Not listed COMBINING RECEPTOR-TARGETED ALPHA PARTICLE THERAPY AND IMMUNOTHERAPY TO ACHIEVE COMPLETE RESPONSES IN METASTATIC MELANOMA - REVISED. METASTATIC MELANOMA IS A LETHAL DISEASE BECAUSE LOW RESPONSE RATES (NEAR 50%), ACQUIRED RESISTANCE, AND SEVERE ADVERSE SIDE EFFECTS LIMIT LONG-TERM QUALITY OF LIFE FOR THESE PATIENTS (5-YR. SURVIVAL $13M SERIES A SECURED; IND FOR [203PB]VMT01 PHASE 1 MELANOMA IMAGING TRIAL SECURED (MAYO CLINIC; IND#152145); COMPLETED PRE-IND CONSULTATION WITH FOR [212PB]VMT01 MONOTHERAPY AND AGENCY IS IN SUPPORT OF VIEWPOINT APPROACH (IND#156357; SEE LETTERS); IP LICENSED (EXCLUSIVE); ISOTOPE SUPPLY 203PB/212PB SECURED; PROTOTYPE 212PB PRODUCTION DEVICE (VMT-A-GEN) COMPLETED; ESTABLISHED VMT-A-GEN MFG FACILITIES TO CONTROL 212PB SUPPLY. PHARM/TOX/DOSIMETRY IN MICE FOR VMT01 COMPLETE. COMPLETING THE REVISED SPECIFIC AIMS READIES VIEWPOINT FOR COMBINED [212PB]VMT01 A-RT WITH ICI CLINICAL TRIALS FOR METASTATIC MELANOMA. AIM 1 (VIEWPOINT LAB): DEVELOP A DETAILED UNDERSTANDING OF THE REGIMENS OF [212PB]VMT01 PLUS IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES WITH MINIMAL TOXICITIES IN IMMUNE-COMPETENT MICE. REVISED INCLUDES TOXICITY RESPONSE TO ICI'S, TIMING OF ADMINISTRATIONS, AND ABSCOPAL EFFECTS. AIM 2 (MORRIS LAB/UNIVERSITY OF WISCONSIN): DEVELOP A DETAILED UNDERSTANDING OF THE IMMUNOMODULATING EFFECT OF [212PB]VMT01 IN TWO SYNGENEIC MELANOMA MODELS WITH HETEROGENOUS EXPRESSION OF MC1R. IMPACT AND SIGNIFICANCE: BY COMPLETING THIS PROJECT, WE EXPECT TO HAVE IDENTIFIED DOSING REGIMENS FOR SYSTEMIC [212PB]VMT01 A-RT WITH IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES, WHILE MINIMIZING TOXICITIES IN 4 IMMUNE-COMPETENT MOUSE MODELS. WE FURTHER EXPECT TO HAVE DEVELOPED UNDERSTANDING OF THE SYSTEMIC ANTI-TUMOR IMMUNE RESPONSE FOR PRIMARY AND METASTATIC TUMORS THAT CAPTURES KNOWN INTERTUMORAL HETEROGENEITY OF METASTATIC MELANOMA. WE ANTICIPATE THAT THIS WILL LEAD TO CLINICAL TRIALS AND A NEW APPROACH TO METASTATIC MELANOMA PATIENT CARE THAT RESULTS IN MORE COMPLETE RESPONSES AND BETTER QUALITY OF LIFE. $0 9/15/25 Not listed COMBINING RECEPTOR-TARGETED ALPHA PARTICLE THERAPY AND IMMUNOTHERAPY TO ACHIEVE COMPLETE RESPONSES IN METASTATIC MELANOMA - REVISED. METASTATIC MELANOMA IS A LETHAL DISEASE BECAUSE LOW RESPONSE RATES (NEAR 50%), ACQUIRED RESISTANCE, AND SEVERE ADVERSE SIDE EFFECTS LIMIT LONG-TERM QUALITY OF LIFE FOR THESE PATIENTS (5-YR. SURVIVAL $13M SERIES A SECURED; IND FOR [203PB]VMT01 PHASE 1 MELANOMA IMAGING TRIAL SECURED (MAYO CLINIC; IND#152145); COMPLETED PRE-IND CONSULTATION WITH FOR [212PB]VMT01 MONOTHERAPY AND AGENCY IS IN SUPPORT OF VIEWPOINT APPROACH (IND#156357; SEE LETTERS); IP LICENSED (EXCLUSIVE); ISOTOPE SUPPLY 203PB/212PB SECURED; PROTOTYPE 212PB PRODUCTION DEVICE (VMT-A-GEN) COMPLETED; ESTABLISHED VMT-A-GEN MFG FACILITIES TO CONTROL 212PB SUPPLY. PHARM/TOX/DOSIMETRY IN MICE FOR VMT01 COMPLETE. COMPLETING THE REVISED SPECIFIC AIMS READIES VIEWPOINT FOR COMBINED [212PB]VMT01 A-RT WITH ICI CLINICAL TRIALS FOR METASTATIC MELANOMA. AIM 1 (VIEWPOINT LAB): DEVELOP A DETAILED UNDERSTANDING OF THE REGIMENS OF [212PB]VMT01 PLUS IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES WITH MINIMAL TOXICITIES IN IMMUNE-COMPETENT MICE. REVISED INCLUDES TOXICITY RESPONSE TO ICI'S, TIMING OF ADMINISTRATIONS, AND ABSCOPAL EFFECTS. AIM 2 (MORRIS LAB/UNIVERSITY OF WISCONSIN): DEVELOP A DETAILED UNDERSTANDING OF THE IMMUNOMODULATING EFFECT OF [212PB]VMT01 IN TWO SYNGENEIC MELANOMA MODELS WITH HETEROGENOUS EXPRESSION OF MC1R. IMPACT AND SIGNIFICANCE: BY COMPLETING THIS PROJECT, WE EXPECT TO HAVE IDENTIFIED DOSING REGIMENS FOR SYSTEMIC [212PB]VMT01 A-RT WITH IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES, WHILE MINIMIZING TOXICITIES IN 4 IMMUNE-COMPETENT MOUSE MODELS. WE FURTHER EXPECT TO HAVE DEVELOPED UNDERSTANDING OF THE SYSTEMIC ANTI-TUMOR IMMUNE RESPONSE FOR PRIMARY AND METASTATIC TUMORS THAT CAPTURES KNOWN INTERTUMORAL HETEROGENEITY OF METASTATIC MELANOMA. WE ANTICIPATE THAT THIS WILL LEAD TO CLINICAL TRIALS AND A NEW APPROACH TO METASTATIC MELANOMA PATIENT CARE THAT RESULTS IN MORE COMPLETE RESPONSES AND BETTER QUALITY OF LIFE. $948.1k 6/28/23 Not listed COMBINING RECEPTOR-TARGETED ALPHA PARTICLE THERAPY AND IMMUNOTHERAPY TO ACHIEVE COMPLETE RESPONSES IN METASTATIC MELANOMA - REVISED. METASTATIC MELANOMA IS A LETHAL DISEASE BECAUSE LOW RESPONSE RATES (NEAR 50%), ACQUIRED RESISTANCE, AND SEVERE ADVERSE SIDE EFFECTS LIMIT LONG-TERM QUALITY OF LIFE FOR THESE PATIENTS (5-YR. SURVIVAL $13M SERIES A SECURED; IND FOR [203PB]VMT01 PHASE 1 MELANOMA IMAGING TRIAL SECURED (MAYO CLINIC; IND#152145); COMPLETED PRE-IND CONSULTATION WITH FOR [212PB]VMT01 MONOTHERAPY AND AGENCY IS IN SUPPORT OF VIEWPOINT APPROACH (IND#156357; SEE LETTERS); IP LICENSED (EXCLUSIVE); ISOTOPE SUPPLY 203PB/212PB SECURED; PROTOTYPE 212PB PRODUCTION DEVICE (VMT-A-GEN) COMPLETED; ESTABLISHED VMT-A-GEN MFG FACILITIES TO CONTROL 212PB SUPPLY. PHARM/TOX/DOSIMETRY IN MICE FOR VMT01 COMPLETE. COMPLETING THE REVISED SPECIFIC AIMS READIES VIEWPOINT FOR COMBINED [212PB]VMT01 A-RT WITH ICI CLINICAL TRIALS FOR METASTATIC MELANOMA. AIM 1 (VIEWPOINT LAB): DEVELOP A DETAILED UNDERSTANDING OF THE REGIMENS OF [212PB]VMT01 PLUS IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES WITH MINIMAL TOXICITIES IN IMMUNE-COMPETENT MICE. REVISED INCLUDES TOXICITY RESPONSE TO ICI'S, TIMING OF ADMINISTRATIONS, AND ABSCOPAL EFFECTS. AIM 2 (MORRIS LAB/UNIVERSITY OF WISCONSIN): DEVELOP A DETAILED UNDERSTANDING OF THE IMMUNOMODULATING EFFECT OF [212PB]VMT01 IN TWO SYNGENEIC MELANOMA MODELS WITH HETEROGENOUS EXPRESSION OF MC1R. IMPACT AND SIGNIFICANCE: BY COMPLETING THIS PROJECT, WE EXPECT TO HAVE IDENTIFIED DOSING REGIMENS FOR SYSTEMIC [212PB]VMT01 A-RT WITH IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES, WHILE MINIMIZING TOXICITIES IN 4 IMMUNE-COMPETENT MOUSE MODELS. WE FURTHER EXPECT TO HAVE DEVELOPED UNDERSTANDING OF THE SYSTEMIC ANTI-TUMOR IMMUNE RESPONSE FOR PRIMARY AND METASTATIC TUMORS THAT CAPTURES KNOWN INTERTUMORAL HETEROGENEITY OF METASTATIC MELANOMA. WE ANTICIPATE THAT THIS WILL LEAD TO CLINICAL TRIALS AND A NEW APPROACH TO METASTATIC MELANOMA PATIENT CARE THAT RESULTS IN MORE COMPLETE RESPONSES AND BETTER QUALITY OF LIFE. $976.7k 6/29/22 Not listed COMBINING RECEPTOR-TARGETED ALPHA PARTICLE THERAPY AND IMMUNOTHERAPY TO ACHIEVE COMPLETE RESPONSES IN METASTATIC MELANOMA - REVISED. METASTATIC MELANOMA IS A LETHAL DISEASE BECAUSE LOW RESPONSE RATES (NEAR 50%), ACQUIRED RESISTANCE, AND SEVERE ADVERSE SIDE EFFECTS LIMIT LONG-TERM QUALITY OF LIFE FOR THESE PATIENTS (5-YR. SURVIVAL $13M SERIES A SECURED; IND FOR [203PB]VMT01 PHASE 1 MELANOMA IMAGING TRIAL SECURED (MAYO CLINIC; IND#152145); COMPLETED PRE-IND CONSULTATION WITH FOR [212PB]VMT01 MONOTHERAPY AND AGENCY IS IN SUPPORT OF VIEWPOINT APPROACH (IND#156357; SEE LETTERS); IP LICENSED (EXCLUSIVE); ISOTOPE SUPPLY 203PB/212PB SECURED; PROTOTYPE 212PB PRODUCTION DEVICE (VMT-A-GEN) COMPLETED; ESTABLISHED VMT-A-GEN MFG FACILITIES TO CONTROL 212PB SUPPLY. PHARM/TOX/DOSIMETRY IN MICE FOR VMT01 COMPLETE. COMPLETING THE REVISED SPECIFIC AIMS READIES VIEWPOINT FOR COMBINED [212PB]VMT01 A-RT WITH ICI CLINICAL TRIALS FOR METASTATIC MELANOMA. AIM 1 (VIEWPOINT LAB): DEVELOP A DETAILED UNDERSTANDING OF THE REGIMENS OF [212PB]VMT01 PLUS IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES WITH MINIMAL TOXICITIES IN IMMUNE-COMPETENT MICE. REVISED INCLUDES TOXICITY RESPONSE TO ICI'S, TIMING OF ADMINISTRATIONS, AND ABSCOPAL EFFECTS. AIM 2 (MORRIS LAB/UNIVERSITY OF WISCONSIN): DEVELOP A DETAILED UNDERSTANDING OF THE IMMUNOMODULATING EFFECT OF [212PB]VMT01 IN TWO SYNGENEIC MELANOMA MODELS WITH HETEROGENOUS EXPRESSION OF MC1R. IMPACT AND SIGNIFICANCE: BY COMPLETING THIS PROJECT, WE EXPECT TO HAVE IDENTIFIED DOSING REGIMENS FOR SYSTEMIC [212PB]VMT01 A-RT WITH IMMUNE CHECKPOINT INHIBITORS THAT MAXIMIZE COMPLETE RESPONSES, WHILE MINIMIZING TOXICITIES IN 4 IMMUNE-COMPETENT MOUSE MODELS. WE FURTHER EXPECT TO HAVE DEVELOPED UNDERSTANDING OF THE SYSTEMIC ANTI-TUMOR IMMUNE RESPONSE FOR PRIMARY AND METASTATIC TUMORS THAT CAPTURES KNOWN INTERTUMORAL HETEROGENEITY OF METASTATIC MELANOMA. WE ANTICIPATE THAT THIS WILL LEAD TO CLINICAL TRIALS AND A NEW APPROACH TO METASTATIC MELANOMA PATIENT CARE THAT RESULTS IN MORE COMPLETE RESPONSES AND BETTER QUALITY OF LIFE. $976.7k 6/29/22