MOLOGEN AG: Initiation of Phase III IMPALA Study with Immunotherapy MGN1703 in Colorectal Cancer

The gist: The first patient has been enrolled in a new clinical trial—a research study with volunteer patients. The goal of the trial is to test whether a new drug can keep cancer from returning (recurrence) in people who were treated for metastatic colorectal cancer. MGN1703 is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer.

“MOLOGEN AG has enrolled the first patient in the international IMPALA study. Primary objective of the phase III pivotal trial is to prove that a switch maintenance therapy with the cancer immunotherapy MGN1703 leads to an increased overall survival (OS) in patients with metastatic colorectal carcinoma.

“IMPALA is a randomized, international, multicenter and controlled phase III trial expected to recruit about 540 patients from more than 100 European centers in eight European countries, including the five major pharma markets. The primary endpoint is overall survival. Secondary study endpoints include progression-free survival, Quality of Life (QoL) as well as safety and tolerability.

“ We are pleased that we have already enrolled the first patient in the IMPALA trial. We are excited to learn more about the efficacy of the novel immunotherapy MGN1703,’ said Prof. David Cunningham, MD, Department of Medicine and Director of Clinical Research, Royal Marsden Hospital in London. ‘The trial aims to confirm the trend in overall survival along with very good safety and tolerability of MGN1703 as observed in the IMPACT trial.’ ”


No Difference in Response Rate but Overall Survival Benefit With First-Line FOLFIRI/Cetuximab vs FOLFIRI/Bevacizumab in Metastatic Colorectal Cancer

Editor’s note: Researchers organized a clinical trial with volunteer patients to compare two treatments for people with metastatic colorectal cancer. All patients in the trial took a chemotherapy treatment called FOLFIRI. (FOLFIRI combines the drugs fluorouracil, leucovorin, and irinotecan.) Some of the patients were also given the drug cetuximab, and the rest took the drug bevacizumab along with FOLFIRI. The patients who took FOLFIRI plus cetuximab survived significantly longer than the patients who took FOLFIRI plus bevacizumab.

“In a European phase III FIRE-3 trial reported in The Lancet Oncology, Heinemann et al found no difference in response rate, the primary endpoint, between FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus the anti-EGFR antibody cetuximab (Erbitux) vs FOLFIRI plus the anti-VEGF-A antibody bevacizumab (Avastin) in first-line treatment of patients with metastatic colorectal cancer. The cetuximab-containing regimen was associated with a significant overall survival advantage…

“In this open-label trial, 592 patients with KRAS exon 2 codon 12/13 wild-type metastatic colorectal cancer aged 18 to 75 years from centers in Germany and Austria were randomly assigned between January 2007 and September 2012 to receive FOLFIRI plus either cetuximab (n = 297) or bevacizumab (n = 295). The primary endpoint was objective response in the intention-to-treat population. The study has completed recruitment, but patient follow-up is ongoing.”


Phase III Trial Shows Improved Survival with TAS-102 in Metastatic Colorectal Cancer Refractory to Standard Therapies

“The new combination agent TAS-102 is able to improve overall survival compared to placebo in patients whose metastatic colorectal cancer is refractory to standard therapies, researchers said.

” ‘Around 50% of patients with colorectal cancer develop metastases but eventually many of them do not respond to standard therapies,’ said Takayuki Yoshino of the National Cancer Centre Hospital East in Chiba, Japan, lead author of the phase III RECOURSE trial. ‘The RECOURSE study shows that TAS-102 improves overall survival in these patients compared to placebo. I believe that this agent will become one of the standards of care in the refractory setting of metastatic colorectal cancer in Japan and worldwide.’

“TAS-102 is a novel nucleoside anti-tumour agent consisting of trifluridine (FTD) and tipiracil hydrochloride (TPI). FTD is the active component of TAS-102 and is directly incorporated into cancer DNA, leading to DNA dysfunction. However, when FTD is taken orally it is largely degraded to an inactive form. TPI prevents the degradation of FTD. This mechanism of action is different to that of fluoropyrimidine, oxaliplatin and irinotecan…

“Douillard concluded: ‘In RECOURSE, TAS-102 was tested in patients who had received all types of chemotherapy available for colorectal cancer. I would probably move this drug into an earlier line of treatment and I would also combine it with either irinotecan or oxaliplatin.’ ”

Editor’s note: This story discusses the results of a clinical trial that tested a new treatment for colorectal cancer in volunteer patients. The trial tested whether the treatment—called TAS-102—benefits people with metastatic cancer that has not responded to standard treatment. Some patients in the trial were treated with TAS-102, and for comparison, some were given a “fake” placebo treatment. The results showed that patients treated with TAS-102 survived longer than patients who took the placebo.