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New Combination Data for Merck’s KEYTRUDA® (pembrolizumab) Demonstrated Clinical Benefit in Stage III Non-Small Cell Lung Cancer (NSCLC) and Reinforce Long-Term Survival in Metastatic NSCLC

First Combination Data in Stage III NSCLC from KEYNOTE-799 Showed KEYTRUDA Plus Concurrent Chemoradiation Achieved Objective Response Rate of 67.0% and 56.6% in Two Cohorts

In the Final Analysis of KEYNOTE-189, KEYTRUDA in Combination with Chemotherapy Reduced the Risk of Death by 44% Versus Chemotherapy and at Two Years, Demonstrated a Sustained, Long-Term Survival Benefit in Metastatic NSCLC

KENILWORTH, N.J.–(BUSINESS WIRE)–$MRK #MRK–Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced positive results from two studies from the company’s leading lung cancer research program. Initial results from the Phase 2 KEYNOTE-799 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, plus concurrent chemoradiation therapy (CCRT) demonstrated an objective response rate (ORR) of 67.0% in Cohort A (squamous and nonsquamous non-small cell lung cancer [NSCLC] patients who received paclitaxel plus carboplatin) and 56.6% in Cohort B (nonsquamous NSCLC patients who received cisplatin plus pemetrexed) in untreated patients with unresectable, locally advanced stage III NSCLC. Additionally, new and updated data from the final analysis of the pivotal Phase 3 KEYNOTE-189 trial showed that 45.7% of patients with metastatic nonsquamous NSCLC treated with KEYTRUDA in combination with chemotherapy were alive at two years versus 27.3% of patients treated with chemotherapy alone.

KEYTRUDA has become a standard of care in metastatic non-small cell lung cancer based on the strength of clinical data showing a survival benefit as monotherapy or in combination with chemotherapy,” said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “New data from KEYNOTE-799 demonstrate the potential of KEYTRUDA plus concurrent chemoradiation therapy in earlier stages of lung cancer, while the long-term survival data from KEYNOTE-189 add to the strong body of evidence supporting the use of KEYTRUDA in combination with chemotherapy for appropriate patients with metastatic non-small cell lung cancer.”

Approximately 20-30% of patients with unresectable stage III non-small cell lung cancer have disease progression after initially receiving chemoradiation,” said Salma K. Jabbour, radiation oncologist, professor, vice chair of clinical research, Rutgers Cancer Institute of New Jersey. “The encouraging results from KEYNOTE-799 demonstrate that combining KEYTRUDA with concurrent chemoradiation therapy has the potential to address a significant unmet medical need.”

Merck is a leader in lung cancer, with an extensive clinical development program evaluating KEYTRUDA, in combination or as monotherapy, for the treatment of lung cancer across all stages of disease and lines of therapy in over 200 trials with more than 10,000 patients. In addition to KEYNOTE-799, Merck has initiated the Phase 3 KEYLYNK-012 study (ClinicalTrials.gov, NCT04380636), which will evaluate KEYTRUDA plus CCRT followed by one year of KEYTRUDA alone or in combination with LYNPARZA® (olaparib) post-CCRT in patients with unresectable, locally advanced stage III NSCLC. KEYLYNK-012 is one of three new pivotal Phase 3 trials evaluating KEYTRUDA in combination with LYNPARZA for NSCLC. Additional studies include KEYLYNK-006 (nonsquamous patients; ClinicalTrials.gov, NCT03976323) and KEYLYNK-008 (squamous patients; ClinicalTrials.gov, NCT03976362), evaluating KEYTRUDA and maintenance LYNPARZA for the first-line treatment of metastatic NSCLC.

Results from KEYNOTE-799 (Abstract #9008) and KEYNOTE-189 (Abstract #9582) are being presented during the virtual scientific program of the 2020 American Society of Clinical Oncology (ASCO) Annual Meeting. 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. Follow Merck on Twitter via @Merck and keep up to date with ASCO news and updates by using the hashtag #ASCO20.

First Presentation of Data from KEYNOTE-799 in Stage III NSCLC (Abstract #9008)

KEYNOTE-799 (ClinicalTrials.gov, NCT03631784) is a Phase 2, non-randomized, open-label study of 216 untreated patients with unresectable, locally advanced stage IIIA–C NSCLC designed to evaluate the efficacy of KEYTRUDA plus CCRT. All patients received KEYTRUDA, standard thoracic radiotherapy and investigator’s choice of two chemotherapy regimens. Cohort A included patients across NSCLC histologies who received paclitaxel plus carboplatin and Cohort B included only nonsquamous NSCLC patients who received cisplatin plus pemetrexed. Primary endpoints are ORR and rate of Grade ≥3 pneumonitis. Secondary endpoints include progression-free survival (PFS), overall survival (OS) and safety.

In all patients from Cohort A (n=112) and Cohort B (n=53) with a minimum of 15 weeks of follow-up, KEYTRUDA plus CCRT showed an ORR of 67.0% (90% CI, 58.9-74.3) and 56.6% (90% CI, 44.4-68.2) for Cohort A (2.7% complete response [CR]) and Cohort B (3.8% CR), respectively. The median duration of response (DOR) was not reached in either Cohort A (range, 1.6+ to 10.5+) or Cohort B (range, 1.7+ to 10.5+) as of data cutoff. Additionally, 91.1% and 100% of patients in Cohort A and B, respectively, had a response lasting six months or longer. In Cohort A, the six-month PFS rate was 81.4% and the six-month OS rate was 87.2%. In Cohort B, the six-month PFS rate was 85.2% and the six-month OS rate was 94.8%.

The incidence of adverse events (AEs) among patients who received KEYTRUDA plus CCRT was consistent with the established toxicity profiles of CCRT for stage III NSCLC and KEYTRUDA monotherapy. All-cause Grade ≥3 pneumonitis occurred in 8.0% (n=9) of patients in Cohort A and 5.5% (n=4) of patients in Cohort B; four deaths (Grade 5 pneumonitis) occurred in Cohort A. Observed rates of Grade ≥3 pneumonitis were within the expected range for immunotherapy combined with CCRT. The incidence of treatment-related Grades 3-5 AEs was 64.3% (n=72) in Cohort A and 41.1% (n=30) in Cohort B. Treatment-related AEs leading to discontinuation of any treatment component occurred in 28.6% (n=32) of patients in Cohort A and 12.3% (n=9) in Cohort B.

New Two-Year Survival Data from KEYNOTE-189 in Metastatic NSCLC (Abstract #9582)

New and updated data from the protocol-specified final analysis of KEYNOTE-189 (ClinicalTrials.gov, NCT02578680) continue to show that KEYTRUDA in combination with chemotherapy maintained a sustained, long-term survival benefit over chemotherapy alone after 31.0 months of median follow-up. The pivotal Phase 3 KEYNOTE-189 trial evaluated KEYTRUDA in combination with pemetrexed (ALIMTA®) and platinum (cisplatin or carboplatin) chemotherapy for the first-line treatment of metastatic nonsquamous NSCLC compared with pemetrexed plus platinum alone in patients with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA in combination with chemotherapy reduced the risk of death by 44% (HR=0.56 [95% CI, 0.46-0.69]) compared with chemotherapy alone, with a median OS of 22.0 versus 10.6 months. The two-year OS rate was 45.7% for KEYTRUDA in combination with chemotherapy versus 27.3% with chemotherapy alone. KEYTRUDA in combination with chemotherapy also reduced the risk of disease progression or death by half (HR=0.49 [95% CI, 0.41-0.59]) compared with chemotherapy alone, with a median PFS of 9.0 versus 4.9 months. The two-year PFS rate was 22.0% for KEYTRUDA in combination with chemotherapy versus 3.4% for chemotherapy alone. The ORR was 48.3% for KEYTRUDA in combination with chemotherapy versus 19.9% for chemotherapy alone.

Among the 56 patients who completed two years of treatment with KEYTRUDA, the ORR was 85.7%. Median OS was not reached.

The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with metastatic NSCLC. Grades 3-5 AEs occurred in 72.1% of patients who received KEYTRUDA in combination with chemotherapy and 66.8% of patients who received chemotherapy alone. KEYNOTE-189 was conducted in collaboration with Eli Lilly and Company, the makers of ALIMTA® (pemetrexed).

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 Lung Cancer

Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. Each year, more people die of lung cancer than die of colon and breast cancers combined. The two main types of lung cancer are non-small cell and small cell. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for about 85% of all cases. Small cell lung cancer (SCLC) accounts for about 10 to 15% of all lung cancers. The five-year survival rate for patients diagnosed in the U.S. with NSCLC and SCLC is estimated to be 5% and 6%, 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® 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® (pembrolizumab)

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.

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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