Clinical Trials

Date: 2014-09-29

Type of information: Presentation of results at a congress

phase: 1b

Announcement: presentation of results at the 2014 Congress of the European Society for Medical Oncology (ESMO)

Company: Merck&Co (USA - NJ)

Product: Keytruda® (pembrolizumab)

Action mechanism:

• monoclonal antibody/immune checkpoint inhibitor. Keytruda® (pembrolizumab - MK-3475) is an investigational, highly selective monoclonal anti-PD-1 antibody 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 three clinical trials for advanced melanoma including a Phase III trial of MK-3475 versus ipilimumab in ipilimumab-naïve advanced melanoma patients (PN 006). Enrollment is complete in the advanced melanoma cohorts in the company’s Phase IB trial (PN 001) and the Phase II trial (PN 002) comparing two doses of MK-3475 versus chemotherapy in patients with advanced melanoma who have progressed after prior therapy. Pembrolizumab is being evaluated across more than 30 types of cancers, as monotherapy and in combination. It is anticipated that by the end of 2014, the pembrolizumab development program will grow to more than 24 clinical trials, enrolling an estimated 6,000 patients at nearly 300 clinical trial sites worldwide.

Disease: PD-L1 positive, advanced urothelial cancer (also known as bladder cancer)

Therapeutic area: Cancer - Oncology

Country: Belgium, Israel, Japan, Republic of Korea, Taiwan, USA

Trial details:

• KEYNOTE-012 is an ongoing multi-center, non-randomized Phase 1b trial evaluating the safety, tolerability, and anti-tumor activity of Keytruda® 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-tumor activity (as measured by RECIST v1.1) in PD-L1 positive tumors; secondary endpoints include progression-free survival (PFS), overall survival (OS) and duration of response. (NCT01848834)

Latest news:

• • On September 29, 2014, Merck & Co announced the first presentation of data on the investigational use of Keytruda® in PD-L1 positive, advanced urothelial cancer (also known as bladder cancer). The early findings presented showed a confirmed overall response rate of 24 percent with Keytruda® as monotherapy, as measured by RECIST v1.1, central review (n= 7/29: 95% CI, 10.3-43.5) including a complete response rate of 10 percent (3/29). At the time of analysis, response durations ranged from 16+ to 40+ weeks with six of the seven responders continuing on therapy. In the ongoing study, 64 percent (61/95) of patients screened had tumors that were determined to be positive for PD-L1 expression. These data, from a cohort of the ongoing Phase 1b KEYNOTE-012 study, were presented, as part of a late-breaking oral session, by Dr. Elizabeth R. Plimack, Fox Chase Cancer Center, Philadelphia, at the European Society for Medical Oncology (ESMO) 2014 Congress in Madrid, Spain (ABSTRACT #LBA23).
• Data from a cohort of the ongoing Phase 1b KEYNOTE-012 study evaluated Keytruda® monotherapy at 10 mg/kg every two weeks in patients with advanced bladder cancer whose tumors were determined to be positive for PD-L1 expression (n=29). As measured by Merck’s proprietary immunohistochemistry (IHC) clinical trial assay, tumors were classified as PD-L1 positive based on greater than or equal to one percent of tumor cells demonstrating expression of the PD-L1 marker, or any positive staining with the same reagent in tumor stroma. The majority of patients had received one or more prior lines of therapy.
• Antitumor activity by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1*

						Patients Evaluable for Response (n=29)
						n				Percentage				95% CI
Overall Response Rate (ORR)						7				24.1				10.3 – 43.5
Best overall response
Complete response						3				10.3				2.2 – 27.4
Partial response						4				13.8				3.9 – 31.7
Stable disease						4				13.8				3.9 – 31.7
Progressive disease						14				48.3				29.4 – 67.5
No assessment						4				13.8				3.9 – 31.7

• *Analysis cut-off date: August 6, 2014
• At six months, 58 percent of patients were alive and median overall survival was 9.3 months (95% CI, 3.6-NR). Additionally, tumor shrinkage was achieved in 64 percent of evaluable patients with one post-baseline treatment scan. Analysis of the relationship between PD-L1 expression and clinical outcomes is ongoing. Adverse events were consistent with previously reported safety data for Keytruda. The most common investigator-assessed, treatment-related adverse events (occurring in greater than or equal to two patients) included fatigue (18%), peripheral edema (12%), and nausea (9%). Grade 3-5 investigator-assessed, treatment-related adverse events occurred in a total of four patients. One infusion-related reaction was observed and one patient discontinued Keytruda due to a treatment-related adverse reaction. There were no treatment-related deaths.

Is general: Yes