Date: 2015-07-27
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the European Society for Medical Oncology (ESMO) 2015 congress
Company: Immatics Biotechnologies (Germany)
Product: IMA901 and sunitinib
Action
mechanism: kinase inhibitor/peptide. IMA901 is composed of ten synthetic tumor-associated peptides (TUMAPs), which activate the body’s own killer T-cells against the tumor. Unlike chemotherapy, this process targets the body’s immune responses and mobilizes them to attack the cancer.
Disease: metastatic renal cell carcinoma (RCC)
Therapeutic area: Cancer - Oncology
Country:
Trial
details: IMPRINT is a global multicenter, randomized, controlled Phase III study in patients with metastatic and/or locally advanced RCC who are candidates for receiving standard first-line therapy with sunitinib (Sutent®,Pfizer). The trial will include approximately 330 patients across the US and Europe.The primary endpoint of the Phase III study is overall survival in patients receiving IMA901 in combination with sunitinib versus sunitinib alone. Overall survival will also be tested in patients who are positive for a prospectively defined biomarker signature. This signature was identified as being predictive for improved clinical outcome in IMA901-vaccinated patients in the previous Phase II study. Details on the biomarker signature were presented in the plenary session of the Annual Meeting of Association for Cancer Immunotherapy (CIMT) in late May 2011.Further secondary endpoints include progression-free survival, safety and tolerability, and cellular immunomonitoring to assess the T-cell response to the peptides contained in IMA901. Data from the reported Phase II trial showed that the intensity of the immune response against the IMA901 TUMAPS vaccine was predictive for improved overall survival.
Latest
news: * On September 27, 2015, Immatics Biotechnologies announced the results of a pivotal phase 3 clinical trial with IMA901 in patients with metastatic renal cell carcinoma (RCC) in combination with sunitinib. Results were presented by Dr. Brian Rini, Professor of Medicine at the Cleveland Clinic Taussig Cancer Center and Chief Investigator of the phase 3 trial at the European Society of Medical Oncology (ESMO) Meeting in Vienna, Austria. The phase 3 trial did not meet its primary endpoint of showing an overall survival benefit of IMA901 in combination with sunitinib compared with sunitinib alone in this patient population.
The phase 3 trial had been designed to demonstrate an overall survival (OS) benefit in patients receiving IMA901 in combination with the standard first-line therapy sunitinib versus sunitinib alone, in patients with metastatic and/or locally advanced RCC. 339 patients were randomized 3:2 to receive or not up to 10 intradermal vaccinations of IMA901 plus 75 µg GM-CSF in addition to sunitinib; a single infusion of cyclophosphamide (300mg/m2) was given three days prior to the first vaccination to reduce the patient’s regulatory T cells. The primary endpoint of the phase 3 study was OS with progression free survival (PFS), overall response rate (ORR), safety, with biomarker and immune analyses being secondary endpoints. No significant difference in OS was found when IMA901 was added to sunitinib standard first line treatment for patients with metastatic RCC. The study did not demonstrate an association between T-cell responses and clinical outcomes – in contrast to the phase 2 trial with IMA901, which demonstrated a clear link between the patient’s T cell response and OS.
The intensity of the immune responses observed in the phase 3 trial when combined with sunitinib was shown to be 3-fold lower than those observed in the previous phase 2 trial, when IMA901 was investigated as single agent. The trial confirmed that IMA901 had a favorable safety profile with transient injection-site reactions being the most frequent IMA901-related side effect.
Dr. Carsten Reinhardt, Chief Medical Officer of Immatics, said: “It is disappointing that the phase 3 trial did not generate the anticipated overall survival benefit. We will continue to review the data to gain a better understanding of these results. The observation that the magnitude of immune responses was significantly below expectations based on the previous results of IMA901, when acting as a single agent, may partly explain that clinical finding and asks for better means of mounting active immune cells against relevant cancer targets. (...) It is our intention to focus our development efforts from now on our novel Adoptive Cellular Therapies through our recently announced major collaboration with MD Anderson Cancer Center.”* On November 8, 2012, immatics biotechnologies, a biopharmaceutical company developing rationally designed therapeutic vaccines that are active against cancer, has announced that it has completed patient recruitment into the pivotal phase 3 trial evaluating its lead cancer vaccine IMA901 for renal cell carcinoma (RCC). The trial has completed patient inclusion and it is expected that around 345 patients will be randomized across 10 countries in the US and Europe. The first (interim) overall survival results are expected during the first half of 2014.In addition, immatics announced that IMA901 has been granted orphan drug designation from the FDA for the treatment of renal cell carcinoma in HLA-A*02 positive patients.* On June 15, 2011, immatics biotechnologies has announced that the first patients have been vaccinated in the IMPRINT study, a pivotal Phase III trial with IMA901, the company’s lead cancer vaccine for the treatment of renal cell carcinoma (RCC).The trial is designed to demonstrate the overall survival benefit of IMA901 in combination with standard first-line therapy in RCC patients. The study builds on the promising survival and immune response data observed in the Phase II study with IMA901 in advanced RCC patients. Data from the Phase II study were presented at ASCO in June 2010 and at ESMO in October 2010.The first overall survival results of the study are expected in late 2013. The chief investigator of the trial is Professor Brian Rini, Associate Director for Clinical Research at the Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio and Professor Tim Eisen, Clinical Director of Medical Oncology at Addenbrooke´s Hospital, University of Cambridge, UK, is the European lead investigator.* On April 11, 2011, immatics biotechnologies has announced that Pfizer has agreed to support its pivotal Phase III trial (IMPRINT = IMA901 Multi-Peptide vaccine Randomized INTernational study) with IMA901, its therapeutic cancer vaccine for advanced renal cell carcinoma. The pivotal Phase III study will evaluate as the primary endpoint the overall survival of advanced renal cell carcinoma patients treated with IMA901 in combination with Pfizer’s Sutent® (sunitinib malate) versus Sutent® alone. The study is expected to enroll approximately 330 patients across Europe and in the US.Pfizer will support the trial by supplying Sutent® for all the patients enrolled in the pivotal study. The first patients are expected to start treatment in April 2011.
