MSD Announces First Presentation of Data on the Investigational Use of Pembrolizumab in Patients with Advanced Gastric Cancer at ESMO 2014

Pembrolizumab monotherapy achieved 31 percent overall response rate in patients with PD-L1 positive, advanced gastric cancer

Phase 2 study to be initiated in first quarter of 2015 (KEYNOTE-059)

Sunday, September 28, 2014 3:15 am EDT
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WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--MSD, known as Merck in the United States and Canada, today announced the first presentation of data on the investigational use of pembrolizumab – the company's anti-PD-1 therapy – in PD-L1 positive, advanced gastric cancer. The early findings presented showed an overall response rate (confirmed and unconfirmed) of 31 percent with pembrolizumab as monotherapy, as measured by investigator assessed, RECIST v1.1 (n= 12/39: 95% CI, 17-47). Similar overall response rates were observed in Asian patients (a population with a high incidence of gastric cancer) and non-Asian patients. At the time of analysis, response durations ranged from 8+ to 20+ weeks with 11 of 12 responders continuing on therapy.

These data, from a cohort of the ongoing Phase 1b KEYNOTE-012 study, were presented today, as part of a late-breaking abstract oral session, by Dr. Kei Muro, Aichi Cancer Center Hospital, Nagoya, Japan, at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain (ABSTRACT #LBA15). Data investigating the use of pembrolizumab monotherapy in five tumour types will be presented at ESMO 2014.

"MSD is advancing the development of pembrolizumab across different tumour types and lines of therapy," said Dr. Alise Reicin, vice president, oncology, Merck Research Laboratories. "We are encouraged by the signals of anti-tumour activity in advanced gastric cancer, and are eager to move ahead with the Phase 2 study to better understand the potential of pembrolizumab in advanced gastric cancer."

Early findings for investigational use of pembrolizumab in advanced gastric cancer

Data from a cohort of the ongoing Phase 1b KEYNOTE-012 study evaluated pembrolizumab monotherapy at 10 mg/kg every two weeks in patients with advanced gastric cancer whose tumours were determined to be positive for PD-L1 expression (n=39). As measured by MSD's proprietary immunohistochemistry (IHC) clinical trial assay, tumours were classified as PD-L1 positive based on greater than or equal to one percent of tumour cells demonstrating expression of the PD-L1 marker, or any positive staining with the same reagent in tumour stroma. Enrollment was designed to include an equal number of Asian and non-Asian patients. The majority of patients had received two or more prior lines of therapy.


Antitumour activity by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1*
   
Total
n = 39
 
Non-Asian
n = 20
 
Asian
n = 19
Overall Response Rate (ORR), % (95% CI)   31 (17-47)   30 (12-54)   31 (12-56)
Disease Control Rate (DCR), % (95% CI)   43 (28-60)   35 (15-59)   52 (29-75)
Best overall response, n (%)
Complete response
  0   0   0
Partial response
  12 (31)   6 (30)   6 (32)
Stable disease
  5 (13)   1 (5)   4 (21)
Progressive disease
  21 (54)   12 (60)   9 (47)
No assessment
  1 (2)   1 (5)   0
       
*Analysis cut-off date: 6 August 2014

Using a prototype assay for PD-L1 assessment, there was evidence of a preliminary relationship between PD-L1 expression and ORR (P = 0.071)

In the study, tumour shrinkage was demonstrated in 41 percent of evaluable patients who had measurable disease with one post baseline scan, per RECIST v1.1 criteria.

Adverse events were consistent with previously reported safety data for pembrolizumab. The most common investigator-assessed, treatment-related adverse events (occurring in greater than five percent) included hypothyroidism (12.8%) and fatigue (12.8%). Grade 3-5 investigator-assessed, treatment-related adverse events occurred in a total of three patients, with one patient each in peripheral sensory neuropathy (Grade 3), hypoxia (Grade 5) and pneumonitis (Grade 4). No infusion-related reactions were observed and no patients discontinued pembrolizumab due to a treatment-related adverse reaction. One treatment-related death due to hypoxia, as assessed by the investigator, was reported.

About the KEYNOTE-012 study

KEYNOTE-012 is an ongoing multi-center, non-randomized Phase 1b trial evaluating the safety, tolerability, and anti-tumour activity of pembrolizumab monotherapy in patients with advanced triple negative breast cancer (TNBC), advanced head and neck cancer, advanced urothelial (bladder) cancer, or advanced gastric cancer. The primary endpoints of the study include overall safety, tolerability, and anti-tumour activity (as measured by RECIST v1.1) in PD-L1 positive tumours; secondary endpoints include progression-free survival (PFS), overall survival (OS) and duration of response.

Presentation of additional findings investigating the use of pembrolizumab in advanced non-small cell lung cancer (NSCLC)

Also presented today, were updated findings in patients with treatment-naïve or previously treated advanced non-small cell lung cancer (NSCLC) across cohorts from the ongoing Phase 1b KEYNOTE-001 study (Abstract #LBA43). Data presented in a late-breaking oral session showed anti-tumour activity [overall response rate (ORR)] with pembrolizumab in both treatment-naïve and previously treated patients with advanced NSCLC (n=236) of 26 and 20 percent, respectively, across all doses and schedules assessed as measured by independent central review, RECIST v1.1. Analysis by dose (2 mg/kg every three weeks, 10 mg/kg every three weeks, and 10 mg/kg every two weeks) showed comparable ORR across dosing schedules (33 percent, 21 percent, and 21 percent, respectively).

Notes to the Editors

About pembrolizumab

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, pembrolizumab releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumour immune response.

About gastric cancer

Gastric cancer, also called stomach cancer, is a type of cancer that begins in the stomach.1 Most gastric cancers are adenocarcinomas, which develop from the cells of the innermost lining (mucosa) of the stomach.1 Among others, risk factors for gastric cancer include gender, age, ethnicity, geography and bacterial infection with Helicobacter pylori.1 More than 70 percent of gastric cancer cases occur in developing countries, with half of all cases occurring in Eastern Asia (predominately China).2 Worldwide, gastric cancer is the fifth most common type of cancer and the third leading cause of cancer death.2

Our focus on cancer

Our goal is to translate breakthrough science into biomedical innovations to help people with cancer worldwide. For MSD Oncology, helping people fight cancer is our passion, supporting accessibility to our cancer medicines is our commitment, and pursuing research in immuno-oncology is our focus to potentially bring new hope to people with cancer. For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About MSD

Today's MSD is a global healthcare leader working to help the world be well. MSD is known as Merck in the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care 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 healthcare through far-reaching policies, programs and partnerships.

Forward-Looking Statement

This news release includes "forward-looking statements" within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of MSD'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 healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; MSD'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 MSD's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

MSD 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 Merck's 2013 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).

1 American Cancer Society. Stomach Cancer. http://www.cancer.org/acs/groups/cid/documents/webcontent/003141-pdf.pdf. Accesses September 17, 2014.

2 World Health Organization. Globocan 2012 Stomach Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/old/FactSheets/cancers/stomach-new.asp. Accessed September 17, 2014.

 

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