A Phase 1-1b Study to Evaluate the Safety, Efficacy and Dosimetry of Study Drug A9-3408 in Subjects With Metastatic Melanoma

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.

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