Pooled Analysis Continues to Show Merck’s KEYTRUDA® (pembrolizumab) in Combination with Chemotherapy Improved Overall Survival Versus Chemotherapy Alone as First-Line Treatment for Patients with Advanced NSCLC Whose Tumors Do Not Express PD-L1

Findings from Pooled Analysis of KEYNOTE-189, KEYNOTE-407 and KEYNOTE-021 (Cohort G) Presented at the IASLC 2019 World Conference on Lung Cancer

KENILWORTH, NJ, USA I September 10, 2019 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that first-line treatment with KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy demonstrated improvements in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) in a pooled analysis of a subgroup of patients with advanced nonsquamous and squamous non-small cell lung cancer (NSCLC) whose tumors do not express PD-L1 (tumor proportion score [TPS] <1%) from three randomized trials. Patients with nonsquamous NSCLC with EGFR or ALK genomic tumor aberrations were ineligible. Results – from KEYNOTE-189, KEYNOTE-407 and KEYNOTE-021 (Cohort G) – were consistent with those observed in the overall study populations across all three trials. Findings were featured in an oral presentation at the IASLC 2019 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain (Abstract #MA25.01).

“The goal of our robust lung cancer clinical development program has always been to extend survival for patients who are diagnosed with this deadly and aggressive disease,” said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. “In this pooled analysis of three randomized KEYNOTE studies in advanced non-small cell lung cancer, KEYTRUDA in combination with chemotherapy demonstrated an improvement in overall survival compared to chemotherapy alone among newly diagnosed patients whose tumors do not express PD-L1.”

Findings from the pooled subgroup analysis of 428 patients showed that KEYTRUDA in combination with chemotherapy reduced the risk of death by 44% (HR=0.56 [95% CI, 0.43-0.73]) compared to chemotherapy alone. The KEYTRUDA-chemotherapy combinations also reduced the risk of disease progression or death by 33% (HR=0.67 [95% CI, 0.54-0.84]) compared to chemotherapy alone. The ORR was 46.9% for patients treated with the KEYTRUDA-chemotherapy combinations versus 28.6% for those treated with chemotherapy alone. The safety profile of KEYTRUDA was consistent with what has been seen in previously reported studies among patients with advanced NSCLC.

“KEYTRUDA in combination with chemotherapy has become an important first-line therapy for appropriate patients with advanced non-small cell lung cancer based on the overall survival benefit observed in clinical trials,” said Dr. Hossein Borghaei, chief, Division of Thoracic Oncology, Fox Chase Cancer Center. “It is encouraging to see that in this subgroup analysis, first-line KEYTRUDA in combination with chemotherapy reduced the risk of death by 44% in patients with nonsquamous or squamous advanced non-small cell lung cancer whose tumors do not express PD-L1.”

Additional Data from Pooled Subgroup Analysis of KEYNOTE-189, KEYNOTE-407 and KEYNOTE-021 (Cohort G)

Data presented at WCLC are from a pooled subgroup of 428 previously untreated patients whose tumors do not express PD-L1 (TPS <1%) from the KEYNOTE-189 (nonsquamous NSCLC; n=190), KEYNOTE-407 (squamous NSCLC; n=194) and KEYNOTE-021 (nonsquamous NSCLC; n=44 [Cohort G]) trials. Patients were randomized to receive KEYTRUDA 200 mg every three weeks plus chemotherapy (n=243) or chemotherapy alone (n=185). Patients with nonsquamous NSCLC received pemetrexed (ALIMTA®) and platinum chemotherapy; patients with squamous NSCLC received carboplatin and either paclitaxel or nab-paclitaxel. Patients with nonsquamous NSCLC with EGFR or ALK genomic tumor aberrations were ineligible. Key efficacy outcome measures include OS, PFS and ORR.

With a median follow-up of 10.2 months, KEYTRUDA in combination with chemotherapy reduced the risk of death by 44% (HR=0.56 [95% CI, 0.43-0.73]) compared to chemotherapy alone. Estimated 12-month OS rates were 66% with the KEYTRUDA-chemotherapy combinations compared to 47% with chemotherapy alone; the 18-month OS rates were 52% and 29%, respectively. Median OS was 19.0 months (95% CI, 15.2-24.0) with the KEYTRUDA-chemotherapy combinations compared to 11.0 months (95% CI, 9.2-13.5) with chemotherapy alone.

The KEYTRUDA-chemotherapy combinations also reduced the risk of disease progression or death by 33% (HR=0.67 [95% CI, 0.54-0.84]) compared to chemotherapy alone. Estimated 12-month PFS rates were 29% with the KEYTRUDA-chemotherapy combinations compared to 17% with chemotherapy alone; the 18-month PFS rates were 22% and 9%, respectively. Median PFS was 6.5 months (95% CI, 6.2-8.5) with the KEYTRUDA-chemotherapy combinations compared to 5.4 months (95% CI, 4.7-6.2) with chemotherapy alone.

The ORR was 46.9% (n=114) for patients who received the KEYTRUDA-chemotherapy combinations and 28.6% (n=53) for those who received chemotherapy alone. Median DOR was 7.9 months (range, 1.1+ to 28.4+) with the KEYTRUDA-chemotherapy combinations and 6.7 months (range, 1.4+ to 30.1+) with chemotherapy alone. For patients receiving the KEYTRUDA- chemotherapy combinations, 42.4% experienced a response lasting 12 months or longer compared to 35.3% of those receiving chemotherapy alone.

Among patients who received KEYTRUDA in combination with chemotherapy, 68% (n=165) experienced a Grade 3-5 adverse event (AE) compared to 72% (n=131) of those who received chemotherapy alone. Grade 3-5 AEs that led to death occurred in 9% (n=23) of patients who received the KEYTRUDA-chemotherapy combinations and 6% (n=11) of those who received chemotherapy alone. Grade 3-5 immune-mediated AEs and infusion reactions occurred in 11% (n=27) of patients who received the KEYTRUDA-chemotherapy combinations compared to 3% (n=5) of those who received chemotherapy alone. Deaths resulting from immune-mediated AEs and infusion reactions occurred in 1% (n=2) of patients who received the KEYTRUDA-chemotherapy combinations compared to no deaths among patients who received chemotherapy alone.

The KEYNOTE-021 (Cohort G) and KEYNOTE-189 studies were conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (ALIMTA®).

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. Between 2008 and 2014, the five-year survival rate for patients diagnosed in the U.S. with advanced NSCLC was only 5%.

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.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,000 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.

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 one 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 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 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 the 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 [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 the 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.

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. 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).

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, the potential to bring new hope to people with cancer drives our purpose and supporting accessibility to our cancer medicines is our commitment. As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the largest development programs in the industry across more than 30 tumor types. We also continue to strengthen our portfolio through strategic acquisitions and are prioritizing the development of several promising oncology candidates with the potential to improve the treatment of advanced cancers. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

SOURCE: Merck

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