All of a mind on brain tumor vaccine

TUEBINGEN, Germany—June 2 saw theannouncement that immatics biotechnologies GmbH, a clinical-stagebiopharmaceutical company developing anti-cancer vaccines, has signeda clinical trial agreement with the Center for Cancer Research (CCR)at the National Cancer Institute (NCI) in the United States.Complementing a February deal with Cancer Research UK, this gives theGerman company important agreements with a key oncology organizationacross the pond as well as one just inside it.

The NCI deal covers the clinicaldevelopment of immatics' therapeutic cancer vaccine IMA950, whichis to be evaluated in the field of brain cancer, specificallyglioblastoma, the most aggressive form of brain cancer. CCR willsponsor and conduct a phase I trial of IMA950 to be carried out atthe National Institute of Health's facility in Bethesda, Md., whichwill evaluate IMA950 in stable or recurrence-free glioblastomapatients following standard radiochemotherapy with temozolomide.

This is distinct from the Februaryagreement, under which Cancer Research UK will sponsor and conduct aPhase I trial of IMA950 to be carried out at leading glioma researchcenters in the United Kingdom via its Drug Development Office,treating newly diagnosed patients with IMA950 in combination withradio-chemotherapy, rather than treat patients after successfulradio-chemotherapy with standalone IMA950. For the deal, immaticswill not only supply the drug for the trial and also undertakeimmunomonitoring in the treated patients.

The different protocols for these twostudies should mean that they provide complementary data reflectingthe different clinical situations experienced by glioblastomapatients.

"Our ability to secure two suchhighly regarded collaborators to advance IMA950 into the clinicdemonstrates the significant interest in immatics' noveltherapeutic vaccines and the need for a much improved treatmentoption for glioblastoma," says Paul Higham, CEO of immatics.

After the completion of the U.K. study,immatics will have an exclusive first right to take a license to thedata for further development of IMA950. No financial details weredisclosed with regard to that deal.

The principal investigator of the U.S.study is Dr. Howard Fine, chief of the Neuro-Oncology Branch at NCI.As with the Cancer Research UK deal, immatics will be responsible fordrug supply for the study as well as undertaking immunomonitoring ofthe treated patients.

IMA950 is a therapeutic cancer vaccinegenerated through immatics' proprietary XPRESIDENT technology. Itconsists of 11 tumor-associated peptides that the immatics platformselected on the basis of their natural presentation by tumor tissue,overexpression in tumor versus healthy tissue, immunogenicity andtheir relevance to tumor function.

It is not, however, the only item inthe immatics pipeline with promise. Just three days after announcingthe NCI deal, immatics also announced that results from itsexploratory Phase II clinical trial with IMA901 in patients withadvanced renal cell carcinoma were positive enough that it plans tostart a randomized, controlled pivotal clinical trial with IMA901.

The exploratory Phase II studyrecruited 68 patients with advanced/metastatic renal cell carcinomawho had failed previous first line therapy (either tyrosine kinaseinhibitors or cytokines). Patients in the study were randomized toreceive one single infusion of cyclophosphamide (CY) asimmunomodulator prior to the first vaccination with the multi-peptidevaccine IMA901. The study investigated disease control rate at sixmonths, progression-free survival, overall survival, correlation ofimmune response with clinical benefit and safety and tolerability.

Patients randomized to receive a singledose of CY showed a strong trend towards improved overall survivalversus patients who did not receive CY, and the survival data of thisstudy compares very favorably to previous studies of the approvedtyrosine kinase inhibitors sunitinib and sorafenib.

"The fact that we have seen thispotential survival benefit is important given the regulatoryauthorities' recognition of survival as the key efficacy endpointfor cancer vaccines," Higham says. "Additionally, we haveconfirmed the mechanism of action of IMA901 by demonstrating asignificant association of immune response with clinical benefit intwo independent trials."