Date: 2012-06-01
Type of information: Results
phase: 2
Announcement: results
Company: immatics biotechnologies (Germany)
Product: IMA910
Action
mechanism: IMA910 is a therapeutic cancer vaccine comprising 13 tumor-associated peptides (TUMAPs) that are frequently found to be over-expressed in the majority of patients suffering from colorectal cancer. These TUMAPs were identified based on the analysis of primary tumor tissue and have been chosen due to their ability to activate cytotoxic T cells and T helper cells against colorectal cancer. As with all immatics’ vaccines, IMA910 has been designed to elicit a strong, clinically relevant immune response to a specific tumor type. The TUMAPs were selected from over 2,000 peptides identified via immatics’ unique XPRESIDENT™ platform.
Disease: advanced colorectal cancer
Therapeutic area: Cancer - Oncology
Country: 9 European countries
Trial
details: The IMA910 phase 2 study recruited 92 patients with advanced/metastatic CRC who had shown no progression following 12 weeks of first line oxaliplatin-based chemotherapy and who were on a planned break from their chemotherapy regimen.
In the phase 2 study, patients received one single infusion of cyclophosphamide (CY) as immunomodulator prior to the first vaccination with the multi-peptide vaccine IMA910. They were treated with IMA910 plus GM-CSF and with or without an additional immunomodulator imiquimod. Patients received up to 16 vaccinations with IMA910 over a period of nine months. The trial was conducted at 51 centers in nine European countries.
Latest
news: * On June 1, 2012, immatics biotechnologies GmbH, a clinical-stage biopharmaceutical company developing advanced therapeutic vaccines that are active against cancer, has announced that its phase 2 trial with IMA910 in patients with advanced colorectal cancer (CRC) showed significantly longer overall survival in comparison to a matched-pair analysis of patients from the recently published phase 3 MRC COIN trial. The immatics study also showed that patients who developed immune responses to two or more of the tumor associated peptides (TUMAPs) in IMA910 correlate with longer overall survival times. These data were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, USA.
The overall survival in IMA910 treated patients was compared to patients enrolled in one arm (C) of the MRC COIN trial* using a pre-planned independent results-blinded matched-pair analysis. In common with the IMA910 patients, patients in the C arm of the COIN study had also shown no progression following 12 weeks of first line oxaliplatin-based chemotherapy and were on a planned break from the intermittent chemotherapy regimen set out in the study protocol. The independent, blind, matched-pair analysis was carried out to eliminate potential differences in baseline characteristics and prognostic factors and to provide a near identical population for the study’s overall survival analysis. The COIN trial, which recruited close to 2,500 patients, is the largest study to-date in patients with advanced CRC and was designed to assess the relative benefits of three different treatment regimens one of which involved the use of intermittent chemotherapy treatment.
In the immatics’ phase 2 study, patients treated with IMA910 had a median survival of 19.7 months compared to the 16.5 months median survival seen in the matched patients from the COIN study when following from the start of 1st-line chemotherapy. The Hazard Ratio (HR) was 0.665 (p=0.0386). The patients treated with IMA910 also had higher one year (69% versus 55%) and two year (40% versus 24%) survival rates.
In addition and as shown in two previous immatics clinical studies (with IMA901 in renal cell carcinoma), this study demonstrated that in patients who had detectable T-cell responses against two or more TUMAPs – the so-called multi-peptide responders – there was a clear association between the immune response and clinical outcome. In this study the multi-peptide responders to IMA910 had a clinically relevant longer overall survival compared to the matched COIN patients irrespective of the type of immune response (multi-peptide CD8 T-cell responders vs. COIN HR 0.53, p=0.038; multi-peptide CD4 T-cell responders vs. COIN HR 0.53, p=0.016; combined multi-peptide CD8 and CD4 responders HR 0.45, p=0.04) while the non-multi-peptide responders had similar survival compared to the matched COIN patients.
* On January 24, 2012, immatics biotechnologies GmbH has announced positive results from its Phase II clinical trial with IMA910 in patients with advanced colorectal cell carcinoma (CRC) which were presented at the Gastrointestinal Cancers Symposium of the 2012 American Society of Clinical Oncology (ASCO) in San Francisco.
The data from the study confirmed that IMA910 is able to stimulate relevant immune responses against the tumor-associated peptides (TUMAPS) in IMA910 in the majority of patients vaccinated. Intriguingly, when looking at the clinical outcome of patients who had detectable T-cell responses against two or more of the tumor-derived peptides (TUMAPs) contained in IMA910, a consistently better clinical outcome (disease control, progression-free survival and overall survival) was observed compared to those who did not have a detectable multi-T-cell response.
Moreover patients who mounted both CD8+ and CD4+ multi-T-cell responses did not reach the median survival after more than 28 months of follow-up compared to a 16 months median survival time in those who did not (HR 0.53; p=0.088). In addition, the data presented show that IMA910 is very well tolerated with injection-site reactions being the most frequent side effect seen.
