immatics biotechnologies GmbH, a clinical-stage biopharmaceutical company developing advanced therapeutic vaccines that are active against cancer, 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 enrol 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.
Paul Higham, CEO of immatics, said: “We are extremely pleased that Pfizer has committed to supporting our pivotal phase III trial with IMA901 with the supply of Sutent. Their decision reflects the growing interest in IMA901 and its potential to be an important breakthrough in the treatment of renal cell carcinoma patients.”
IMA901 has generated encouraging overall survival data, which compare favourably with historical comparisons of currently available treatments, in a phase II trial in advanced renal cell carcinoma patients. Importantly, the phase II study also showed an association between survival and the patient's immune response to IMA901, as well as confirming the favourable safety profile observed in an earlier phase I study.
“Pfizer is pleased to provide Sutent to support immatic's clinical development program in advanced renal cell carcinoma patients,” said Craig Eagle, vice president of Strategic Alliances and Partnerships for Pfizer Oncology. “This collaboration underscores Pfizer's ongoing commitment to the discovery, investigation and development of innovative treatment options to improve the outlook for cancer patients worldwide.”
IMA901 is a therapeutic cancer vaccine comprising 10 Tumour-Associated Peptides (TUMAPs) that are frequently found to be over-expressed in the majority of patients suffering from renal cell carcinoma. As with all immatics' vaccines, IMA901 has been designed to elicit a strong, clinically relevant immune response to a specific tumour type. The TUMAPs were selected from over 2,000 peptides identified via immatics' unique Xpresident platform. TUMAPs included in IMA901 are from targets with vital functions for the tumour, for example invasion, neo-angiogenesis.
Sutent is an oral multi-kinase inhibitor approved for the treatment of advanced/metastatic Renal Cell Carcinoma (RCC), unresectable and/or metastatic malignant Gastrointestinal Stromal Tumour (GIST) after failure of imatinib mesilate treatment due to resistance or intolerance.
In Europe, Sutent is also indicated for the treatment of unresectable or metastatic, well-differentiated pancreatic neuroendocrine tumours with disease progression in adults. Experience with Sutent as first-line treatment is limited.
Sutent works by blocking multiple molecular targets implicated in the growth, proliferation and spread of cancer. Two important Sutent targets, Vascular Endothelial Growth Factor Receptor (VEGFR) and Platelet-Derived Growth Factor Receptor (PDGFR), are expressed by many types of solid tumours and are thought to play a crucial role in angiogenesis, the process by which tumours acquire blood vessels, oxygen and nutrients needed for growth. It also inhibits other targets important to tumour growth, including KIT, FLT3 and RET.
Hepatotoxicity has been observed in clinical trials and post-marketing experience. Cases of hepatic failure, some with a fatal outcome, were observed in <1% of solid tumour patients treated with Sutent. It is recommended to monitor liver function tests before initiation of treatment, during each cycle of treatment, and as clinically indicated. If signs or symptoms of hepatic failure are present, sunitinib should be discontinued and appropriate supportive care should be provided.
Women of child bearing age who are (or become) pregnant during therapy should be informed of the potential for fetal harm while on Sutent. Decreases in Left Ventricular Ejection Fraction (LVEF) to below the Lower Limit of Normal (LLN) has been observed. Patients with concomitant cardiac conditions should be carefully monitored for clinical signs and symptoms of congestive heart failure. Patients should be monitored for hypertension and treated as needed with standard anti-hypertensive therapy. Complete Blood Counts (CBCs) with platelet count and serum chemistries should be performed at the beginning of each treatment cycle for patients receiving treatment with Sutent.
The most common adverse reactions in GIST, RCC and pancreatic NET clinical trials were diarrhoea, fatigue, asthenia, nausea, mucositis/stomatitis, anorexia, vomiting, neutropenia, hypertension, dyspepsia, abdominal pain, constipation, rash, hand-foot syndrome, skin discolouration, hair colour changes, altered taste and bleeding.
immatics biotechnologies is a clinical-stage biopharmaceutical company developing rationally designed therapeutic vaccines that are active against cancer. immatics' lead product, IMA901, has completed a successful phase II trial in renal cell carcinoma. immatics' pipeline also includes IMA910, in phase II for colorectal cancer, and IMA950 which is in phase I for glioma.