# Combining receptor-targeted alpha particle therapy and immunotherapy to achieve complete responses in metastatic melanoma

> **NIH NIH R44** · VIEWPOINT MOLECULAR TARGETING, INC. · 2022 · $976,668

## Abstract

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 <30%).
Radiopharmaceutical therapies are emerging as an exciting alternative in oncology and systemic receptor-
targeted alpha-particle therapy (a-RT) is emerging as particularly transformative due to recent reports of
complete responses in early trials. Viewpoint is introducing an MC1R-targeted peptide-based a-RT
([212Pb]VMT01) for Stage III/IV metastatic melanoma and has received IND approval (#152145) to begin
[203Pb]VMT01 imaging trials (Mayo Clinic) to prepare for [212Pb]VMT01 monotherapy trials. However, our now
published predicate R&D (PMID 34359580) revealed a combination of [212Pb]VMT01 a-RT and immunotherapy
(ICI) that achieved a 43% complete response rate in an immune-competent mouse melanoma model and a
tumor-specific immune response to [212Pb]VMT01. This is significant because this model is unresponsive to ICI
alone, which suggests that combining ICIs with a-RT could improve outcomes for thousands of melanoma
patients who are unresponsive to current standard of care treatment with single or dual agent ICI blockade. Thus,
there is a rigorous scientific basis to develop combined ICI therapy and [212Pb]VMT01 for metastatic melanoma.
PHASE I MILESTONES: >$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 α-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 clinica...

## Key facts

- **NIH application ID:** 10482495
- **Project number:** 2R44CA232954-02A1
- **Recipient organization:** VIEWPOINT MOLECULAR TARGETING, INC.
- **Principal Investigator:** Michael King Schultz
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $976,668
- **Award type:** 2
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10482495

## Citation

> US National Institutes of Health, RePORTER application 10482495, Combining receptor-targeted alpha particle therapy and immunotherapy to achieve complete responses in metastatic melanoma (2R44CA232954-02A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10482495. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*