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225Ac-PSMA-R2

Phase 1

Prostate Cancer | Small molecule | Oncology |Novartis AG|Last Updated: Aug 19, 2026

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment33

FDA Designations

No designations recorded

Clinical trial landscape

225Ac-PSMA-R2 · 1 trial · 1 indication

Phase 1 1
NCT05983198Phase I/II Study of [225Ac]Ac-PSMA-R2 in PSMA-positive Prostate Cancer, With/Without Prior 177Lu-PSMA RLTProstate Cancer
ACTIVE NOT_RECRUITING33 Analytics
PHASE1ACTIVE NOT_RECRUITING
Phase I/II Study of [225Ac]Ac-PSMA-R2 in PSMA-positive Prostate Cancer, With/Without Prior 177Lu-PSMA RLT
Prostate CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Phase I Dose Escalation: Incidence and severity of DLTs during the DLT observation period
Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration

To determine the Recommended Dose for Expansion (RDE) and corresponding regimen for 225Ac-PSMA-R2 monotherapy in PSMA-positive in: * Group-1 (mCRPC): Participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu). * Group-2 (mCRPC): Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu). * Group-3 (mHSPC): Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).

Phase I Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by group and frequency schedule
From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months

The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

Phase I Dose Escalation: Tolerability
Up to 6 weeks after the first 225AC-PSMA-R2 dose administration

Frequency of dose interruptions, reductions, discontinuations, and dose intensity by group.

Phase ll Dose Expansion: Overall Response Rate (ORR)
From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months

Overall Response Rate (ORR) is defined as the proportion of participants with confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue according to Prostate Cancer Working Group 3 (PCWG3) -modified RECIST v1.1 in absence of bone progression (as per PCWG3).

Secondary Endpoints

Phase I Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs)
Up to 6 months after the last 225Ac-PSMA-R2 dose administration
Phase ll: Dose Expansion: Incidence and severity of AEs and serious adverse events (SAEs)
Assessed up to approximately 15 months.
Phase I Dose Escalation & Dose Expansion: Frequency of dose interruptions, reductions, discontinuations, and dose intensity by treatment.
At day 1 of each cycle (1 cycle = up to 6 weeks)
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Group-1 (mCRPC/ post-177Lu)EXPERIMENTAL1. Dose Escalation: All eligible participants with Metastatic Castration Resistant Prostate Cancer (mCRPC) who have received anti-cancer treatment (post-Androgen Receptor Pathway Inhibitors (ARPI), post-taxane based chemotherapy and heavily pre-treated and having already received prior 177Lu-labelled Prostate Specific Membrane Antigen (PSMA)-targeting Radioligand Therapy (RLT) will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 1. 2. Dose Expansion: Once RDE is determined for Group 1, participants who have previously received 177Lu-PSMA-RLT will be enrolled in Group 1 dose expansion.
Group-2 (mCRPC/ pre-177Lu)EXPERIMENTAL1. Dose Escalation: All eligible participants with mCRPC who have received anti-cancer treatment (post-Androgen Receptor Pathway Inhibitors (ARPI), prior taxane-based chemotherapy is not required, but have never been treated with 177Lu-labelled PSMA-targeted RLT (177Lu-labelled PSMA-targeted RLT treatment naïve) will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 2. 2. Dose Expansion: Once RDE is determined for Group 2, participants naïve to 177Lu-labelled PSMA-targeted Radioligand Therapy (RLT) will be enrolled in Group 2 dose expansion.
Group 3 (mHSPC/ pre-177Lu)EXPERIMENTAL1. Dose Escalation: All eligible participants with mHSPC (177Lu-labelled PSMA-targeted RLT treatment naïve), who are treatment naive or minimally treated with a) luteinizing hormone-releasing hormone (LHRH) agonist/antagonists or bilateral orchiectomy with or without first generation antiandrogen (e.g. bicalutamide, flutamide) b) CYP17 inhibitor or ARDT exposure. Patient in this group will start treatment with 225Ac-PSMA-R2 after group 1 and group 2 patients. 2. Dose Expansion: Once RDE is determined for Group 3, participants will be enrolled in Group 3 dose expansion.

Interventions

NameTypeDescription
225Ac-PSMA-R2DRUGPSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
68Ga-PSMA-R2RADIATIONKit for radiopharmaceutical preparation
68Ga-PSMA-11RADIATIONKit for radiopharmaceutical preparation
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Eligibility Criteria

Age Range18 Years to 100 Years
SexMALE
Healthy VolunteersNo
Study Sites9

Key Inclusion Criteria: * Evidence of PSMA-positive disease by 68Ga-PSMA-11 PET/CT and eligible as determined by central reading * Documented progressive mCRPC or mHSPC * Adequate organ function * Prior orchiectomy or ongoing ADT and should have received prior 177Lu-PSMA-RLT (Group1 dose escalation...

Countries:United StatesAustraliaCanadaFrance
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Competitive Landscape -Prostate Cancer 254 trials

Recent Changes (Last 90 Days)

LOWAug 20, 2026NCT05983198lastUpdatePostDate: changed
LOWAug 20, 2026NCT05983198lastUpdatePostDate: changed
LOWAug 20, 2026NCT05983198lastUpdatePostDate: changed
LOWAug 20, 2026NCT05983198lastUpdatePostDate: changed
MEDIUMJun 29, 2026NCT05983198primaryCompletionDate: changed
MEDIUMJun 29, 2026NCT05983198primaryCompletionDate: changed

Frequently asked questions about 225Ac-PSMA-R2

What is 225Ac-PSMA-R2 used for?

225Ac-PSMA-R2 is an investigational small molecule being developed for the treatment of prostate cancer. It is currently in Phase 1 clinical development and is being studied in patients with PSMA-positive prostate cancer, including those who have or have not received prior 177Lu-PSMA radioligand therapy.

What does 225Ac-PSMA-R2 target?

225Ac-PSMA-R2 targets PSMA, or prostate-specific membrane antigen, a protein that is highly expressed on prostate cancer cells. By binding to PSMA, the drug delivers the radioactive isotope actinium-225 directly to the tumor cells, which is intended to damage and kill them.

Who makes 225Ac-PSMA-R2?

225Ac-PSMA-R2 is being developed by Novartis AG, a global healthcare company. Novartis is listed on the stock exchange under the ticker symbol NVS.

What phase is 225Ac-PSMA-R2 in?

225Ac-PSMA-R2 is currently in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. The ongoing trial is a Phase I/II study, but the drug is still in the early stages of clinical testing.

What clinical trials is 225Ac-PSMA-R2 in?

225Ac-PSMA-R2 is being evaluated in a Phase I/II study with the identifier NCT05983198. This trial is active but not recruiting participants and has an enrollment of 33 patients. The study is being conducted in the United States, Australia, Canada, and France.

Is 225Ac-PSMA-R2 the same as [225Ac]Ac-PSMA-R2?

Yes, 225Ac-PSMA-R2 and [225Ac]Ac-PSMA-R2 refer to the same investigational drug. The clinical trial NCT05983198 uses the name [225Ac]Ac-PSMA-R2 to describe the study treatment for PSMA-positive prostate cancer.