOR was 16.8 months (range, 2.1+ to 55.7+) and 38.9 months (range, 1.0+ to 71.8+), respectively.
Among the 60 patients who received two or more years of treatment with KEYTRUDA, the five-year OS rate was 78.6% in treatment-naïve patients and 75.8% in previously treated patients. The ORR in these patients was 86% and 91%, respectively. Median DOR was 52.0 months (range, 10.2 to 55.7+) in treatment-naïve patients and was not reached (range, 12.5 to 71.8+) in previously treated patients.
The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced NSCLC. Treatment-related adverse events (TRAEs) of any grade occurred in 71% (n=388) of patients receiving KEYTRUDA; grade 3-5 TRAEs occurred in 13% (n=69) of patients. Immune-mediated adverse events were reported in 17% (n=92) of patients. Hypothyroidism was the most commonly reported immune-mediated adverse event, followed by pneumonitis, hyperthyroidism and skin toxicities.
“Five-year survival is a significant milestone for patients with advanced non-small cell lung cancer, and it is encouraging to see the long-term overall survival rates from our first KEYNOTE study,” said Dr. Roy Baynes, senior vice president and chief medical officer, Merck Research Laboratories. “These five-year data provide important insights into the long-term safety and efficacy of KEYTRUDA in patients with advanced non-small cell lung cancer.”
Additional Lung Cancer Data from KEYNOTE-189 (Abstract #9013)
New and updated data from the Phase 3 KEYNOTE-189 trial evaluating KEYTRUDA in combination with ALIMTA® (pemetrexed) and platinum (cisplatin or carboplatin) for the first-line treatment of metastatic nonsquamous NSCLC compared with pemetrexed plus platinum alone, will also be presented on Sunday, June 2 at ASCO (Abstract #9013). An updated analysis of the OS endpoint showed that after a median follow-up of 18.7 months (range, 0.2 to 30.9), KEYTRUDA in combination with pemetrexed-platinum chemotherapy reduced the risk of death by 44% compared with chemotherapy alone (HR=0.56 [95% CI, 0.45-0.70]; median OS 22.0 months vs. 10.7 months). An improvement in progression-free survival (PFS) was also observed, with a 52% reduction in the risk of progression or death compared with chemotherapy alone (HR=0.48 [95% CI, 0.40-0.58]; median PFS 9.0 months vs. 4.9 months). Fifty four percent of patients in the chemotherapy alone arm received subsequent immunotherapy, including 41% who received in-study crossover.
New findings at ASCO from KEYNOTE-189 also include the first-time presentation of the progression-free survival 2 (PFS2) study endpoint, a clinical endpoint used to assess the impact of next-line treatment on disease control, in the entire study population and different PD-L1 subgroups. Among patients who received KEYTRUDA in combination with chemotherapy, findings showed a 51% reduction in risk from time of randomization to objective tumor progression on next-line treatment or death from any cause, whichever comes first, compared with patients who received chemotherapy alone (HR=0.49 [95% CI, 0.40-0.59]; median PFS2 17.0 months vs. 9.0 months). Results were consistent across all three PD-L1 categories evaluated – with a 54% reduction in patients with a TPS <1% (HR=0.46 [95% CI, 0.33-0.66]), a 41% reduction in patients with a TPS of 1-49% (HR=0.59 [95% CI, 0.41-0.86]), and a 53% reduction in patients with a TPS ≥50% (HR=0.47 [95% CI, 0.33-0.69]).
Grade 3-5 adverse events from any cause occurred in 71.9% (n=291) of patients who received KEYTRUDA in combination with chemotherapy and 66.8% (n=135) in the chemotherapy alone arm. Adverse events leading to discontinuation of any treatment component occurred in 33.6% (n=136) of patients who received KEYTRUDA in combination with chemotherapy and 16.3% (n=33) in the chemotherapy alone arm. There were two deaths in the KEYTRUDA combination arm from immune-mediated adverse events and infusion reactions. KEYNOTE-189 was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA®).
Study Design of KEYNOTE-001 (Abstract #LBA9015)
KEYNOTE-001 (ClinicalTrials.gov, NCT01295827) is a Phase 1b multicenter, open-label, multi-cohort trial evaluating KEYTRUDA in various advanced cancers, including 550 patients with either treatment-naïve or previously treated advanced NSCLC. Patients received 2 mg/kg or 10 mg/kg of KEYTRUDA every three weeks (Q3W) or 10 mg/kg of KEYTRUDA every two weeks until unacceptable toxicity or disease progression. The primary endpoint was ORR; secondary endpoints included PFS, OS and DOR.
Study Design of KEYNOTE-189 (Abstract #9013)
KEYNOTE-189 (ClinicalTrials.gov, NCT02578680) is a pivotal Phase 3, randomized, double-blind, placebo-controlled trial of 616 untreated patients with metastatic nonsquamous NSCLC and no EGFR or ALK genomic tumor aberrations designed to evaluate the efficacy of KEYTRUDA in combination with pemetrexed and cisplatin or carboplatin (n=410), compared with pemetrexed and cisplatin or carboplatin alone (n=206). Patients were randomized 2:1 to receive KEYTRUDA 200 mg, cisplatin or carboplatin, and pemetrexed intravenously Q3W for four cycles followed by KEYTRUDA 200 mg for up to 24 months and pemetrexed Q3W (n=410); or cisplatin or carboplatin and pemetrexed intravenously Q3W for four cycles followed by pemetrexed Q3W (n=206). Treatment continued until progression of disease or unacceptable toxicity. The dual primary endpoints were OS and PFS; secondary endpoints included ORR and DOR.
About Lung Cancer
Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10 to 15% of all lung cancers. Between 2008 and 2014, the five-year survival rate for patients diagnosed in the U.S. with advanced NSCLC was only 5%. Moreover, approximately 50% of metastatic NSCLC patients in the U.S. will not receive second-line therapy.
About KEYTRUDA® (pembrolizumab) Injection, 100mg
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 1,000 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.
KEYTRUDA® (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma. The recommended dose of KEYTRUDA in patients with unresectable or metastatic melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity.
KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection. The recommended dose of KEYTRUDA for the adjuvant treatment of adult patients with melanoma is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease recurrence, unacceptable toxicity, or for up to 12 months in patients without disease recurrence.
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 stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation, or metastatic NSCLC, and whose tumors express PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
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.
In NSCLC, the recommended dose of KEYTRUDA is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for the chemotherapy agents administered in combination with KEYTRUDA, as appropriate.
Head and Neck Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. 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. In HNSCC, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Classical Hodgkin Lymphoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. 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. In adults with cHL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
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. 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 confirmatory trials. KEYTRUDA is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy.
In adults with PMBCL, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with PMBCL, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Urothelial Carcinoma
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.
In locally advanced or metastatic urothelial carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Microsatellite Instability-High (MSI-H) 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, or
- colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.
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.
In adult patients with MSI-H cancer, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with MSI-H cancer, KEYTRUDA is administered as an intravenous infusion over 30 minutes at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Gastric Cancer
KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. 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 recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Cervical Cancer
KEYTRUDA 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. 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 recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity or up to 24 months in patients without disease progression.
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. The recommended dose of KEYTRUDA is 200 mg as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Merkel Cell Carcinoma
KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma. 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 recommended dose of KEYTRUDA in adults is 200 mg administered as an intravenous infusion over 30 minutes every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The recommended dose of KEYTRUDA in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
Renal Cell Carcinoma
KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma. In renal cell carcinoma, KEYTRUDA 200 mg is administered as an intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg axitinib orally twice daily until disease progression, unacceptable toxicity, or for KEYTRUDA, up to 24 months in patients without disease progression. When axitinib is used in combination with KEYTRUDA, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer. See also the Prescribing Information for recommended axitinib dosing information.
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 more than a century, Merck, a leading global biopharmaceutical company 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. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world – including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
SOURCE: Merck
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