Findings to Be Presented at 2017 ASCO Annual Meeting Also Include Updated Data Evaluating Duration of Response in Previously Untreated (First-Line) Urothelial Carcinoma Patients Ineligible for Cisplatin-Based Therapy
KENILWORTH, NJ, USA I June 4, 2017 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced updated results from KEYNOTE-045 and KEYNOTE-052, two studies investigating KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. These data – which include updated survival and biomarker analyses – demonstrate the clinical benefit of KEYTRUDA as a second-line therapy for patients post-platinum failure and as a first-line treatment for patients ineligible for cisplatin-based therapy. Specifically, in the second-line setting, KEYTRUDA improved overall survival (OS) compared to chemotherapy – reducing the risk of death by 30 percent (HR, 0.70 [95% CI, 0.57-0.86], p = 0.0004) – and, in the first-line setting, KEYTRUDA demonstrated an overall response rate (ORR) of 29 percent (95% CI, 25-34). Findings will be presented in two oral sessions at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on Monday, June 5, from 8:12 to 8:36 a.m. CDT (Location: Arie Crown Theater) (Abstracts #4501 and #4502).
“Historically, there have been limited treatment options for patients with advanced urothelial bladder cancer,” said Dean F. Bajorin, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center. “For patients with this devastating disease, the efficacy and safety profile we have observed with KEYTRUDA in these treatment settings represent an important new option.”
“The updated data at ASCO in previously treated urothelial cancer patients continue to support the overall survival benefit we have observed in the second-line treatment setting and the response rates demonstrated in cisplatin-ineligible patients,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “Beyond these two studies, we are studying KEYTRUDA in other treatment settings and look forward to executing on our robust clinical development program in bladder cancer.”
The KEYTRUDA (pembrolizumab) clinical development program includes more than 30 tumor types in more than 500 clinical trials, including more than 300 trials that combine KEYTRUDA with other cancer treatments. Currently, Merck has the largest immuno-oncology clinical development program in bladder cancer, with 29 trials underway involving KEYTRUDA as monotherapy and in combination, including four registration-enabling studies.
Data in Second-Line Post-Platinum Failure Patients, KEYNOTE-045 (Abstract #4501)
KEYNOTE-045 is a multicenter, randomized, active-controlled, phase 3 trial, investigating KEYTRUDA in 542 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy (additional details on the trial design are provided below). Data to be presented at ASCO are based on longer follow-up (median follow-up of 18.5 months as of Jan. 18, 2017; range: 14.2-26.5), which continues to show a superior OS advantage with KEYTRUDA compared to chemotherapy in the second-line treatment of patients with advanced urothelial carcinoma who have progressed during or following platinum-containing chemotherapy, regardless of PD-L1 expression.
Analyses of the primary endpoints showed a 30 percent reduction in the risk of death with KEYTRUDA (n=270) compared to chemotherapy (n=272) (HR, 0.70 [95% CI, 0.57-0.86], p = 0.0004). The median OS with KEYTRUDA was 10.3 months (95% CI, 8.0-12.3) versus 7.4 months with chemotherapy (95% CI, 6.1-8.1). As previously reported, there was no significant improvement in progression-free survival (PFS) between arms (HR, 0.96 [95% CI, 0.79-1.16], p= 0.32). The median PFS was 2.1 months (95% CI, 2.0-2.2) in the KEYTRUDA arm and 3.3 months (95% CI, 2.4-3.5) in the chemotherapy arm. The six-month, 12-month and 18-month PFS rates in the KEYTRUDA arm were 28.8 percent, 17.6 percent and 16.8 percent, respectively; the six-month, 12-month and 18-month PFS rates in the chemotherapy arm were 28.4 percent, 7.9 percent and 3.5 percent, respectively.
Analyses of the secondary endpoints showed a higher ORR with KEYTRUDA compared to chemotherapy. In patients treated with KEYTRUDA, the ORR was 21.1 percent – with a complete response rate of 7.8 percent and a partial response rate of 13.3 percent. In patients treated with chemotherapy, the ORR was 11.0 percent – with a complete response rate of 2.9 percent and a partial response rate of 8.1 percent. The median duration of response had not been reached in the KEYTRUDA (pembrolizumab) arm (range: 1.6+-20.7+) and was 4.4 months in the chemotherapy arm (range: 1.4+-20.3+).
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade 1-2 treatment-related adverse events in the KEYTRUDA arm included anemia, asthenia, constipation, decreased appetite, diarrhea, fatigue, nausea, peripheral neuropathy, peripheral sensory neuropathy and pruritus. Grade 3-5 treatment-related adverse events in the KEYTRUDA arm included anemia, asthenia, decreased neutrophils, diarrhea, fatigue, nausea and pruritus. Grade 3-5 immune-mediated adverse events included adrenal insufficiency, colitis, nephritis, pneumonitis and severe skin reaction.
Data in First-Line Cisplatin-Ineligible Patients, KEYNOTE-052 (Abstract #4502)
KEYNOTE-052 is a multicenter, open-label, single-arm phase 2 trial, investigating KEYTRUDA in 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy (additional details on the trial design are provided below). Findings to be presented at ASCO, which include the full study population and longer follow-up, show that in the first-line treatment setting many patients with cisplatin-ineligible advanced urothelial carcinoma treated with KEYTRUDA continue to experience complete or partial responses.
In the full study population (n=370), the efficacy analysis showed an ORR of 29 percent (95% CI, 25-34) – with a complete response rate of seven percent (95% CI, 5-10) and a partial response rate of 22 percent (95% CI, 18-27). At the time of analysis, 67 percent of responses were ongoing – of which 82 percent had lasted six months or longer. The median duration of response had not been reached at the time of analysis (95% CI, 12 months-not reached).
The study included a training set (the first 100 patients enrolled), which was used to identify the CPS cut-point for PD-L1 expression, and a validation set (which includes all subsequent 270 evaluable patients) intended to validate the combined positive score (CPS) cut-point. Of the 270 patients in the validation set, in patients with PD-L1 expression of less than 10 percent (CPS <10%), the ORR was 23 percent (95% CI, 17-29), with a complete response rate of three percent (95% CI, 1-6) and a partial response rate of 20 percent (95% CI, 15-27); in patients expressing PD-L1 equal to or greater than 10 percent (CPS ≥10%), the ORR was 51 percent (95% CI, 40-63), with a complete response rate of 18 percent (95% CI, 10-28) and a partial response rate of 34 percent (95% CI, 24-45).
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. The treatment-related adverse events (any grade occurring in 5% or more of patients [n=370] in descending order) were fatigue (18%), pruritus (17%), rash (12%), decreased appetite (10%), hypothyroidism (10%), diarrhea (9%), and nausea (8%). Grade 3-5 treatment-related adverse events observed (occurring in 3 or more of patients) were fatigue (2%), colitis (2%), muscle weakness (1%), alkaline phosphatase increase (1%), diarrhea (1%), pneumonitis (1%), AST increase (1%), asthenia (1%), hepatitis (1%), and ALT increase (1%). Grade 3-5 immune-mediated adverse events included: adrenal insufficiency, colitis, dermatitis bullous, diabetic ketoacidosis, hepatitis, myocarditis, pneumonitis, thyroiditis, type 1 diabetes mellitus, tubulointerstitial nephritis and rash.
About the KEYNOTE-045 and KEYNOTE-052 Studies
KEYNOTE-045 is a multicenter, randomized, active-controlled, phase 3 trial, investigating KEYTRUDA (pembrolizumab) in 542 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy. Patients were randomized to receive either KEYTRUDA 200 mg every three weeks (n=270) or investigator’s choice of any of the following chemotherapy regimens, all given intravenously, every three weeks (n=272): paclitaxel 175 mg/m2 (n=84), docetaxel 75 mg/m2 (n=84), or vinflunine 320 mg/m2 (n=87). Treatment continued until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months. The primary endpoints were OS and PFS, as assessed by blinded independent central review (BICR) per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1; additional efficacy outcome measures included ORR, as assessed by BICR per RECIST 1.1, and duration of response. Efficacy was assessed in all patients, as well as in patients with PD-L1 expression – as determined by a CPS of equal to or greater than 10 percent (CPS ≥10%) (KEYTRUDA arm: n=74/270; chemotherapy arm; n=90/272).
KEYNOTE-052 is a multicenter, open-label, single-arm phase 2 trial, investigating KEYTRUDA in 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy. Patients received KEYTRUDA at a dose of 200 mg every three weeks until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months. The study included a training set (the first 100 patients enrolled), which was used to identify the CPS cut-point for PD-L1 expression, and a validation set, which includes all subsequent 270 evaluable patients and will be used to validate the CPS cut-point. The primary endpoints include ORR in all patients enrolled in the study (total study population) and in patients with PD-L1 positive tumors (expression of one percent or more); secondary endpoints include duration of response, PFS and OS. Tumor response was measured according to RECIST v1.1 by central imaging vendor review.
About KEYTRUDA ® (pembrolizumab) Injection
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.
Studies of KEYTRUDA – from the largest immuno-oncology program in the industry with more than 500 trials – include a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand factors that predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including the exploration of several different biomarkers across a broad range of tumors.
KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single-dose vial.
KEYTRUDA (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, as a single agent, is also 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.
KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In metastatic NSCLC, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg 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 pemetrexed and carboplatin.
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 is administered at a fixed dose of 200 mg 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 three 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 is administered at a fixed dose of 200 mg 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 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 who are not eligible for cisplatin-containing chemotherapy. 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 also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma 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 (pembrolizumab) is administered at a fixed dose of 200 mg 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 is administered at a fixed dose of 200 mg 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 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
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.
As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 500 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic 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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Findings to Be Presented at 2017 ASCO Annual Meeting Also Include Updated Data Evaluating Duration of Response in Previously Untreated (First-Line) Urothelial Carcinoma Patients Ineligible for Cisplatin-Based Therapy
KENILWORTH, NJ, USA I June 4, 2017 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced updated results from KEYNOTE-045 and KEYNOTE-052, two studies investigating KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in certain patients with locally advanced or metastatic urothelial carcinoma, a type of bladder cancer. These data – which include updated survival and biomarker analyses – demonstrate the clinical benefit of KEYTRUDA as a second-line therapy for patients post-platinum failure and as a first-line treatment for patients ineligible for cisplatin-based therapy. Specifically, in the second-line setting, KEYTRUDA improved overall survival (OS) compared to chemotherapy – reducing the risk of death by 30 percent (HR, 0.70 [95% CI, 0.57-0.86], p = 0.0004) – and, in the first-line setting, KEYTRUDA demonstrated an overall response rate (ORR) of 29 percent (95% CI, 25-34). Findings will be presented in two oral sessions at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago on Monday, June 5, from 8:12 to 8:36 a.m. CDT (Location: Arie Crown Theater) (Abstracts #4501 and #4502).
“Historically, there have been limited treatment options for patients with advanced urothelial bladder cancer,” said Dean F. Bajorin, M.D., medical oncologist at Memorial Sloan Kettering Cancer Center. “For patients with this devastating disease, the efficacy and safety profile we have observed with KEYTRUDA in these treatment settings represent an important new option.”
“The updated data at ASCO in previously treated urothelial cancer patients continue to support the overall survival benefit we have observed in the second-line treatment setting and the response rates demonstrated in cisplatin-ineligible patients,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “Beyond these two studies, we are studying KEYTRUDA in other treatment settings and look forward to executing on our robust clinical development program in bladder cancer.”
The KEYTRUDA (pembrolizumab) clinical development program includes more than 30 tumor types in more than 500 clinical trials, including more than 300 trials that combine KEYTRUDA with other cancer treatments. Currently, Merck has the largest immuno-oncology clinical development program in bladder cancer, with 29 trials underway involving KEYTRUDA as monotherapy and in combination, including four registration-enabling studies.
Data in Second-Line Post-Platinum Failure Patients, KEYNOTE-045 (Abstract #4501)
KEYNOTE-045 is a multicenter, randomized, active-controlled, phase 3 trial, investigating KEYTRUDA in 542 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy (additional details on the trial design are provided below). Data to be presented at ASCO are based on longer follow-up (median follow-up of 18.5 months as of Jan. 18, 2017; range: 14.2-26.5), which continues to show a superior OS advantage with KEYTRUDA compared to chemotherapy in the second-line treatment of patients with advanced urothelial carcinoma who have progressed during or following platinum-containing chemotherapy, regardless of PD-L1 expression.
Analyses of the primary endpoints showed a 30 percent reduction in the risk of death with KEYTRUDA (n=270) compared to chemotherapy (n=272) (HR, 0.70 [95% CI, 0.57-0.86], p = 0.0004). The median OS with KEYTRUDA was 10.3 months (95% CI, 8.0-12.3) versus 7.4 months with chemotherapy (95% CI, 6.1-8.1). As previously reported, there was no significant improvement in progression-free survival (PFS) between arms (HR, 0.96 [95% CI, 0.79-1.16], p= 0.32). The median PFS was 2.1 months (95% CI, 2.0-2.2) in the KEYTRUDA arm and 3.3 months (95% CI, 2.4-3.5) in the chemotherapy arm. The six-month, 12-month and 18-month PFS rates in the KEYTRUDA arm were 28.8 percent, 17.6 percent and 16.8 percent, respectively; the six-month, 12-month and 18-month PFS rates in the chemotherapy arm were 28.4 percent, 7.9 percent and 3.5 percent, respectively.
Analyses of the secondary endpoints showed a higher ORR with KEYTRUDA compared to chemotherapy. In patients treated with KEYTRUDA, the ORR was 21.1 percent – with a complete response rate of 7.8 percent and a partial response rate of 13.3 percent. In patients treated with chemotherapy, the ORR was 11.0 percent – with a complete response rate of 2.9 percent and a partial response rate of 8.1 percent. The median duration of response had not been reached in the KEYTRUDA (pembrolizumab) arm (range: 1.6+-20.7+) and was 4.4 months in the chemotherapy arm (range: 1.4+-20.3+).
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. Grade 1-2 treatment-related adverse events in the KEYTRUDA arm included anemia, asthenia, constipation, decreased appetite, diarrhea, fatigue, nausea, peripheral neuropathy, peripheral sensory neuropathy and pruritus. Grade 3-5 treatment-related adverse events in the KEYTRUDA arm included anemia, asthenia, decreased neutrophils, diarrhea, fatigue, nausea and pruritus. Grade 3-5 immune-mediated adverse events included adrenal insufficiency, colitis, nephritis, pneumonitis and severe skin reaction.
Data in First-Line Cisplatin-Ineligible Patients, KEYNOTE-052 (Abstract #4502)
KEYNOTE-052 is a multicenter, open-label, single-arm phase 2 trial, investigating KEYTRUDA in 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy (additional details on the trial design are provided below). Findings to be presented at ASCO, which include the full study population and longer follow-up, show that in the first-line treatment setting many patients with cisplatin-ineligible advanced urothelial carcinoma treated with KEYTRUDA continue to experience complete or partial responses.
In the full study population (n=370), the efficacy analysis showed an ORR of 29 percent (95% CI, 25-34) – with a complete response rate of seven percent (95% CI, 5-10) and a partial response rate of 22 percent (95% CI, 18-27). At the time of analysis, 67 percent of responses were ongoing – of which 82 percent had lasted six months or longer. The median duration of response had not been reached at the time of analysis (95% CI, 12 months-not reached).
The study included a training set (the first 100 patients enrolled), which was used to identify the CPS cut-point for PD-L1 expression, and a validation set (which includes all subsequent 270 evaluable patients) intended to validate the combined positive score (CPS) cut-point. Of the 270 patients in the validation set, in patients with PD-L1 expression of less than 10 percent (CPS <10%), the ORR was 23 percent (95% CI, 17-29), with a complete response rate of three percent (95% CI, 1-6) and a partial response rate of 20 percent (95% CI, 15-27); in patients expressing PD-L1 equal to or greater than 10 percent (CPS ≥10%), the ORR was 51 percent (95% CI, 40-63), with a complete response rate of 18 percent (95% CI, 10-28) and a partial response rate of 34 percent (95% CI, 24-45).
The safety profile of KEYTRUDA was consistent with that observed in previously reported studies. The treatment-related adverse events (any grade occurring in 5% or more of patients [n=370] in descending order) were fatigue (18%), pruritus (17%), rash (12%), decreased appetite (10%), hypothyroidism (10%), diarrhea (9%), and nausea (8%). Grade 3-5 treatment-related adverse events observed (occurring in 3 or more of patients) were fatigue (2%), colitis (2%), muscle weakness (1%), alkaline phosphatase increase (1%), diarrhea (1%), pneumonitis (1%), AST increase (1%), asthenia (1%), hepatitis (1%), and ALT increase (1%). Grade 3-5 immune-mediated adverse events included: adrenal insufficiency, colitis, dermatitis bullous, diabetic ketoacidosis, hepatitis, myocarditis, pneumonitis, thyroiditis, type 1 diabetes mellitus, tubulointerstitial nephritis and rash.
About the KEYNOTE-045 and KEYNOTE-052 Studies
KEYNOTE-045 is a multicenter, randomized, active-controlled, phase 3 trial, investigating KEYTRUDA (pembrolizumab) in 542 patients with locally advanced or metastatic urothelial carcinoma with disease progression on or after platinum-containing chemotherapy. Patients were randomized to receive either KEYTRUDA 200 mg every three weeks (n=270) or investigator’s choice of any of the following chemotherapy regimens, all given intravenously, every three weeks (n=272): paclitaxel 175 mg/m2 (n=84), docetaxel 75 mg/m2 (n=84), or vinflunine 320 mg/m2 (n=87). Treatment continued until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months. The primary endpoints were OS and PFS, as assessed by blinded independent central review (BICR) per RECIST (Response Evaluation Criteria in Solid Tumors) v1.1; additional efficacy outcome measures included ORR, as assessed by BICR per RECIST 1.1, and duration of response. Efficacy was assessed in all patients, as well as in patients with PD-L1 expression – as determined by a CPS of equal to or greater than 10 percent (CPS ≥10%) (KEYTRUDA arm: n=74/270; chemotherapy arm; n=90/272).
KEYNOTE-052 is a multicenter, open-label, single-arm phase 2 trial, investigating KEYTRUDA in 370 patients with locally advanced or metastatic urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy. Patients received KEYTRUDA at a dose of 200 mg every three weeks until unacceptable toxicity or disease progression; patients without disease progression could be treated for up to 24 months. The study included a training set (the first 100 patients enrolled), which was used to identify the CPS cut-point for PD-L1 expression, and a validation set, which includes all subsequent 270 evaluable patients and will be used to validate the CPS cut-point. The primary endpoints include ORR in all patients enrolled in the study (total study population) and in patients with PD-L1 positive tumors (expression of one percent or more); secondary endpoints include duration of response, PFS and OS. Tumor response was measured according to RECIST v1.1 by central imaging vendor review.
About KEYTRUDA ® (pembrolizumab) Injection
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.
Studies of KEYTRUDA – from the largest immuno-oncology program in the industry with more than 500 trials – include a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand factors that predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including the exploration of several different biomarkers across a broad range of tumors.
KEYTRUDA is administered as an intravenous infusion over 30 minutes every three weeks for the approved indications. KEYTRUDA for injection is supplied in a 100 mg single-dose vial.
KEYTRUDA (pembrolizumab) Indications and Dosing
Melanoma
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.
Lung Cancer
KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
KEYTRUDA, as a single agent, is also 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.
KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
In metastatic NSCLC, KEYTRUDA (pembrolizumab) is administered at a fixed dose of 200 mg 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 pemetrexed and carboplatin.
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 is administered at a fixed dose of 200 mg 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 three 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 is administered at a fixed dose of 200 mg 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 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 who are not eligible for cisplatin-containing chemotherapy. 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 also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma 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 (pembrolizumab) is administered at a fixed dose of 200 mg 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 is administered at a fixed dose of 200 mg 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 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
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.
As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program that includes more than 500 clinical trials evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic 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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