Clinical Trial Finder

Inclusion Criteria:

• - Able to provide written informed consent.

• - [68Ga]Ga-A9T-3202 uptake in at least one measurable lesion (per RECIST v1.1) on PET scan.

• - Histologically or cytologically confirmed unresectable or metastatic melanoma with disease progression on prior standard of care therapy.

• - Adequate ECOG performance status.

• - Adequate baseline organ function within 14 days of first dose of investigational product.

• - Recovered from side effects of prior anticancer therapy.

• - Women of childbearing potential (WOCBP) must have a negative pregnancy test and follow adequate birth control method(s) during the treatment period and for at least 6 months after last dose of [225Ac]Ac-A9-3408.

Sexually active males with partners who are WOCBP must agree to adequate birth control method(s) during the treatment period and for at least 3 months after last dose of [225Ac]Ac-A9-3408.

Exclusion Criteria:

• - Previous treatment with radioactive nuclides except radioactive imaging tracers.

• - Treatment with another investigational product shortly prior to first dose of [225Ac]Ac-A9-3408 with exception of anti-PD-1/PD-L1 agents.

• - Concurrent anticancer therapy.

• - Major surgery within 4 weeks of first dose of investigational product.

• - Second malignancy within 2 years.

• - Active, clinically serious infection.

• - Known infusion reactions to components of the investigational product.

• - Other clinically serious health conditions including cardiovascular and or severe infectious diseases.

• - Significant central nervous system metastatic disease.

- Pregnant, breastfeeding or unwilling to practice adequate birth control method(s) - Any condition per the opinion of the investigator that would impact the safety of the subject, protocol adherence or ability to provide informed consent

This is a multicenter, open-label Phase 1-1b study of [225Ac]Ac-A9-3408 in subjects with unresectable or metastatic melanoma. The primary aim of the Phase 1 portion of the study is to evaluate the safety and tolerability as well as the normal organ and tumor dosimetry of [225Ac]Ac-A9-3408 and to select a recommended Phase 2 dose (RP2D). The aim of Phase 1b will be to evaluate the safety, efficacy, and normal organ and tumor dosimetry of [225Ac]Ac-A9-3408 administered at the RP2D in subjects with unresectable or metastatic cutaneous melanoma who had confirmed disease progression while receiving an anti-PD-1/PD-L1-containing regimen. The interventional diagnostic [68Ga]Ga-A9T-3202 will be administered intravenously (IV) once during screening. The interventional drug [225Ac]Ac-A9-3408 will be administered intravenously (IV) once every 6 weeks, for a total of up to 6 cycles.

Arms

Experimental: Phase 1 Dose Escalation

Participants enrolled in Dose Escalation will receive a single dose of the investigational diagnostic agent [68Ga]Ga-A9T-3202 during screening, and receive the investigational treatment [225Ac]Ac-A9-3408 once every 6 weeks, for up to 6 total cycles.

Experimental: Phase 1B Dose Expansion

Participants enrolled in Dose Expansion will receive a single dose of the investigational diagnostic agent [68Ga]Ga-A9T-3202 during screening, and receive the investigational treatment [225Ac]Ac-A9-3408 once every 6 weeks, for up to 6 total cycles.

Interventions

Drug: - [225Ac]Ac-A9-3408

Administered IV

Diagnostic Test: - [68Ga]Ga-A9T-3202

Administered IV