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
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
50
Administered IV
Administered IV
Alfred Health
Melbourne, Victoria, Australia
RECRUITINGFiona Stanley Hospital
Murdoch, Western Australia, Australia
NOT_YET_RECRUITINGGenesisCare Murdoch
Murdoch, Western Australia, Australia
NOT_YET_RECRUITINGDetermine max tolerated dose and recommended Phase 2 Dose
Rate of DLTs per dose level/cohort
Time frame: 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
Time frame: From first study treatment until end of treatment
Evaluate the preliminary efficacy of [225Ac]Ac-A9-3408 by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Percent of patients who achieve an overall response (ORR), defined as the percent of patients who achieve a complete response (CR) or partial response (PR) by RECIST v1.1
Time frame: Up to 1 year from enrollment
Evaluate biodistribution and normal organ dosimetry of [225Ac]Ac-A9-3408
Absorbed radiation dose estimates (Gy) in normal organs for \[225Ac\]Ac-A9-3408
Time frame: Up to 7 days following each cycle (42 days)
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