Merck Announces Presentation of Interim Data from Phase 1B Study of MK-3475, Investigational anti-PD-1 Immunotherapy, in Previously-Treated Patients with Non-Small Cell Lung Cancer (NSCLC) at 15th World Conference on Lung Ca

Tue Oct 29, 2013 1:15am EDT

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Merck Announces Presentation of Interim Data from Phase 1B Study of MK-3475, Investigational anti-PD-1 Immunotherapy, in Previously-Treated Patients with Non-Small Cell Lung Cancer (NSCLC) at 15th World Conference on Lung Cancer

Phase II/III Trial of MK-3475 in Patients with NSCLC Currently Enrolling

Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of interim data from a Phase 1B trial (PN001) evaluating MK-3475, an investigational anti-PD-1 immunotherapy, in patients with previously-treated non-small cell lung cancer (NSCLC). The data were presented today by Dr. Edward Garon, Director of Thoracic Oncology, Jonsson Comprehensive Cancer Center, University of California, Los Angeles, at the 15th World Conference on Lung Cancer in Sydney, Australia (Abstract # MO18.02).

Detailed interim data were presented for response rates and safety from a cohort of 38 previously-treated NSCLC patients who received MK-3475 10mg/kg every three weeks as well as initial findings from an analysis of the relationship between response rates and PD-L1 expression.

“We are encouraged by these initial responses in NSCLC patients,” said Dr. Eric H. Rubin, vice president, Oncology, Merck Research Laboratories. “Based on these preliminary data and other research, we believe that PD-L1 expression has the potential to be a useful predictor of response to MK-3475 in certain cancers. We look forward to further data from this and other studies to help us to understand the potential role of MK-3475 in lung cancer, and of PD-L1 as a biomarker.”

Based on data from this Phase IB study, Merck initiated a Phase II/III trial comparing two doses of MK-3475, 10mg/kg every three weeks and 2mg/kg every three weeks (10mg/kg Q3W and 2mg/kg Q3W), versus docetaxel in previously-treated patients with NSCLC who have received at least one prior treatment regimen (see clinicaltrials.gov). Merck plans to present data from ongoing studies evaluating 10mg/kgQ2W and 10mg/kgQ3W dosing regimens for MK-3475 in patients with NSCLC in 2014.

Interim results presented at International Association for Study of Lung Cancer 2013

Tumor responses were assessed by investigator-assessed, immune-related response (irRC) criteria as well as independent, central, blinded radiographic review per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) criteria.

In the 38-patient cohort, the objective response rate in patients receiving MK-3475 was 24 percent based on irRC, and 21 percent based on RECIST (n=33). The median overall survival at time of analysis was 51 weeks with seven of the nine responders, determined by irRC, continuing on treatment. The median response duration has not been reached at the time of this analysis. Detailed results as presented are shown below:

Interim efficacy data for MK-3475 (10mg/kg Q3W) in previously treated patients with advanced NSCLC

 
Subgroup   irRC Investigator Assessment   RECIST 1.1 Independent Review  

Median
OS
Weeks
(95% CI)

 

  N   1ORR n (%)

[95% CI]

  Median PFS

Weeks

(95% CI)

  N   1*ORR n (%)

[95% CI]

  Median PFS

Weeks

(95% CI)

 
Non squamous   31   7 (23)

[10,41]

  9.1

(8.3, 17.0)

  26   4 (16)

[4,35]

  10.3

(7.6,17)

 

35
(14,NR)

Squamous   6   2 (33)

[4,78]

  23.5

(2.7,NR)

  6   2 (33)

[4,78]

  15.2

(1.4,NR)

  NR

(2.7,NR)

Total   38   9 (24)

[11,40]

  9.1

(8.3,17.4)

  33   7 (21)

[9,39]

  9.7

(7.6,17)

  51

(14,NR)

NR=Not Reached; OS= Overall Survival; PFS= Progression-Free Survival
1Objective response rate (ORR) = confirmed complete (CR) and partial response (PR)
*Response rate per RECIST v1.1 is based on those patients who had ≥1 measurable lesion at baseline per central review. All responses were confirmed except for 2. One patient withdrew consent for treatment, unrelated to toxicity, after the first imaging assessment, and 1 patient had a confirmatory scan of PR at day 27.

The most commonly reported drug-related adverse events in the study, (all grades), were: rash (21%), pruritus (18%), fatigue (16%), diarrhea (13%) and arthralgia (11%). The majority of adverse events were low grade (grade 1-2) there was one incident of grade 3 pulmonary edema.

An analysis of the relationship between PD-L1 expression status and response rates in this NSCLC patient cohort was also presented. Tumor samples were analyzed and classified as expressing either zero/low or high levels of PD-L1. High levels of expression according to the assay criteria, were associated with response rates of 67 percent (6/9) [95% CI; range 30, 93] per irRC and 57 percent (4/7) [95% CI; range 18, 90] per RECIST. In comparison, tumor samples expressing zero/low levels of PD-L1, according to assay criteria, were associated with response rates of 4 percent (1/24) [95% CI; range 0, 21] per irRC and 9 percent (2/22) per RECIST [95% CI; range 1, 29]. Data from more patients are needed to better understand the relationship between PD-L1 expression and response to MK-3475.

About MK-3475

Many tumors are able to evade the immune system through a mechanism that exploits the PD-1 inhibitory checkpoint protein. MK-3475 is an investigational, highly selective anti-PD-1 immunotherapy designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein. By blocking PD-1, MK-3475 enables activation of the immune system’s T-cells that target cancer by essentially releasing a brake on the immune system.

MK-3475 is currently being studied in eight clinical trials estimated to enroll over 3,000 patients across a broad range of cancer types including: bladder, colorectal, gastric, head and neck, melanoma, non-small cell lung, triple negative breast and hematological malignancies. Additional trials both as monotherapy and in combination with other cancer therapies are planned. The expansion of the MK-3475 clinical development program is based on preliminary clinical evidence from Merck’s large foundational Phase IB trial (PN 001) evaluating MK-3475 monotherapy in more than 1,000 patients with diverse late-stage cancers (metastatic carcinoma).

About Lung Cancer

Lung cancer is the leading cause of cancer death worldwide in both men and women, with an estimated 1.4 million deaths worldwide each year, according to the American Cancer Society. NSCLC is the most common type of lung cancer representing about 85 percent of all lung cancer diagnoses.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside 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. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Merck 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 Merck’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; Merck’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 Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck 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 2012 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).

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