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FDA Approves Expanded Label for Merck’s Keytruda (pembrolizumab) in Patients with Metastatic Nonsquamous NSCLC with No EGFR or ALK Genomic Tumor Aberrations

KENILWORTH, N.J.--(BUSINESS WIRE) August 20, 2018 --Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved an expanded label for Keytruda, Merck’s anti-PD-1 therapy, in combination with pemetrexed (Alimta®) and platinum chemotherapy for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations, based on results of the KEYNOTE-189 trial. In the pivotal, Phase 3 KEYNOTE-189 trial of patients regardless of PD-L1 tumor expression status, Keytruda in combination with pemetrexed and platinum chemotherapy demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) (HR=0.49 [95% CI, 0.38-0.64]; p<0.00001), reducing the risk of death by half compared to chemotherapy alone. The study also showed a significant improvement in progression-free survival (PFS) compared to chemotherapy alone (HR=0.52 [95% CI, 0.43-0.64]; p<0.00001). Data from KEYNOTE-189 support that Keytruda is changing survival expectations for these patients.

“Keytruda is rapidly becoming a foundation for the treatment of appropriate patients with metastatic non-small cell lung cancer,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. “Today’s approval of the expanded label for Keytruda based on data from the KEYNOTE-189 trial is an important milestone, and reinforces our steadfast commitment to improving survival outcomes, and providing hope, for more patients with lung cancer.”

Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation (HSCT). Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate. Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman.

“Over the last few years, we’ve seen significant clinical advances and an incredible shift in the way we approach the treatment of people diagnosed with metastatic non-small cell lung cancer,” said Dr. Shirish Gadgeel, professor in thoracic oncology at the University of Michigan Rogel Cancer Center. “As a practicing physician, I welcome today’s news, as Keytruda in combination with pemetrexed and platinum chemotherapy significantly prolonged overall survival and progression-free survival in the KEYNOTE-189 trial, compared with chemotherapy alone.”

Keytruda in combination with pemetrexed and carboplatin was first approved in 2017 under the FDA’s accelerated approval process for the first-line treatment of patients with metastatic nonsquamous NSCLC, based on tumor response rates and progression-free survival data from the Phase 2 study (KEYNOTE-021, Cohort G1). In accordance with the accelerated approval process, continued approval was contingent upon verification and description of clinical benefit, which has now been demonstrated in KEYNOTE-189 and has resulted in the FDA converting the accelerated approval to full (regular) approval. Keytruda is the first anti-PD-1 approved in the first-line setting as both combination and monotherapy in certain patients with metastatic NSCLC.

Data Supporting the Approval

The approval was based on data from KEYNOTE-189, a Phase 3, randomized, multicenter, double-blind, active-controlled trial in systemic-therapy naïve patients with metastatic NSCLC, regardless of PD-L1 tumor expression status and with no EGFR or ALK genomic tumor aberrations. Patients with autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required immunosuppression; or patients who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were ineligible. Patients were randomized to receive Keytruda 200 mg, cisplatin or carboplatin, and pemetrexed intravenously Q3W for 4 cycles followed by Keytruda 200 mg for up to 24 months and pemetrexed Q3W (n=410); or cisplatin or carboplatin and pemetrexed intravenously Q3W for 4 cycles followed by pemetrexed Q3W (n=206). Treatment continued until progression of disease or unacceptable toxicity. Primary efficacy outcome measures were OS and PFS assessed by blinded independent central review (BICR) per RECIST v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ). Secondary efficacy outcome measures were overall response rate (ORR) and duration of response (DOR). Patients receiving chemotherapy and pemetrexed who experienced disease progression could cross over to receive Keytruda as monotherapy. The KEYNOTE-189 study was conducted in collaboration with Eli Lilly and Company, the makers of pemetrexed (Alimta®).

Efficacy Results in KEYNOTE-189

Endpoint Keytruda

Pemetrexed

Platinum Chemotherapy

n=410

Placebo

Pemetrexed

Platinum Chemotherapy

n=206

OS
Number (%) of patients with event 127 (31%) 108 (52%)
Median in months (95% CI) NR

(NR, NR)

11.3

(8.7, 15.1)

Hazard ratio* (95% CI) 0.49 (0.38, 0.64)
p-Value <0.00001
PFS
Number of patients with event (%) 244 (60%) 166 (81%)
Median in months (95% CI) 8.8 (7.6, 9.2) 4.9 (4.7, 5.5)
Hazard ratio* (95% CI) 0.52 (0.43, 0.64)
p-Value <0.00001
ORR
Overall response rate(95% CI) 48% (43, 53) 19% (14, 25)
Complete response 0.5% 0.5%
Partial response 47% 18%
p-Value§ <0.0001
Duration of Response
Median in months (range) 11.2 (1.1+, 18.0+) 7.8 (2.1+, 16.4+)
* Based on the stratified Cox proportional hazard model

Based on stratified log-rank test

Response: Best objective response as confirmed complete response or partial response

§ Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status

NR = not reached

In KEYNOTE-189, safety was evaluated in 405 patients who received Keytruda in combination with pemetrexed and platinum chemotherapy and 202 patients who received placebo, pemetrexed, and platinum chemotherapy. Keytruda was discontinued for adverse reactions in 20 percent of patients. The most common adverse reactions resulting in permanent discontinuation of Keytruda were pneumonitis (3%) and acute kidney injury (2%). Adverse reactions leading to the interruption of Keytruda occurred in 53 percent of patients; the most common adverse reactions or laboratory abnormalities leading to interruption of Keytruda (≥5%) were neutropenia (13%), asthenia/fatigue (7%), anemia (7%), and thrombocytopenia (5%). Adverse reactions of any grade occurring in at least 20 percent of patients receiving Keytruda in combination with pemetrexed and platinum chemotherapy were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

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 750 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.

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 the Merck Access Program for Keytruda

At Merck, we are committed to supporting accessibility to our cancer medicines. Merck provides multiple programs to help ensure that appropriate patients who are prescribed Keytruda have access to our anti-PD-1 therapy. The Merck Access Program provides reimbursement support for patients receiving Keytruda, including information to help with out-of-pocket costs and co-pay assistance for eligible patients. Merck also offers free product through our patient assistance program to eligible patients, primarily the uninsured, who, without our assistance, could not afford their medicine. More information is available by calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com.

About Merck’s Patient Support Program for Keytruda

Merck is committed to helping provide patients and their caregivers support throughout their treatment with Keytruda. The KEY+YOU Patient Support Program provides a range of resources and services. For further information and to sign up, patients and physicians may call 85-KEYTRUDA (855-398-7832) or visit www.keytruda.com.

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.

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 2017 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).

Source: Merck

Posted: August 2018

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