Merck Serono announces PHASE III START trial results in the Lancet

Data included in the publication1, and first presented at the American Society of Clinical Oncology (ASCO) 20132, showed that the primary endpoint of overall survival (OS) was not met. 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). The publication includes an exploratory analysis of a predefined subgroup of patients in the START trial who received tecemotide after concurrent chemoradiotherapy (CRT).(1)

Concurrent CRT is a combination of chemotherapy and radiotherapy given at the same time. Patients in this subgroup achieved a median OS of 30.8 months vs. 20.6 months in patients treated with placebo (n=806; HR: 0.78; 95% CI 0.64-0.95; p=0.016).(1) In patients receiving sequential CRT followed by tecemotide or placebo a median OS of 19.4 months was observed for the tecemotide group compared with 24.6 months for the placebo group (n=433; HR 1.12; 95% CI 0.87–1.44; p=0.38).

“These results have generated considerable interest within the scientific community and we hope that the publication will provide additional context to help inform future immuno-oncology research,” said Dr. Charles Butts, Cross Cancer Institute, University of Alberta, Edmonton, Canada, clinical investigator of the START trial and member of the corresponding steering committee. “In the article we have hypothesised potential reasons why the combination with concurrent CRT demonstrated increased overall survival in START compared to combination with sequential CRT and we look forward to investigating tecemotide further to determine if it is a suitable therapeutic option that could help deliver positive outcomes for patients.”

As previously announced, Merck Serono will continue the development of tecemotide under a new Phase III trial called START2, based on the results of the START trial. The START2 trial is a multicentre, randomised, double-blind, placebo-controlled trial designed to assess the efficacy, safety and tolerability of tecemotide in patients suffering from unresectable, locally advanced (Stage IIIA or IIIB) NSCLC who have had a response or stable disease after at least two cycles of platinum-based concurrent CRT.

Concurrent CRT is the standard of care for these patients. The trial’s primary endpoint is OS. Merck has received Scientific Advice from the European Medicines Agency (EMA) on the program, and has reached an agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for the Phase III international randomised trial.

Dr. Annalisa Jenkins, Head of Global Head of Global Research and Development for Merck Serono, said: “The publication of the START trial confirms the interest of the scientific medical community in the potential that immunotherapy may offer for patients living with lung cancer. We continue to pursue development of tecemotide in the hope that it can potentially bring meaningful benefit for patients fighting this devastating disease.”

Tecemotide is an investigational MUC1 antigen-specific cancer immunotherapy designed to stimulate the body’s immune system to identify and target cancer cells expressing the cell-surface glycoprotein MUC1.(3,4) MUC1 is expressed in many cancers, including NSCLC, and has multiple roles in tumour growth and survival.(3,5)

Globally, lung cancer is the most common cause of cancer-related deaths in men and the second most common in women, responsible for almost twice as many deaths as both breast and prostate cancer combined.(6) NSCLC is the most common type of lung cancer, accounting for 80–85% of all lung cancers, and locally advanced or Stage III disease accounts for approximately 30% of patients with NSCLC.(7,8) Unfortunately, at diagnosis, most patients have advanced or metastatic disease with a very poor prognosis.(9) There is an especially urgent and ongoing need for new approaches for patients with advanced, unresectable NSCLC.