Merck’s KEYTRUDA® (pembrolizumab) Superior to Standard of Care Chemotherapy in Patients with MSI-H Colorectal Cancer

KEYTRUDA Monotherapy Significantly Reduced Risk of Disease Progression or Death by 40% and More Than Doubled Median Progression-Free Survival Versus Chemotherapy

KEYNOTE-177 is the First Positive Head-to-Head Phase 3 Trial of a Single-Agent, Anti-PD-1 Therapy Compared to Chemotherapy as First-Line Treatment for Patients with MSI-H Colorectal Cancer

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced the first presentation of results from KEYNOTE-177, a Phase 3 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, for the first-line treatment of patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) unresectable or metastatic colorectal cancer. In this pivotal study, KEYTRUDA monotherapy significantly reduced the risk of disease progression or death by 40% (HR=0.60 [95% CI, 0.45-0.80; p=0.0002]) and showed a median progression-free survival (PFS) of 16.5 months compared with 8.2 months for patients treated with chemotherapy (investigator’s choice of mFOLFOX6 or FOLFIRI, with or without bevacizumab or cetuximab), a current standard of care in this patient population. As previously announced, the study will continue without changes to evaluate overall survival (OS), the other dual primary endpoint. These results were selected for presentation on Sunday, May 31, 2020 in the plenary session of the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA4).

“For many years, the standard of care for the first-line treatment of patients with MSI-H colorectal cancer has been the combination of mFOLFOX6 plus bevacizumab. This is the first time a single-agent, anti-PD-1 therapy demonstrated a superior, statistically significant and clinically meaningful improvement in progression-free survival compared to chemotherapy for these patients,” said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “There is an unmet need for new treatment options in the first-line setting that may provide sustained, long-term improvements in outcomes for patients with MSI-H colorectal cancer. We are grateful to have the opportunity to present these practice-changing findings at the plenary session of this year’s ASCO.”

“KEYTRUDA monotherapy significantly reduced the risk of disease progression or death by 40% versus standard of care chemotherapy, with fewer treatment-related adverse events observed, in patients with MSI-H metastatic colorectal cancer. KEYTRUDA also demonstrated a long-term, durable response that lasted over two years for those who responded to treatment,” said Thierry Andre, MD, professor of medical oncology, Sorbonne University, and Head of the Medical Oncology Department in St. Antoine Hospital, Assistance Publique Hôpitaux de Paris. “Data from KEYNOTE-177 show that KEYTRUDA monotherapy has the potential to become the new standard of care for first-line treatment of patients with MSI-H metastatic colorectal cancer.”

In May 2017, KEYTRUDA became the first cancer therapy approved by the U.S. Food and Drug Administration for use based on a biomarker, regardless of tumor type, in previously treated patients with MSI-H or dMMR solid tumors.

As announced, more than 80 abstracts in nearly 20 types of solid tumors and blood cancers will be presented from Merck’s broad oncology portfolio and investigational pipeline at ASCO. A compendium of presentations and posters of Merck-led studies will be posted by Merck on Friday, May 29 at 8 a.m. ET. Follow Merck on Twitter via @Merck and keep up to date with ASCO news and updates by using the hashtag #ASCO20.

KEYNOTE-177 Study Design and Additional Data (Abstract #LBA4)

KEYNOTE-177 is a randomized, open-label, Phase 3 trial evaluating KEYTRUDA monotherapy versus standard of care chemotherapy for the first-line treatment of patients with MSI-H or dMMR metastatic colorectal cancer (ClinicalTrials.gov, NCT02563002). The dual primary endpoints are PFS and OS. The study enrolled 307 patients, who were randomized to receive either KEYTRUDA (200 mg intravenously on Day 1 of each three-week cycle for up to 35 cycles) or investigator’s choice of one of the following chemotherapy-based regimens: mFOLFOX6; mFOLFOX6 plus bevacizumab (5 mg/kg IV on Day 1 of each two-week cycle); mFOLFOX6 plus cetuximab (400 mg/m2 IV, then 250 mg/m2 weekly in each two-week cycle); FOLFIRI; FOLFIRI plus bevacizumab (5 mg/kg IV on Day 1 of each two-week cycle); or FOLFIRI plus cetuximab (400 mg/m2 IV, then 250 mg/m2 weekly in each two-week cycle).

In this study, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in PFS (HR=0.60 [95% CI, 0.45-0.80; p=0.0002]) and showed a median PFS of 16.5 months compared with 8.2 months for patients treated with chemotherapy. The two-year PFS rate was 48% with KEYTRUDA versus 19% with chemotherapy. The ORR was 43.8% with KEYTRUDA versus 33.1% with chemotherapy, with a complete response observed in 11.1% and 3.9% of patients, respectively; partial responses were observed in 32.7% and 29.2% of patients, respectively. Median duration of response was not reached with KEYTRUDA (range, 2.3+ to 41.4+) versus 10.6 months with chemotherapy (range, 2.8 to 37.5+). Additionally, 83% of patients had durable responses lasting at least two years with KEYTRUDA versus 35% with chemotherapy. In the study, 59% of patients in the intent-to-treat population received subsequent anti-PD-1/PD-L1 therapy after discontinuing study treatment in the chemotherapy arm.

The safety profile of KEYTRUDA demonstrated a lower incidence of Grade ≥3 treatment-related adverse events (AEs) versus chemotherapy (22% versus 66%, respectively), and no new toxicities were observed. Immune-mediated AEs and infusion reactions occurred in 31% of patients receiving KEYTRUDA and 13% of patients receiving chemotherapy. The most commonly reported immune-mediated AEs were hypothyroidism (12%) and colitis (7%) with KEYTRUDA, and infusion reactions (8%) with chemotherapy.

Merck Investor Event

Merck will hold a virtual investor event in conjunction with the ASCO Annual Meeting on Tuesday, June 2 at 2 p.m. ET. Details will be provided at a date closer to the event at http://investors.merck.com/home/default.aspx.

About Microsatellite Instability High (MSI-H)

Microsatellite instability (or MSI) is defined by the National Cancer Institute as a change that occurs in the DNA of certain cells (such as tumor cells) in which the number of repeats of microsatellites (short, repeated sequences of DNA) is different from the number of repeats that was in the DNA when it was inherited. The cause of MSI may be a defect in the ability to repair mistakes made when DNA is copied in the cell. This defect is also referred to as mismatch repair deficiency (dMMR). It is estimated that approximately 5-15% of colorectal cancer patients have tumors that score as either MSI-H or dMMR when testing is performed.

About Colorectal Cancer

Colorectal cancer starts in the colon or the rectum, and these cancers are referred to as colon cancer and rectal cancer depending on where the cancer starts. Colorectal cancer often begins with growths on the inner lining of the colon or rectum called polyps, which can change into cancer over time. Colorectal cancer is the third most commonly diagnosed cancer and the second most common cause of cancer-related death worldwide. It is estimated there were nearly 850,000 new cases of colorectal cancer and more than 880,000 deaths from the disease globally in 2018. In the United States, it is estimated there will be nearly 105,000 new cases of colon cancer and more than 43,000 new cases of rectal cancer, resulting in more than 53,000 deaths from colorectal cancer in 2020. The five-year survival rates for advanced/metastatic colon cancer and rectal cancer (stage IV) are estimated to be 14% and 15%, respectively.

About KEYTRUDA^® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA^® (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) ≥1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) ≥10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

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.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

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

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). 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.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). 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.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

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 or 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.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. 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.

Contacts

Media Contacts:

Pamela Eisele

(267) 305-3558

Justine Moore

(908) 740-6449

Investor Contacts:

Peter Dannenbaum

(908) 740-1037

Courtney Ronaldo

(908) 740-6132

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