Progression-Free Survival Data from ECHO-202 Trial of Incyte’s Epacadostat in Combination with Merck’s
KEYTRUDA ® (pembrolizumab) Underscore Durability of Response in Patients with Advanced
Melanoma
Updated Data to be Presented at ESMO 2017 Congress
Incyte Corporation (Nasdaq:INCY) and Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced
updated data from the ongoing Phase 1/2 ECHO-202 trial (KEYNOTE-037) evaluating epacadostat, Incyte’s selective IDO1 enzyme
inhibitor, in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with advanced melanoma.
Among all patients with advanced melanoma, including treatment-naïve and treatment-experienced, data showed an overall response
rate (ORR) of 56 percent (n=35/63) in patients treated with the combination of epacadostat and KEYTRUDA; median progression-free
survival (PFS) was 12.4 months, with PFS rates of 65 percent at six months, 52 percent at 12 months, and 49 percent at 18 months.
Results were generally consistent across dosing schedules of epacadostat combined with KEYTRUDA, including epacadostat 100 mg BID,
the epacadostat dose being studied in the Phase 3 ECHO-301 trial.
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These results will be presented at the European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain, in an oral
presentation on Saturday, September 9 from 3-3:15 pm CEST (Location: Madrid Auditorium) (Abstract #1214O).
“The updated results of the ECHO-202 trial support earlier published findings, and continue to suggest that the novel
immunotherapy combination of epacadostat plus KEYTRUDA has the potential to offer a favorable efficacy and safety profile for the
treatment of patients with advanced melanoma,” said Omid Hamid, M.D., Chief of Translational Research and Immuno-Oncology and
Director of Melanoma Therapeutics, The Angeles Clinic and Research Institute, Los Angeles, California. “Data have shown that
combination immunotherapy can offer higher response rates and improved progression-free survival. These results show that this
combination has demonstrated increased and durable response rates and improved progression-free survival, compared to what we would
expect from KEYTRUDA alone, without sacrificing safety.”
Key Findings from the ECHO-202 (KEYNOTE-037) Melanoma Cohort
Data at ESMO (as of June 9, 2017) show an ORR of 56 percent among all patients with advanced melanoma treated with the
combination of epacadostat and KEYTRUDA, with a complete response (CR) in nine patients (14%); partial response (PR) in 26 patients
(41%); and stable disease (SD) in 10 patients (16%). Data also show a disease control rate (DCR) of 71 percent (n=45/63). Of the 35
responses to treatment, 30 were ongoing at the time of analysis; the median duration of response was 45 weeks (range: 1+ to
121+).
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ECHO-202 Overall Response Rates (ORR), Disease Control Rates (DCR), Durability of
Response (DoR), and Progression-Free Survival (PFS) in Advanced Melanoma Cohort
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All
Patients
(N=65)
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Treatment-Naïve
(all epacadostat doses)
(N=54)
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Treatment-Naïve
(epacadostat 100 mg BID)
(N=39)
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Per-protocol
evaluable n (%) 1
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n=63 |
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n=53 |
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n=38 |
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ORR |
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35 (56) |
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29 (55) |
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22 (58) |
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9 CR (14)
26 PR (41)
10 SD (16)
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7 CR (13)
22 PR (42)
9 SD (17)
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3 CR (8)
19 PR (50)
6 SD (16)
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DCR |
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45 (71) |
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38 (72) |
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28 (74) |
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18 PD or death (29)
2 not evaluable2
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15 PD or death (28)
1 not evaluable2
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10 PD or death (26)
1 not evaluable2
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DoR |
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30/35 responses
ongoing
Duration of response:
<1+ to 121+ weeks
4/5 patients
completing study
treatment maintained
ongoing response at last
follow-up
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25/29 responses
ongoing
Duration of response:
<1+ to 121+ weeks
3/4 patients completing
study treatment
maintained ongoing
response at last follow-up
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20/22 responses
ongoing
Duration of response:
<1+ to 81+ weeks
1/1 patient completing study
treatment maintained
ongoing response at last
follow-up
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Median PFS,
months
(90% CI)
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12.4
(6.2, 23.8)
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22.8
(6.2, 23.8)
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Not yet reached
(4.2, NR)
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PFS rate,
% (90% CI)
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6-month:
65 (54, 74)
12-month:
52 (40, 63)
18-month:
49 (37, 60)
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6-month:
65 (53, 75)
12-month:
52 (38, 64)
18-month:
52 (38, 64)
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6-month:
64 (49, 76)
12-month:
55 (39, 69)
18-month:
55 (39, 69)
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1. ≥1 post-baseline scan, or discontinuation or death before first post-baseline scan
2. Scan data not documented in the clinical trial database at time of data cutoff
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The most common (≥10 percent) all grade treatment-related adverse events (TRAEs) were rash (46 percent), fatigue (43 percent),
pruritus (29 percent), and arthralgia (17 percent). Grade ≥3 TRAEs were observed in 20 percent of patients; the most common were
increased lipase (6 percent) and rash (5 percent). Four patients (6 percent) discontinued for TRAEs. No treatment-related deaths
occurred. The safety profile was consistent with previously reported Phase 1 findings, as well as the Phase 1/2 safety results in
other tumor cohorts and pooled safety data from this study. In general, the safety profile of the combination was also consistent
with KEYTRUDA (pembrolizumab) monotherapy.
About ECHO-202 (KEYNOTE-037)
The ECHO-202 study (NCT02178722) is evaluating the safety and efficacy of epacadostat, Incyte’s selective IDO1 enzyme inhibitor,
in combination with KEYTRUDA. Patients previously treated with anti-PD-1 or anti-CTLA-4 therapies were excluded from this trial.
Enrollment is complete for the Phase 1 dose escalation (epacadostat 25, 50, 100 mg BID + KEYTRUDA 2 mg/kg IV Q3W and epacadostat
300 mg BID + KEYTRUDA 200 mg IV Q3W) and Phase 1 dose expansion (epacadostat 50, 100, and 300 mg BID + KEYTRUDA 200 mg IV Q3W)
portions of the trial. For more information about ECHO-202, visit https://clinicaltrials.gov/ct2/show/NCT02178722.
About ECHO
The ECHO clinical trial program was established to investigate the efficacy and safety of epacadostat as a core component of
combination therapy in oncology. Ongoing Phase 1 and Phase 2 studies are evaluating epacadostat in combination with PD-1 and PD-L1
inhibitors in a broad range of solid tumor types as well as hematological malignancies. ECHO-301 (NCT02752074), a Phase 3
randomized, double-blind, placebo-controlled study investigating KEYTRUDA in combination with epacadostat or placebo for the
treatment of patients with unresectable or metastatic melanoma, is also ongoing and fully recruited. For more information about the
ECHO clinical trial program, visit www.ECHOClinicalTrials.com.
About Epacadostat (INCB024360)
The immunosuppressive effects of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity on the tumor microenvironment help cancer
cells evade immunosurveillance. Epacadostat is an investigational, highly potent and selective oral inhibitor of the IDO1 enzyme.
In single-arm studies, the combination of epacadostat and immune checkpoint inhibitors has shown proof-of-concept in patients with
unresectable or metastatic melanoma, non-small cell lung cancer, renal cell carcinoma, squamous cell carcinoma of the head and neck
and bladder cancer. In these studies, epacadostat combined with the CTLA-4 inhibitor ipilimumab or the PD-1 inhibitors KEYTRUDA or
nivolumab improved response rates compared with studies of the immune checkpoint inhibitors alone.
Incyte Conference Call Information
Incyte will host an investor conference call and webcast at 17:00 CET (11:00 a.m. ET) on 9 September 2017—the call and webcast
can be accessed via the Events and Presentations tab of the Investor section of www.incyte.com.
To access the conference call on Saturday 9 September 2017, please dial 877-407-3042 for domestic callers or +1-201-389-0864 for
international callers. When prompted, provide the conference identification number, 13667084.
If you are unable to participate, a replay of the conference call will be available for 30 days. The replay dial-in number for
the United States is 877-660-6853 and the dial-in number for international callers is +1-201-612-7415. To access the replay you
will need the conference identification number, 13667084.
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.
Studies of KEYTRUDA (pembrolizumab) – from the largest immuno-oncology program in the industry with more than 550 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 (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 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 (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. 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 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.
Selected Important Safety Information for KEYTRUDA® (pembrolizumab)
KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 94 (3.4%) of 2799 patients
receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%) pneumonitis, and occurred more frequently
in patients with a history of prior thoracic radiation (6.9%) compared to those without (2.9%). 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.
KEYTRUDA (pembrolizumab) can cause immune-mediated colitis. Colitis occurred in 48 (1.7%) of 2799 patients receiving KEYTRUDA,
including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%) colitis. Monitor patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4
colitis.
KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 19 (0.7%) of 2799 patients receiving KEYTRUDA, including
Grade 2 (0.1%), 3 (0.4%), 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.
KEYTRUDA can cause hypophysitis. Hypophysitis occurred in 17 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2
(0.2%), 3 (0.3%), and 4 (<0.1%) hypophysitis. 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.
KEYTRUDA can cause thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96
(3.4%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3 (0.1%) hyperthyroidism. Hypothyroidism occurred in 237
(8.5%) of 2799 patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%) hypothyroidism. The incidence of new or worsening
hypothyroidism was higher in patients with HNSCC, occurring in 28 (15%) of 192 patients with HNSCC, including Grade 3 (0.5%)
hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis.
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.
KEYTRUDA can cause type 1 diabetes mellitus, including diabetic ketoacidosis, which have been reported in 6 (0.2%) of 2799
patients. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Administer insulin for type 1 diabetes, and
withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.
KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 9 (0.3%) of 2799 patients receiving KEYTRUDA, including
Grade 2 (0.1%), 3 (0.1%), 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.
Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal
outcome), exfoliative dermatitis, and bullous pemphigoid can occur. Monitor patients for suspected severe skin reactions and based
on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs and
symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is
confirmed, permanently discontinue KEYTRUDA.
KEYTRUDA can cause other clinically important immune-mediated adverse reactions. These immune-mediated reactions may occur in
any organ system. 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 (pembrolizumab) 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
2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic
anemia, and partial seizures arising in a patient with inflammatory foci in brain parenchyma. In addition, myelitis and myocarditis
were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.
Solid organ transplant rejection has been reported in postmarketing use of KEYTRUDA. Treatment with KEYTRUDA may increase the
risk of rejection in solid organ transplant recipients. Consider the benefit of treatment with KEYTRUDA vs the risk of possible
organ rejection in these patients.
KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have
been reported in 6 (0.2%) of 2799 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.
Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after being treated with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after treatment
with KEYTRUDA on any trial, 6 patients (26%) developed graft-versus-host-disease (GVHD), one of which was fatal, and 2 patients
(9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning, one of which was fatal. Cases of
fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptor–blocking
antibody before transplantation. These complications may occur despite intervening therapy between PD-1 blockade and allogeneic
HSCT. Follow patients closely for early evidence of transplant-related complications such as hyperacute GVHD, severe (Grade 3 to 4)
acute GVHD, steroid-requiring febrile syndrome, hepatic VOD, and other immune-mediated adverse reactions, and intervene
promptly.
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 KEYNOTE-006, 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 vs ipilimumab were fatigue
(28% vs 28%), diarrhea (26% with KEYTRUDA (pembrolizumab)), 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.
KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC. The most common
adverse event resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.8%). Adverse reactions leading to interruption
of KEYTRUDA occurred in 23% of patients; the most common (≥1%) were diarrhea (1%), fatigue (1.3%), pneumonia (1%), liver enzyme
elevation (1.2%), decreased appetite (1.3%), and pneumonitis (1%). The most common adverse reactions (occurring in at least 20% of
patients and at a higher incidence than with docetaxel) were decreased appetite (25% vs 23%), dyspnea (23% vs 20%), and nausea (20%
vs 18%).
When KEYTRUDA was administered in combination with carboplatin and pemetrexed (carbo/pem), KEYTRUDA was discontinued in 10% of
59 patients. The most common adverse reaction resulting in discontinuation of KEYTRUDA (≥2%) was acute kidney injury (3.4%).
Adverse reactions leading to interruption of KEYTRUDA occurred in 39% of patients; the most common (≥2%) were fatigue (8%),
neutrophil count decreased (8%), anemia (5%), dyspnea (3.4%), and pneumonitis (3.4%).The most common adverse reactions (≥20%) with
KEYTRUDA compared to carbo/pem alone were fatigue (71% vs 50%), nausea (68% vs 56%), constipation (51% vs 37%), rash (42% vs 21%),
vomiting (39% vs 27%), dyspnea (39% vs 21%), diarrhea (37% vs 23%), decreased appetite (31% vs 23%), headache (31% vs 16%), cough
(24% vs 18%), dizziness (24% vs 16%), insomnia (24% vs 15%), pruritus (24% vs 4.8%), peripheral edema (22% vs 18%), dysgeusia (20%
vs 11%), alopecia (20% vs 3.2%), upper respiratory tract infection (20% vs 3.2%), and arthralgia (15% vs 24%). This study was not
designed to demonstrate a statistically significant difference in adverse reaction rates for KEYTRUDA as compared to carbo/pem
alone for any specified adverse reaction.
KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45%
of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional
state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (reported in at least 20% of
patients) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar
to those occurring in patients with melanoma or NSCLC, with the exception of increased incidences of facial edema (10% all Grades;
2.1% Grades 3 or 4) and new or worsening hypothyroidism.
KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL, and treatment was interrupted due to adverse
reactions in 26% of patients. Fifteen percent (15%) of patients had an adverse reaction requiring systemic corticosteroid therapy.
Serious adverse reactions occurred in 16% of patients. The most frequent serious adverse reactions (≥1%) included pneumonia,
pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; one from GVHD
after subsequent allogeneic HSCT and one from septic shock. The most common adverse reactions (occurring in ≥20% of patients) were
fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).
In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reactions (in≥20% of patients) were fatigue (38%), musculoskeletal pain (24%),
decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%). Eighteen patients (5%) died from causes other than
disease progression. Five patients (1.4%) who were treated with KEYTRUDA experienced sepsis which led to death, and 3 patients
(0.8%) experienced pneumonia which led to death. Adverse reactions leading to interruption of KEYTRUDA (pembrolizumab) occurred in
22% of patients; the most common (≥1%) were liver enzyme increase, diarrhea, urinary tract infection, acute kidney injury, fatigue,
joint pain, and pneumonia. Serious adverse reactions occurred in 42% of patients, the most frequent (≥2%) of which were urinary
tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis.
In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic
urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%).
Adverse reactions leading to interruption of KEYTRUDA occurred in 20% of patients; the most common (≥1%) were urinary tract
infection (1.5%), diarrhea (1.5%), and colitis (1.1%). The most common adverse reactions (20%) in patients who received KEYTRUDA vs
those who received chemotherapy were fatigue (38% vs 56%), musculoskeletal pain (32% vs 27%), pruritus (23% vs 6%), decreased
appetite (21% vs 21%), nausea (21% vs 29%), and rash (20% vs 13%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated
patients, the most frequent (≥2%) of which were urinary tract infection, pneumonia, anemia, and pneumonitis.
There is limited experience in pediatric patients. Efficacy for pediatric patients was extrapolated from the results in the
adult cHL population. In a study of 40 pediatric patients with advanced melanoma, PD-L1–positive advanced, relapsed, or refractory
solid tumors or lymphoma, patients were treated with KEYTRUDA for a median of 43 days (range 1-414 days), with 24 patients (60%)
receiving treatment for 42 days or more. The safety profile in pediatric patients was similar to that seen in adults treated with
KEYTRUDA. Toxicities that occurred at a higher rate (≥15% difference) in these patients when compared to adults under 65 years of
age were fatigue (45%), vomiting (38%), abdominal pain (28%), hypertransaminasemia (28%), and hyponatremia (18%).
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.
About Incyte
Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical company focused on the discovery, development and
commercialization of proprietary therapeutics. For additional information on Incyte, please visit the Company’s website at www.incyte.com.
Follow @Incyte on Twitter at https://twitter.com/Incyte.
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.
Forward-Looking Statement of Incyte Corporation
Except for the historical information set forth herein, the matters set forth in this press release, including statements
regarding whether the combination of epacadostat plus KEYTRUDA will offer a safe and effective treatment for patients with advanced
melanoma and the phase 3 trial of epacadostat in combination with KEYTRUDA for the treatment of melanoma, contain predictions,
estimates and other forward-looking statements. These forward-looking statements are based on the Company’s current expectations
and subject to risks and uncertainties that may cause actual results to differ materially, including unanticipated developments and
the risks related to the efficacy or safety of the Company’s development pipeline, the results of further research and development,
the high degree of risk and uncertainty associated with drug development, clinical trials and regulatory approval processes, other
market or economic factors and competitive and technological advances; and other risks detailed from time to time in the Company’s
reports filed with the Securities and Exchange Commission, including its Form 10-Q for the quarter ended June 30, 2017. Incyte
disclaims any intent or obligation to update these forward-looking statements.
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within
the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There
can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that
they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize,
actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors,
including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care
legislation in the United States and internationally; global trends toward health care cost containment; technological advances,
new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory
approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial
instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other
protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause results to differ materially from those described in the
forward-looking statements can be found in the company’s 2016 Annual Report on Form 10-K and the company’s other filings with the
Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Please see Prescribing Information for KEYTRUDA (pembrolizumab) at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_pi.pdf and Patient Information/Medication
Guide for KEYTRUDA at http://www.merck.com/product/usa/pi_circulars/k/keytruda/keytruda_mg.pdf .
Incyte Contacts
Media
Catalina Loveman, +1 302-498-6171
or
Investors
Michael Booth, DPhil, +1 302-498-5914
or
Merck Contacts
Media
Pamela Eisele, +1 267-305-3558
Elizabeth Sell, +1 267-305-3877
or
Investors
Teri Loxam, +1 908-740-1986
Amy Klug, +1 908-740-1898
View source version on businesswire.com: http://www.businesswire.com/news/home/20170909005016/en/