Testing a New Radioactive Drug to Treat Melanoma That Has Spread

A Phase 1-1b Study to Evaluate the Safety, Efficacy and Dosimetry of [225Ac]Ac-A9-3408 in Subjects With Unresectable or Metastatic Melanoma

Alpha-9 Oncology USA Inc.PHASE1Recruiting

Check Eligibility Doctor's Note PDF

In Plain English

This trial is testing a new investigational drug called A9-3408 to see if it can safely treat melanoma (including uveal melanoma, the eye cancer form) that has spread to other parts of your body or cannot be surgically removed. The drug works by using a radioactive particle attached to a targeting molecule—think of it like a guided missile that seeks out and destroys cancer cells while minimizing damage to healthy tissue. You would receive this drug as an IV infusion once every 6 weeks, for up to 6 treatments total (about 9 months). Before starting, you'll get a diagnostic scan using a different radioactive tracer to confirm the drug can find your cancer cells. Throughout the trial, you'll have regular doctor visits and tests to check how well the drug is working, monitor for side effects, and measure how much radiation your organs are receiving. This is an early-stage trial (Phase 1-1b), which means researchers are still figuring out the safest and most effective dose. The main goals are to understand what side effects occur, find the highest safe dose, and see if the drug can shrink your tumors—especially if your cancer has stopped responding to other immunotherapy treatments.

What This Trial Does

The goal of this trial is to see if this investigational drug is safe for adult patients with melanoma that has spread to other parts of the body or cannot be removed by surgery. It will also see if this investigational drug can shrink melanoma tumors in the body. The main questions this study aims to answer are: * What are the side effects of this investigational drug? * What is the highest dose of this investigational drug that can be given safely? Participants will: * Take the investigational drug once every 6 weeks, for up to 6 times in total * Visit a doctor's office on a regular basis for checkups and tests

How It Works

This is a multicenter, open-label -1b study of \[225Ac\]Ac-A9-3408 in subjects with or melanoma. The primary aim of the 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 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 or 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.

Who Can Join

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

Age: 18 Years+