immatics Presents Encouraging Overall Survival Data from a Phase 2 Study in CRC
News Jun 04, 2012
immatics biotechnologies GmbH 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. IMA910 is a cancer vaccine comprising 13 rationally selected TUMAPs identified directly from primary colorectal tumor tissue.
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.
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.
Professor Tim Maughan, Professor of Clinical Oncology and Director of the MRC/CR-UK Gray Institute for Radiation Oncology, University of Oxford and the Chief Investigator of the COIN study said: “The overall survival data generated with IMA910 in this phase 2 trial are very encouraging. The blind, matched-pair analysis with patients in the intermittent chemotherapy arm of the COIN study has produced a very comparable patient group for assessing the overall survival endpoint of this study. I believe these excellent results warrant further clinical development of IMA910 in patients with colorectal cancer.”
The phase 2 trial also showed that IMA910 is very well tolerated with mild-moderate injection-site reactions being the most frequent side effect.
Paul Higham, CEO of immatics said: “The improvement in overall survival that we have seen when compared to matched patients in the COIN study is extremely encouraging. Importantly, the immune-monitoring data we have generated show a clear and significant improvement on the overall survival of patients who mount an immune response to two or more of the TUMAPs in IMA910. Given these positive results we are currently assessing the best way to continue the further development of this novel and exciting therapeutic cancer vaccine which could become a 1st line standard treatment for patients with colorectal cancer.”
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.
The posters presented and discussed by experts at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago contain a more detailed analysis of the overall survival, safety and immune response data generated with IMA910 in this phase 2 study. The posters can be downloaded at www.immatics.com.
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