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FDA Approves Keytruda (pembrolizumab) in Combination With Inlyta (axitinib) as First-Line Treatment for Patients With Advanced Renal Cell Carcinoma (RCC)

KENILWORTH, N.J.--(BUSINESS WIRE)--April 22, 2019 --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 Keytruda, Merck’s anti-PD-1 therapy, in combination with Inlyta (axitinib), a tyrosine kinase inhibitor, for the first-line treatment of patients with advanced renal cell carcinoma (RCC). The approval is based on findings from the pivotal Phase 3 KEYNOTE-426 trial, which demonstrated significant improvements in overall survival (OS), progression-free survival (PFS) and objective response rate (ORR) for Keytruda in combination with axitinib (Keytruda-axitinib combination) compared to sunitinib. Consistent results were observed across pre-specified subgroups, IMDC risk categories and PD-L1 tumor expression status. For the main efficacy outcome measures of OS and PFS, the Keytruda-axitinib combination reduced the risk of death by 47% compared to sunitinib (HR=0.53 [95% CI, 0.38-0.74]; p<0.0001); for PFS, the Keytruda-axitinib combination showed a reduction in the risk of progression of disease or death of 31% compared to sunitinib (HR=0.69 [95% CI, 0.57-0.84]; p=0.0001). The ORR, an additional efficacy outcome measure, was 59% for patients who received the Keytruda-axitinib combination (95% CI, 54-64) and 36% for those who received sunitinib (95% CI, 31-40) (p<0.0001). This is the first indication for Keytruda in advanced RCC, the most common type of kidney cancer, and the first anti-PD-1 therapy FDA-approved as part of a combination regimen that significantly improved OS, PFS, and ORR versus sunitinib in patients with advanced RCC.

“This represents a new treatment option for patients with advanced renal cell carcinoma, who will now have access to Keytruda as part of a first-line combination regimen,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “Today’s approval reflects Merck’s commitment to patients with cancer and further supports the use of Keytruda to help improve survival outcomes for patients with advanced renal cell carcinoma.”

Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, 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. For more information, see “Selected Important Safety Information” below.

“Given the aggressive nature of the disease, many patients with advanced renal cell carcinoma need additional treatment options that can help improve survival outcomes,” said Dr. Brian Rini, medical oncologist at Cleveland Clinic Cancer Center and professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. “Pembrolizumab in combination with axitinib offers an important new therapeutic option for physicians to consider when approaching initial treatment for patients newly diagnosed with advanced renal cell carcinoma.” Dr. Rini reports consulting and research funding from Merck.

About KEYNOTE-426

The approval was based on data from the pre-specified interim analysis of the Phase 3 KEYNOTE-426 trial, a randomized, multi-center, open-label trial conducted in 861 patients who had not received systemic therapy for advanced RCC. Patients were enrolled regardless of PD-L1 tumor expression status. Randomization was stratified by International Metastatic RCC Database Consortium (IMDC) risk categories (favorable versus intermediate versus poor) and geographic region (North America versus Western Europe versus “Rest of the World”). Patients with active autoimmune disease requiring systemic immunosuppression within the last two years were ineligible.

Patients were randomized (1:1) to one of the following treatment arms:

  • Keytruda 200 mg intravenously every three weeks up to 24 months in combination with axitinib 5 mg orally, twice daily (n=432).
  • Sunitinib 50 mg orally, once daily for four weeks and then off treatment for two weeks (n=429).

Among the 861 patients, the study population characteristics were: median age of 62 years (range, 26 to 90); 38% age 65 or older; 73% male; 79% White and 16% Asian; 19% and 80% of patients had a baseline Karnofsky Performance Status (KPS) of 70 to 80 and 90 to 100, respectively; and patient distribution by IMDC risk categories was 31% favorable, 56% intermediate, and 13% poor.

Treatment with the Keytruda-axitinib combination continued until RECIST v1.1 (modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ)-defined progression of disease or unacceptable toxicity. The main efficacy outcome measures were OS and PFS as assessed by BICR according to modified RECIST v1.1. Additional efficacy outcome measures included ORR, as assessed by BICR.

The trial demonstrated statistically significant improvements in OS, PFS, and ORR in patients randomized to receive the Keytruda-axitinib combination compared to sunitinib.

With a median follow-up time of 12.8 months (range, 0.1 to 22 months), OS was significantly improved in patients who received the KEYTRUDA-axitinib combination compared to sunitinib (HR=0.53 [95% CI, 0.38-0.74]; p<0.0001). Estimated 12-month OS rates were 90% (95% CI, 86-92) with the Keytruda-axitinib combination versus 78% (95% CI, 74-82) with sunitinib. Median OS was not reached with either treatment regimen. Progression-free survival was also significantly improved with the Keytruda-axitinib combination compared to sunitinib (HR=0.69 [95% CI, 0.57-0.84]; p=0.0001). Median PFS was 15.1 months (95% CI, 12.6-17.7) in patients receiving the Keytruda-axitinib combination versus 11.1 months (95% CI, 8.7-12.5) with sunitinib. In the study, the ORR was 59% for patients who received the Keytruda-axitinib combination (95% CI, 54-64) and 36% for those who received sunitinib (95% CI, 31-40) (p<0.0001), with a complete response rate of 6% and 2% and a partial response rate of 53% and 34%, for patients receiving the Keytruda-axitinib combination versus sunitinib, respectively.

In KEYNOTE-426, the safety of Keytruda in combination with axitinib was investigated in patients with previously untreated, advanced RCC. The median duration of exposure to the combination therapy of Keytruda and axitinib was 10.4 months (range, 1 day to 21.2 months). Fatal adverse reactions occurred in 3.3% of patients receiving Keytruda in combination with axitinib. Serious adverse reactions occurred in 40% of patients receiving Keytruda in combination with axitinib. Serious adverse reactions in ≥1% of patients receiving Keytruda in combination with axitinib included hepatotoxicity (7%), diarrhea (4.2%), acute kidney injury (2.3%), dehydration (1%), and pneumonitis (1%). Permanent discontinuation due to an adverse reaction of either Keytruda or axitinib occurred in 31% of patients; 13% Keytruda only, 13% axitinib only, and 8% both drugs. The most common adverse reaction (>1%) resulting in permanent discontinuation of Keytruda, axitinib or the combination was hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney injury (1.6%), and cerebrovascular accident (1.2%). The most common adverse reactions (≥20%) in patients receiving in patients receiving Keytruda and axitinib were diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased appetite (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal inflammation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

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 950 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. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

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 2018 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: April 2019

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