Receptor-targeted radionuclide therapy combined with immunotherapies to improve metastatic melanoma tumor response.

Melanoma incidence is rising faster than any other cancerSurgery can be curative at early stagesbut metastatic melanoma is typically fatalResponses to new targeted and immunotherapies can be remarkable in select casesbut low response ratesacquired resistanceand severe adverse side effectsparticularly for combination immunotherapieslimit long term quality of life for these patientsThusdespite what is rightly seen as a revolution in advanced stage melanoma treatmentthe overall response rate to all therapies remains dismally nearand theyear survival is andltDespite these shortcomingsthere is a clear and growing market for advanced melanoma drugsglobal revenues $ Blnexpected CAGRFurtherreceptortargeted radionuclide therapies are emerging as valuable products in oncologyTwo recent acquisitions by large pharmaAlgeta by Bayer in$Blnand Advanced Accelerator Applications by Novartis in$Blnhighlight this valueViewpoint identified an initial indication for its MCRtargeted radionuclide therapy of progressive stagemetastatic melanomapotential global annual revenues $MlnHoweveremerging evidence suggests a synergistic role for ionizing radiationIRcombined with immunotherapy to promote immunogenic cancer cell deathCurrent external beam IR relies on an abscopal effect because IR delivered in this way can only be directed to individual lesionsBecause of known intertumoral heterogeneity of melanomathe advantage of systemic MC R RT is precise deposition of radiation in all metastatic lesionswhich has the potential to improve the repertoire of neoantigens presented to the immune systemThusthere is a critical need to determine the feasibility of safely combining immunotherapies with MC R RT for metastatic melanomaProof of concept study results support the hypothesis that this combination can expand our indication to a front line therapyThe State of Iowa will match $k upon award for this projectBUSINESS RATIONALESuccess in combining MC R RT with immunotherapy to safely improve rates of overall and complete response for malignant melanoma potentially expands our indication to a frontline combination therapy for all metastatic melanoma patientswhich would significantly increase our valuationAIMDetermine the feasibility of safely combining MC R RTYwith immunotherapies to improve tumor response rates and survival in two immune competent mouse melanoma modelsIMPACT and SIGNIFICANCESuccessful completion of this Aim will establish the feasibility of safely combining Viewpoint s proprietary MCRtargeted radionuclide therapy with immunotherapies for malignant melanomaThis work if successful will also establish a robust biochemical and immunological rationale for further development of MC R RT in clinical trials designed to overcome low response ratesacquired resistanceand serious side effects that limit current malignant melanoma therapies This proposal is aims to develop a combination radionuclide therapy for metastatic melanoma that improves tumor response to immunotherapiesNo other agents are available that are based on this approach