Merck Serono will discontinue its worldwide clinical development program of MUC1 antigen-specific immunotherapy tecemotide as a monotherapy in stage III non-small cell lung cancer. This includes the phase III START2 and INSPIRE studies.
The decision comes after a planned analysis of EMR 63325-009, a randomized, double-blind, placebo-controlled phase I/II study in Japanese patients with stage III unresectable, locally advanced NSCLC. Patients had received concurrent or sequential chemoradiotherapy with a minimum of two cycles of platinum-based chemotherapy and radiation dose greater than or equal to 50 Gy.
Of the patients included in the phase II part of the study, the majority had received concurrent CRT. No effect has been observed for either the primary endpoint of overall survival, or for any of the secondary endpoints, including progression-free survival, time to progression, and time to treatment failure.
An analysis of the reported adverse events has not identified a clinically meaningful difference in the frequency between treatment groups. Although the trial was not powered to demonstrate a statistically significant difference in benefit between the two arms, Merck Serono made the recommendation to stop the investigational treatment for patients in the EMR 63325-009 study.
“While the data from the exploratory subgroup analysis in the START trial generated a reasonable hypothesis to warrant additional study, the results of the recent trial in Japanese patients decreased the probability of current studies to reach their goals,” said Luciano Rossetti, global head of research and development at Merck Serono.
The START2 study is a 1:1 randomized, double-blind, placebo-controlled clinical trial in unresectable, stage IIIA or IIIB NSCLC who have had a response or stable disease after at least two cycles of platinum-based concurrent CRT.
The study, which began in April 2014, was expected to recruit about 1,000 patients.
The initial START study did not meet the primary endpoint of demonstrating an improved OS with tecemotide compared with placebo in the overall patient population (n=1,239). Median OS was 25.6 months for patients in the tecemotide group compared with 22.3 months for those in the placebo group (adjusted HR: 0.88; 95% CI: 0.75-1.03; p=0.123).
However, data from an exploratory analysis of a pre-defined subgroup of patients in the START trial—patients who received tecemotide after concurrent CRT—showed that these patients achieved a median OS of 30.8 months compared to 20.6 months in patients treated with placebo (n=806; HR: 0.78; 95% CI: 0.64-0.95; p=0.016).
INSPIRE is a multicenter, randomized, double-blind, placebo-controlled clinical trial in unresectable, locally advanced stage IIIA or IIIB NSCLC patients who have had a response or stable disease after at least two cycles of platinum-based concurrent CRT. INSPIRE expected to recruit approximately 500 stage III NSCLC patients across China, Hong Kong, Korea, Singapore and Taiwan.
Patients on active treatment with tecemotide can undergo an individual assessment by their treating physician and apply to receive further treatment outside of the studies. Merck will continue to supply tecemotide for ongoing investigator-sponsored trials in other indications in accordance with the company’s agreements with the sponsors of these studies.
Merck obtained the exclusive worldwide rights for development and commercialization of tecemotide from Oncothyreon Inc. in 2007, in an agreement replacing prior collaboration and supply agreements originally entered in 2001. In Japan, Merck entered into a co-development and co-marketing agreement for tecemotide with Ono Pharmaceutical Co., Ltd.
