Findings Support Initiation of Phase 3 Pivotal Study (KEYNOTE-204) Evaluating KEYTRUDA Versus Brentuximab Vedotin in Relapsed or Refractory cHL
KENILWORTH, NJ, USA I June 6, 2016 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first-time presentation of findings from KEYNOTE-087, the phase 2 study investigating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, as a monotherapy in patients with relapsed or refractory classical Hodgkin lymphoma (cHL). These data will be presented today at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from 8:00 – 11:30 a.m. CDT (Location: Hall A) and in a poster discussion from 1:15 – 2:45 p.m. CDT (Location: E354b) (Abstract #7555).
Results included an analysis of outcome measurements from the study’s three patient cohorts: patients whose disease progressed following an autologous stem cell transplantation and subsequent treatment with brentuximab vedotin, an antibody drug conjugate (Cohort 1); patients who failed salvage chemotherapy and were ineligible for a transplant and whose disease progressed following treatment with brentuximab vedotin (Cohort 2); and patients whose disease progressed after transplant and who did not receive brentuximab vedotin after transplant (Cohort 3). Data showed that the overall response rate (ORR) was more than 70 percent across all three cohorts with the highest ORR, at 83 percent, observed in Cohort 2. Results also included an analysis of patients with primary refractory disease, defined as failure to achieve complete or partial response to first-line treatment. In this patient population, the ORR (by investigator review) was 78 percent. Additionally, 90 to 93 percent of patients experienced a reduction in tumor size across all three cohorts.
“Recurrence of Hodgkin lymphoma occurs in almost half of patients following autologous stem cell transplantation, and the prognosis for patients relapsing or refractory to second-line chemotherapy and transplant is particularly poor, which means there is a significant need to identify therapeutic options that provide meaningful clinical benefit,” said Dr. Craig Moskowitz, clinical director, division of hematologic oncology, Memorial Sloan Kettering Cancer Center. “These early data are encouraging, as they demonstrate high response rates – up to 83 percent – with pembrolizumab in heavily pre-treated patients.”
Data from KEYNOTE-087 supported the recent Breakthrough Therapy Designation granted to KEYTRUDA (pembrolizumab) by the U.S. Food and Drug Administration (FDA) for this type of blood cancer. Additionally, findings from this study support the continued development of KEYTRUDA in patients with cHL, including a phase 3 registration-enabling study (KEYNOTE-204) designed to evaluate monotherapy KEYTRUDA versus brentuximab vedotin in patients with relapsed or refractory cHL.
“Our extensive clinical development program is studying KEYTRUDA in a broad range of solid and blood cancers – including classical Hodgkin lymphoma, where there remains a significant unmet need for patients who do not respond to or relapse following initial treatment,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “These exciting data from KEYNOTE-087 reinforce the potential of KEYTRUDA in hematologic cancers and further invigorate our commitment to improving outcomes across a variety of blood cancers.”
Results presented at ASCO were based on an analysis of 90 patients across three study cohorts. These data showed (per investigator review):
- In Cohort 1 (progressed after transplant and subsequent brentuximab vedotin treatment; n=30), ORR was 73 percent (95% CI, 54-88) – with complete responses in 27 percent (95% CI, 12-46) and partial responses in 47 percent (95% CI, 28-66) of patients. Seventeen percent of patients had stable disease (95% CI, 6-35) and 10 percent of patients had progressive disease (95% CI, 2-27).
- In Cohort 2 (progressed following salvage chemotherapy, transplant-ineligible, and progressed following brentuximab vedotin treatment; n=30), ORR was 83 percent (95% CI, 65-94) – with complete responses in 30 percent (95% CI, 15-49) and partial responses in 53 percent (95% CI, 34-72) of patients. Seven percent of patients had stable disease (95% CI, 1-22) and 7 percent of patients had progressive disease (95% CI, 1-22).
- In Cohort 3 (progressed after transplant and not treated with brentuximab vedotin after transplant; n=30), ORR was 73 percent (95% CI, 54-88) – with complete responses in 30 percent (95% CI, 15-49) and partial responses in 43 percent of patients (95% CI, 26-63). Thirteen percent of patients had stable disease (95% CI, 4-31) and 13 percent of patients had progressive disease (95% CI, 4-31).
In patients with primary refractory disease (n=37), ORR was 78 percent (95% CI, 62-90) – with complete responses in 35 percent (95% CI, 20-53) and partial responses in 43 percent (95% CI, 27-61) of patients. Eleven percent of patients had stable disease (95% CI, 3-25) and 8 percent of patients had progressive disease (95% CI, 2-22).
The safety profile of KEYTRUDA (pembrolizumab) was consistent with that observed in previously reported studies. Grade 3-4 treatment-related adverse events were observed in 4 percent of patients and included neutropenia (n=1), increased amylase (n=1), cytokine release syndrome (n=1), herpes zoster (n=1), increased lipase (n=1), lichenoid dermatosis (n=1), colitis (n=1), and diarrhea (n=1). Two patients discontinued due to treatment-related adverse events (Grade 2 infusion-related reaction and Grade 2 pneumonitis; both Cohort 2). The immune-mediated adverse events (any grade) were rash (n=4, all Grade 1), pneumonitis (n=2, both Grade 2), and colitis (n=1, Grade 3). There were no treatment-related deaths.
The KEYTRUDA clinical development program includes more than 30 tumor types in more than 270 clinical trials, including more than 100 trials that combine KEYTRUDA with other cancer treatments. For hematologic malignancies specifically, Merck is conducting a broad immuno-oncology clinical development program. To date, the program is assessing the role of monotherapy and combination regimens with KEYTRUDA across a variety of hematologic malignancies including leukemia, lymphomas, and myeloma, and includes five registration-enabling studies.
About KEYNOTE-087
KEYNOTE-087 is a multicenter, open-label, multi-cohort, activity-estimating phase 2 trial evaluating KEYTRUDA (200 mg fixed dose every three weeks) monotherapy in patients with relapsed or refractory cHL across three cohorts. The primary endpoints include overall safety, tolerability, and ORR (per central review); secondary endpoints include ORR (per investigator review), progression-free survival (PFS), and overall survival (OS). The patient cohorts are intended to assess the outcome measures in patients whose disease progressed following an autologous stem cell transplantation and subsequent treatment with brentuximab vedotin, an antibody drug conjugate (Cohort 1); patients who failed salvage chemotherapy and were ineligible for a transplant and whose disease progressed following treatment with brentuximab vedotin (Cohort 2); and patients whose disease progressed after transplant and who did not receive brentuximab vedotin after transplant (Cohort 3).
About KEYTRUDA® (pembrolizumab) Injection 100 mg
KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA 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.
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is also indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 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. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every three weeks for the approved indications.
Selected Important Safety Information for KEYTRUDA® (pembrolizumab)
Immune-mediated pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients with NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
Immune-mediated colitis occurred in 31 (2%) of 1567 patients with melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis. Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.
Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Hypophysitis occurred in 13 (0.8%) of 1567 patients with melanoma, including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis. Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.
Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma, including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3 (0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.
Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in 7 (0.4%) of 1567 patients with melanoma including, Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
The following clinically significant, immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 1567 patients with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients with NSCLC: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.
Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.
In Trial 6, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA (pembrolizumab) vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.
In Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculo-papular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.
KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients with NSCLC. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).
No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA.
It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.
Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.
Our Focus on Cancer
Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck Oncology, 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 270 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 125 years, Merck has been a global health care leader working to help the world be well. Merck is known as MSD outside the United States and Canada. 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. For more information, visit www.merck.com and connect with us on Twitter, Facebook, YouTube and LinkedIn.
SOURCE: Merck
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Findings Support Initiation of Phase 3 Pivotal Study (KEYNOTE-204) Evaluating KEYTRUDA Versus Brentuximab Vedotin in Relapsed or Refractory cHL
KENILWORTH, NJ, USA I June 6, 2016 I Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the first-time presentation of findings from KEYNOTE-087, the phase 2 study investigating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, as a monotherapy in patients with relapsed or refractory classical Hodgkin lymphoma (cHL). These data will be presented today at the 52nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago from 8:00 – 11:30 a.m. CDT (Location: Hall A) and in a poster discussion from 1:15 – 2:45 p.m. CDT (Location: E354b) (Abstract #7555).
Results included an analysis of outcome measurements from the study’s three patient cohorts: patients whose disease progressed following an autologous stem cell transplantation and subsequent treatment with brentuximab vedotin, an antibody drug conjugate (Cohort 1); patients who failed salvage chemotherapy and were ineligible for a transplant and whose disease progressed following treatment with brentuximab vedotin (Cohort 2); and patients whose disease progressed after transplant and who did not receive brentuximab vedotin after transplant (Cohort 3). Data showed that the overall response rate (ORR) was more than 70 percent across all three cohorts with the highest ORR, at 83 percent, observed in Cohort 2. Results also included an analysis of patients with primary refractory disease, defined as failure to achieve complete or partial response to first-line treatment. In this patient population, the ORR (by investigator review) was 78 percent. Additionally, 90 to 93 percent of patients experienced a reduction in tumor size across all three cohorts.
“Recurrence of Hodgkin lymphoma occurs in almost half of patients following autologous stem cell transplantation, and the prognosis for patients relapsing or refractory to second-line chemotherapy and transplant is particularly poor, which means there is a significant need to identify therapeutic options that provide meaningful clinical benefit,” said Dr. Craig Moskowitz, clinical director, division of hematologic oncology, Memorial Sloan Kettering Cancer Center. “These early data are encouraging, as they demonstrate high response rates – up to 83 percent – with pembrolizumab in heavily pre-treated patients.”
Data from KEYNOTE-087 supported the recent Breakthrough Therapy Designation granted to KEYTRUDA (pembrolizumab) by the U.S. Food and Drug Administration (FDA) for this type of blood cancer. Additionally, findings from this study support the continued development of KEYTRUDA in patients with cHL, including a phase 3 registration-enabling study (KEYNOTE-204) designed to evaluate monotherapy KEYTRUDA versus brentuximab vedotin in patients with relapsed or refractory cHL.
“Our extensive clinical development program is studying KEYTRUDA in a broad range of solid and blood cancers – including classical Hodgkin lymphoma, where there remains a significant unmet need for patients who do not respond to or relapse following initial treatment,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “These exciting data from KEYNOTE-087 reinforce the potential of KEYTRUDA in hematologic cancers and further invigorate our commitment to improving outcomes across a variety of blood cancers.”
Results presented at ASCO were based on an analysis of 90 patients across three study cohorts. These data showed (per investigator review):
- In Cohort 1 (progressed after transplant and subsequent brentuximab vedotin treatment; n=30), ORR was 73 percent (95% CI, 54-88) – with complete responses in 27 percent (95% CI, 12-46) and partial responses in 47 percent (95% CI, 28-66) of patients. Seventeen percent of patients had stable disease (95% CI, 6-35) and 10 percent of patients had progressive disease (95% CI, 2-27).
- In Cohort 2 (progressed following salvage chemotherapy, transplant-ineligible, and progressed following brentuximab vedotin treatment; n=30), ORR was 83 percent (95% CI, 65-94) – with complete responses in 30 percent (95% CI, 15-49) and partial responses in 53 percent (95% CI, 34-72) of patients. Seven percent of patients had stable disease (95% CI, 1-22) and 7 percent of patients had progressive disease (95% CI, 1-22).
- In Cohort 3 (progressed after transplant and not treated with brentuximab vedotin after transplant; n=30), ORR was 73 percent (95% CI, 54-88) – with complete responses in 30 percent (95% CI, 15-49) and partial responses in 43 percent of patients (95% CI, 26-63). Thirteen percent of patients had stable disease (95% CI, 4-31) and 13 percent of patients had progressive disease (95% CI, 4-31).
In patients with primary refractory disease (n=37), ORR was 78 percent (95% CI, 62-90) – with complete responses in 35 percent (95% CI, 20-53) and partial responses in 43 percent (95% CI, 27-61) of patients. Eleven percent of patients had stable disease (95% CI, 3-25) and 8 percent of patients had progressive disease (95% CI, 2-22).
The safety profile of KEYTRUDA (pembrolizumab) was consistent with that observed in previously reported studies. Grade 3-4 treatment-related adverse events were observed in 4 percent of patients and included neutropenia (n=1), increased amylase (n=1), cytokine release syndrome (n=1), herpes zoster (n=1), increased lipase (n=1), lichenoid dermatosis (n=1), colitis (n=1), and diarrhea (n=1). Two patients discontinued due to treatment-related adverse events (Grade 2 infusion-related reaction and Grade 2 pneumonitis; both Cohort 2). The immune-mediated adverse events (any grade) were rash (n=4, all Grade 1), pneumonitis (n=2, both Grade 2), and colitis (n=1, Grade 3). There were no treatment-related deaths.
The KEYTRUDA clinical development program includes more than 30 tumor types in more than 270 clinical trials, including more than 100 trials that combine KEYTRUDA with other cancer treatments. For hematologic malignancies specifically, Merck is conducting a broad immuno-oncology clinical development program. To date, the program is assessing the role of monotherapy and combination regimens with KEYTRUDA across a variety of hematologic malignancies including leukemia, lymphomas, and myeloma, and includes five registration-enabling studies.
About KEYNOTE-087
KEYNOTE-087 is a multicenter, open-label, multi-cohort, activity-estimating phase 2 trial evaluating KEYTRUDA (200 mg fixed dose every three weeks) monotherapy in patients with relapsed or refractory cHL across three cohorts. The primary endpoints include overall safety, tolerability, and ORR (per central review); secondary endpoints include ORR (per investigator review), progression-free survival (PFS), and overall survival (OS). The patient cohorts are intended to assess the outcome measures in patients whose disease progressed following an autologous stem cell transplantation and subsequent treatment with brentuximab vedotin, an antibody drug conjugate (Cohort 1); patients who failed salvage chemotherapy and were ineligible for a transplant and whose disease progressed following treatment with brentuximab vedotin (Cohort 2); and patients whose disease progressed after transplant and who did not receive brentuximab vedotin after transplant (Cohort 3).
About KEYTRUDA® (pembrolizumab) Injection 100 mg
KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA 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.
KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.
KEYTRUDA is also indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 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. This indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.
KEYTRUDA is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every three weeks for the approved indications.
Selected Important Safety Information for KEYTRUDA® (pembrolizumab)
Immune-mediated pneumonitis, including fatal cases, occurred in patients receiving KEYTRUDA. Pneumonitis occurred in 32 (2.0%) of 1567 patients with melanoma, including Grade 1 (0.8%), 2 (0.8%), and 3 (0.4%) pneumonitis. Pneumonitis occurred in 19 (3.5%) of 550 patients with NSCLC, including Grade 2 (1.1%), 3 (1.3%), 4 (0.4%), or 5 (0.2%) pneumonitis and more frequently in patients with a history of asthma/chronic obstructive pulmonary disease (5.4%) or prior thoracic radiation (6.0%). Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.
Immune-mediated colitis occurred in 31 (2%) of 1567 patients with melanoma, including Grade 2 (0.5%), 3 (1.1%), and 4 (0.1%) colitis. Immune-mediated colitis occurred in 4 (0.7%) of 550 patients with NSCLC, including Grade 2 (0.2%) or 3 (0.4%) colitis. Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA (pembrolizumab) for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.
Immune-mediated hepatitis occurred in patients receiving KEYTRUDA. Hepatitis occurred in 16 (1%) of 1567 patients with melanoma, including Grade 2 (0.1%), 3 (0.7%), and 4 (0.1%) hepatitis. Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.
Hypophysitis occurred in 13 (0.8%) of 1567 patients with melanoma, including Grade 2 (0.3%), 3 (0.3%), and 4 (0.1%) hypophysitis. Hypophysitis occurred in 1 (0.2 %) of 550 patients with NSCLC, which was Grade 3 in severity. Monitor patients for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency). Administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2; withhold or discontinue for Grade 3 or 4 hypophysitis.
Hyperthyroidism occurred in 51 (3.3%) of 1567 patients with melanoma, including Grade 2 (0.6%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 127 (8.1%) of 1567 patients with melanoma, including Grade 3 (0.1%) hypothyroidism. Hyperthyroidism occurred in 10 (1.8%) of 550 patients with NSCLC, including Grade 2 (0.7%) or 3 (0.3%) hyperthyroidism. Hypothyroidism occurred in 38 (6.9%) of 550 patients with NSCLC, including Grade 2 (5.5%) or 3 (0.2%) hypothyroidism. Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders. Administer replacement hormones for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.
Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 3 (0.1%) of 2117 patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer anti-hyperglycemics in patients with severe hyperglycemia.
Immune-mediated nephritis occurred in patients receiving KEYTRUDA. Nephritis occurred in 7 (0.4%) of 1567 patients with melanoma including, Grade 2 (0.2%), 3 (0.2%), and 4 (0.1%) nephritis. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA (pembrolizumab) for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 nephritis.
Other clinically important immune-mediated adverse reactions can occur. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.
The following clinically significant, immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 1567 patients with melanoma: arthritis (1.6%), exfoliative dermatitis, bullous pemphigoid, uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. The following clinically significant, immune-mediated adverse reactions occurred in less than 1% of 550 patients with NSCLC: rash, vasculitis, hemolytic anemia, serum sickness, and myasthenia gravis.
Severe and life-threatening infusion-related reactions have been reported in 3 (0.1%) of 2117 patients. Monitor patients for signs and symptoms of infusion related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.
Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. If used during pregnancy, or if the patient becomes pregnant during treatment, apprise the patient of the potential hazard to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 4 months after the last dose of KEYTRUDA.
In Trial 6, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). Adverse reactions leading to interruption of KEYTRUDA occurred in 21% of patients; the most common (≥1%) was diarrhea (2.5%). The most common adverse reactions with KEYTRUDA (pembrolizumab) vs ipilimumab were fatigue (28% vs 28%), diarrhea (26% with KEYTRUDA), rash (24% vs 23%), and nausea (21% with KEYTRUDA). Corresponding incidence rates are listed for ipilimumab only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.
In Trial 2, KEYTRUDA was discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (≥1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). Adverse reactions leading to interruption of KEYTRUDA occurred in 14% of patients; the most common (≥1%) were dyspnea (1%), diarrhea (1%), and maculo-papular rash (1%). The most common adverse reactions with KEYTRUDA vs chemotherapy were fatigue (43% with KEYTRUDA), pruritus (28% vs 8%), rash (24% vs 8%), constipation (22% vs 20%), nausea (22% with KEYTRUDA), diarrhea (20% vs 20%), and decreased appetite (20% with KEYTRUDA). Corresponding incidence rates are listed for chemotherapy only for those adverse reactions that occurred at the same or lower rate than with KEYTRUDA.
KEYTRUDA was discontinued due to adverse reactions in 14% of 550 patients with NSCLC. Serious adverse reactions occurred in 38% of patients. The most frequent serious adverse reactions reported at least 2% of patients were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis. The most common adverse reactions (reported in at least 20% of patients) were fatigue (44%), cough (29%), decreased appetite (25%), and dyspnea (23%).
No formal pharmacokinetic drug interaction studies have been conducted with KEYTRUDA.
It is not known whether KEYTRUDA is excreted in human milk. Because many drugs are excreted in human milk, instruct women to discontinue nursing during treatment with KEYTRUDA and for 4 months after the final dose.
Safety and effectiveness of KEYTRUDA have not been established in pediatric patients.
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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 270 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.
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SOURCE: Merck
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