Early Results Show Promise for Anti-PD-1 Antibody MK-3475 in NSCLC

The investigational immunotherapy MK-3475 has demonstrated an objective response rate (ORR) of up to 24% in patients with previously treated non-small cell lung cancer (NSCLC), according to interim results from a phase Ib expansion study. A new nonproprietary generic name for MK-3475 (previously known as lambrolizumab) is currently under review by the United States Adopted Names Council.

MK-3475, a monoclonal IgG4 antibody, is in a class of agents that target PD-1, an inhibitory T-cell co-receptor. It is thought that interactions between PD-1 and the ligands PD-L1 or PD-L2 can lead to antitumor immune suppression. Additionally, preclinical evidence has supported this mechanism’s role in the development of lung cancer.

The preliminary safety and efficacy data, including progression-free survival (PFS) and overall survival (OS), will be reported on October 29 at the 2013 World Conference on Lung Cancer.

“We look forward to further discussion of the data following its presentation at the conference,” said Eric H. Rubin, MD, the vice president of Oncology at Merck Research Laboratories, the company developing the drug, in a statement.

In the trial, 38 patients with squamous and nonsquamous NSCLC who had received two prior systemic regimens were treated with MK-3475 at 10 mg/kg every three weeks. The median age of patients on the trial was 63 years old. Forty-two percent of patients had an ECOG performance status of zero and 10% of patients had stable, previously treated brain metastases. Additionally, tumor PD-L1 expression was assessed prior to treatment.

According to an abstract published in advance of the meeting, imaging reports were examined every 9 weeks using immune-related response criteria (irRC). In the preliminary findings, ORR was calculated using both confirmed and unconfirmed responses. According to investigator-assessed irRC, ORR was 24%. However, an independent central review using RECIST v1.1 criteria found an ORR of 21%. At a median 9-month follow-up, the median duration of response had not been reached. PD-L1 expression was found to be a statistically significant predictor of response.

All grade adverse events (AEs) occurred in 50% of patients treated with MK-3475, with the most common AEs being fatigue, rash, and pruritus. Additionally, 1 patient developed drug-related grade 3 pulmonary edema.

“These early data in lung cancer patients were the basis for Merck’s decision to rapidly advance MK-3475 into a Phase II/III clinical trial in NSCLC," remarked Rubin in a statement announcing the presentation of these results.

A phase II/III study is currently recruiting and plans to enroll 920 PD-L1-positive patients with NSCLC who have experienced disease progression after platinum-containing systemic therapy. The study will compare a low and high dose of intravenous MK-3475 with docetaxel at 75 mg/m², every 3 weeks. The primary endpoints for both portions of the study are OS, PFS, the number of patients experiencing an adverse event, and the number of patients that discontinue treatment.

Merck recently announced that the company plans to restructure their operations to place more emphasis on potential growth opportunities, such as its anti-PD-1 immunotherapy program. In conjunction with this, the company announced the formation of a new unit focused solely on the development of MK-3475.

In April, MK-3475 received a Breakthrough Therapy designation from the FDA as a treatment for patients with melanoma after promising results from a small single-arm study. The agent is also being explored in a variety of clinical trials as a treatment for patients with bladder cancer, colorectal cancer, head and neck cancer, and triple-negative breast cancer.

Garon EB, Balmanoukian A, Hamid O, et al. Preliminary clinical safety and activity of MK-3475 monotherapy for the treatment of previously treated patients with non-small cell lung cancer (NSCLC). To be presented at: 15th World Conference on Lung Cancer; October 27-October 30, 2013; Sydney, Australia. Abstract 2416.