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

NCT07076550 | Recruiting Phase 1 DMC

• 1 other identifier: A9-3408-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 4

Brief Summary

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

Conditions

Melanoma Metastatic; Uveal Melanoma, Metastatic; Mucosal Melanoma

Keywords

Metastatic Melanoma; Melanoma; Radiopharmaceuticals; Theranostic

Outcome Measures

Primary Outcomes (2)

• Determine max tolerated dose and recommended Phase 2 Dose

  Rate of DLTs per dose level/cohort

  First 28 days following first study treatment

• Incidence of treatment-related adverse events

  Rate and severity of suspected treatment-related adverse events, change from baseline laboratory values and change from baseline vital signs as graded by CTCAE version 5.0

  From first study treatment until end of treatment

Secondary Outcomes (2)

• Evaluate the preliminary efficacy of [225Ac]Ac-A9-3408 by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)

  Up to 1 year from enrollment

• Evaluate biodistribution and normal organ dosimetry of [225Ac]Ac-A9-3408

  Up to 7 days following each cycle (42 days)

Study Arms (2)

Phase 1 Dose Escalation

EXPERIMENTAL

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.

Drug: [225Ac]Ac-A9-3408; Diagnostic Test: [68Ga]Ga-A9T-3202

Phase 1B Dose Expansion

EXPERIMENTAL

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.

Drug: [225Ac]Ac-A9-3408; Diagnostic Test: [68Ga]Ga-A9T-3202

Interventions

[225Ac]Ac-A9-3408 DRUG

Administered IV

Phase 1 Dose Escalation; Phase 1B Dose Expansion

[68Ga]Ga-A9T-3202 DIAGNOSTIC_TEST

Administered IV

Phase 1 Dose Escalation; Phase 1B Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Alpha-9 Oncology USA Inc.: lead

Study Sites (4)

Alfred Health

Melbourne, Victoria, 3004, Australia

RECRUITING

Austin Health

Melbourne, Victoria, 3084, Australia

RECRUITING

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

NOT YET RECRUITING

GenesisCare Murdoch

Murdoch, Western Australia, 6150, Australia

NOT YET RECRUITING

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis; Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Sam Vohra

CONTACT

+61 300 131 548; sam@avionmedical.com.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2025
• First Posted: July 22, 2025
• Study Start: November 19, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)