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Prostate CancerPhase 1/2NeoPSMANCT06881823

Study to Assess [177Lu]Lu-PSMA-R2 (AAA602) and [225Ac]Ac-PSMA-R2 (AAA802) in Participants With PSMA-positive HRLPC

A Phase 1/2 study testing AAA602, AAA802 and Gallium (68Ga) gozetotide in people with Prostate Cancer, run by Novartis Pharmaceuticals.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this trial is to learn more about the effects of AAA602 and AAA802 in men with prostate-specific membrane antigen (PSMA) positive high-risk localized prostate cancer (HRLPC) before surgery to remove the prostate and lymph nodes present in the pelvis area. Read more about this study

Who is it for?
Ages 18 to 100 years, men only
Conditions the study is for
Prostate Cancer
What is being tested?
AAA602, AAA802 and Gallium (68Ga) gozetotide
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
29 Jun 2026to 1 Jun 2033
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 100 years
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults ≥ 18 years of age.
  • Participants must have PSMA-positive disease as assessed by PSMA PET/CT scan using a PSMA imaging agent as protocol instructed, with eligibility being determined by the sponsor's central reading rules.
  • Histologically confirmed high-risk adenocarcinoma of an intact prostate, and (a) 1 of the following at diagnosis: Gleason score ≥ 8 and/or PSA ≥ 20 nanogram per milliliters (ng/mL), and/or ≥ cT3a or (b) Gleason score 4+3 and PSA ≥ 20 nanogram per milliliters (ng/mL).
  • Adequate organ function:
  • Bone marrow reserve:
  • White blood cell (WBC) count ≥ 3.0 x 109/L and absolute neutrophil count (ANC) ≥ 1.5 x 109/L.
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  • Platelets ≥ 75 x 109/L.
  • Hemoglobin ≥ 8 g/dL
  • Hepatic function:
  • Total bilirubin ≤ 1.5 x the institutional upper limit of normal (ULN). For participants with known Gilbert's Syndrome ≤ 3 x ULN is permitted.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 x ULN
  • Albumin > 3.0 g/dL
  • Renal function:
  • Creatinine clearance ≥ 60 mL/min. Note that participants with findings indicating blockage of urinary outflow are not eligible. No evidence of congenital renal abnormalities with known effect on renal function or voiding abnormalities that may interfere, in the opinion of the principal investigator, with the safe administration of the study treatment.
  • An Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.
  • Indicated to receive radical prostatectomy (RP) and pelvic lymph node dissection (PLND).
  • Sexually active participants with female partners of childbearing potential are eligible to participate if they agree to follow one of the following methods of contraception consistently, starting from screening, during the study and for at least 6 months after the last dose of study treatment:
  • Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent.
  • Are sterilized (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate);
  • Agree to use a male condom and have their partner use a highly effective method of contraception (failure rate < 1% per year) as described in Section 8.4.6 when having penile-vaginal intercourse with a woman of childbearing potential who is not currently pregnant, and who agrees to the use of a condom by her partner.
  • In addition, participants must refrain from donating sperm starting from Screening, during the study and for at least 6 months after the last dose of the study medication.
  • Sexually active participants with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse; or use a male condom during each episode of penile penetration during the study.

Who cannot join

  • Subjects taking prohibited therapies as described in the protocol
  • Any approved or investigational systemic anti-cancer therapy (e.g. chemotherapy, investigational therapy, immunotherapy or biological therapy including monoclonal antibodies) administered for the treatment of HRLPC within 28 days (or 5 times the half-life of that therapy whichever is longer) of the anticipated day C1D1.
  • Previous treatment with any approved or investigational radioligand therapy, approved or investigational radioisotopes.
  • Prior or concurrent radiation therapy of the prostate, other prostate antineoplastic ablative procedures, or hormonal ablation for prostate cancer.
  • Diagnosed with other active malignancies that are expected to alter life expectancy or may interfere with disease assessment. Participants with a prior history of malignancy that has been adequately treated and who have been disease free and treatment free for more than 3 years prior to randomization are eligible, as are participants with adequately treated non-melanoma skin cancer and superficial bladder cancer.
  • Other protocol-defined Inclusion/exclusion may apply.

About this study

Official title: NeoPSMA: A Phase I/II, Open-label, Multi-center Study of Neoadjuvant Treatment With [177Lu]Lu-PSMA-R2 (AAA602) and [225Ac]Ac-PSMA-R2 (AAA802) in Adults With Prostate-specific Membrane Antigen (PSMA) Positive High-risk Localized Prostate Cancer (HRLPC) Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection

The purpose of this trial is to learn more about the effects of AAA602 and AAA802 in men with prostate-specific membrane antigen (PSMA) positive high-risk localized prostate cancer (HRLPC) before surgery to remove the prostate and lymph nodes present in the pelvis area. Lymph nodes are small structures near the prostate that help fight infections. These lymph nodes are removed during surgery because they are a site the disease can spread to.

Read the detailed description

This Phase I/II study is intended to determine the safety, tolerability, anti-tumor activity, pharmacokinetics, and dosimetry of neoadjuvant treatment with the radioligand therapies (RLT) [177Lu]Lu-PSMA-R2 (AAA602) and [225Ac]Ac-PSMA-R2 (AAA802) before surgery, i.e., radical prostatectomy (RP) and pelvic lymph node dissection (PLND), in participants with Prostate-Specific Membrane Antigen (PSMA)-positive high-risk localized prostate cancer (HRLPC).

Study CAAA802B12101 is a Phase I/II open-label, multi-center study investigating AAA602 and AAA802 as neoadjuvant RLTs before surgery in participants with PSMA-positive HRLPC. In Phase I, participants will be assigned to AAA602 or AAA802 dose escalation cohorts to determine the respective maximum tolerated dose (MTD) and/or the recommended dose for Phase II (RP2D). In Phase II, participants will be randomized to one or two investigational arms, i.e., the RP2D of AAA602 or AAA802, or to the control arm. Therefore, Phase II will have two or three treatment arms. In the control arm, participants will be treated with the standard of care (SoC), i.e., they will not receive any neoadjuvant treatment. Supportive care will be allowed.

Following the last dose of completed RLT, participants will complete a post-treatment imaging/Safety follow-up visit. Upon discontinuation of RLT, participants will complete an end of treatment (EOT) visit prior to the post-treatment imaging/Safety follow-up visit.

If participants undergo surgery, the post-treatment imaging/Safety follow-up visit will be performed before undergoing surgery.

After surgery, participants will complete a post-surgery visit and enter the LTFU. No adjuvant treatment is allowed between surgery and biochemical recurrence (BCR).

The investigational treatments in both Phases I and II are neoadjuvant treatment with AAA602 or AAA802 before surgery (RP and PLND). Surgery is to be performed as per the SoC and is not part of the investigational treatment in this study.

The control treatment in Phase II is SoC, i.e., no neoadjuvant treatment.

Conditions
Prostate Cancer
Being tested
AAA602, AAA802, Gallium (68Ga) gozetotide, Piflufolastat (18F), Flotufolastat F 18
Keywords
High Risk Localized Prostate Cancer, prostate-specific membrane antigen, PSMA, neoadjuvant treatment, adults, radioligand therapies, RLT, AAA602, AAA802, Prostate cancer, Phase 1, Phase 2, high-risk localized prostate cancer, HRLPC, Actinium, Lutetium, gozetotide, Radical Prostatectomy, RP, Pelvic Lymph Node Dissection
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AAA602Drug

    Also called Lutetium-177

    [177]Lu-PSMA-R2 Radiopharmaceutical solution for injection/infusion.

  • AAA802Drug

    Also called Actinium-225

    [225]Actinium-PSMA-R2 radiopharmaceutical solution for injection/infusion

  • Gallium (68Ga) gozetotideDrug

    Also called Locametz, Illuccix

    Radioligand Imaging compound. Provided as a kit for radiopharmaceutical preparation of gallium (68Ga) gozetotide. Solution for injection.

  • Piflufolastat (18F)Drug

    Also called Pylarify, Pylclari

    Radioligand Imaging compound. Provided as a ready-to-use radiopharmaceutical.

  • Flotufolastat F 18Drug

    Also called Posluma

    Radioligand Imaging compound. Provided as a ready to use radiopharamceutical.

  • 18F-PSMA-1007Drug

    Also called Fluorine-18 PSMA 1007

    Radioligand Imaging compound. Provided as a ready to use radiopharmaceutical.

Study groups in NCT06881823
Study groupRoleWhat they receive
AAA602Active comparatorAAA602 will be administered as a single intravenous dose. Dose escalation and de-escalation steps will be performed in accordance with the BOIN design.
Receives: Drug: AAA602; Drug: Gallium (68Ga) gozetotide; Drug: Piflufolastat (18F); Drug: Flotufolastat F 18; Drug: 18F-PSMA-1007
AAA802Active comparatorAAA802 will be administered as a single intravenous dose Dose escalation/de-escalation steps will be performed in accordance with the BOIN design.
Receives: Drug: AAA802; Drug: Gallium (68Ga) gozetotide; Drug: Piflufolastat (18F); Drug: Flotufolastat F 18; Drug: 18F-PSMA-1007
Control ArmNo interventionNo neoadjuvant treatment

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with dose-limiting toxicities (DLTs) (Phase l)

    Incidence and severity of dose-limiting toxicities.

    Measured: At the end of cycle 1 (each cycle is maximum 6 weeks)

  2. Biochemical recurrence free survival (BFS) (Phase ll)

    BFS is defined as the time from the date of surgery until the date of confirmed biochemical recurrence (PSA > 0.2 ng/mL on two readings separated by at least 4 weeks measured at least 8 weeks after surgery).

    Measured: From the date of surgery until the date of confirmed biochemical recurrence or death due to any cause, whichever occurs first assessed to approximately 60 months

Secondary outcomes (13)

  1. Biochemical response as measured as Prostate Specific Antigen (PSA)50 (Phase ll)

    PSA50 is defined as the percentage of participants who achieved a ≥ 50% decrease (that is confirmed by a second PSA measurement ≥ 4 weeks later) from baseline at the end of neoadjuvant treatment.

    Measured: From screening until the end of neoadjuvant treatment assessed to approximately 6 months

  2. Overall Response Rate (ORR) at 12 months after surgery (Phase ll)

    ORR is the percentage of participants with a response without addition of any new antineoplastic therapy. Antineoplastic therapy is defined as PSA < 0.2 ng/ml as per central lab at month 12 (that is confirmed by a second PSA measurement ≥ 4 weeks later).

    Measured: at 12 months after surgery

  3. Change from baseline in domain scores of the EPIC-26 (Phase ll)

    EPIC-26 (expanded prostate cancer index composite) is a health related quality of life assessment. It contains five symptom domains (urinary incontinence, urinary irritative/obstructive, sexual, bowel, hormonal), scored from 0 (worst) to 100 (best), that can be tracked over time to understand symptom burden and functional outcomes.

    Measured: From screening to end of long term follow up assessed up to approximately 66 months

  4. Change from baseline on FACT-GP5 item (Phase ll)

    FACT-GP5 (Functional assessment of Cancer Therapy item-GP5) is a health related assessment measuring the overall impact of treatment toxicity. The assessment consists of 1 question - 'I am bothered by side effects of treatment'. The scoring range goes from 0 (not at all) to 4 (very much).

    Measured: From screening to end of long term follow up assessed up to approximately 66 months

  5. Overall Response Rate (ORR) (Phase l & ll)

    ORR is the percentage of participants with a complete biochemical response without addition of any new antineoplastic therapy other than the study medication (AAA602/AAA802 and/or Radical Prostatectomy (RP) and Pelvic Lymph Node Dissection (PLND)). Antineoplastic therapy is defined as PSA < 0.2 ng/ml as per central lab (that is confirmed by a second PSA measurement ≥ 4 weeks later).

    Measured: Month 12, Month 15, Month 18

  6. Percentage of participants with a functional response on PSMA PET/CT

    Functional response is defined as either complete PSMA response if all PSMA-avid lesions had resolved, a partial response if there was >30% decrease in SUVmax, progressive disease if there was >30% increase in SUVmax, or the presence of new PSMA-avid lesions and stable disease if the response did not meet the criteria for complete, partial, or progressive PSMA-avid disease. The response will be assessed at the end of neoadjuvant treatment with radioligand therapy compared to baseline (Eapen et al 2024).

    Measured: From screening until the end of neoadjuvant treatment assessed to approximately 6 months

  7. Percentage of participants achieving pathological complete response (absence of disease) or minimal residual disease (Phase l & ll)

    Percentage of participants achieving pathological complete response (absence of disease) or minimal residual disease (Ph I \& II) as assessed by local review and independent central review.

    Measured: From screening until post-surgery follow up assessed at approximately 7.5 months

  8. Concordance in the evaluation of pathological response between local review and independent central review (Phase l & ll)

    Correspondence between local and independent central assessment of participants achieving pathological complete response (absence of disease) or minimal residual disease.

    Measured: From screening until post-surgery follow up assessed at approximately 7.5 months

  9. Radiation absorbed doses in organs and tumors of AAA602 (Phase l & ll)

    To evaluate tumor and organs dosimetry of AAA602.

    Measured: From cycle 1 day 1 until until approximately cycle 2 day 3 (cycle is maximum 6 weeks)

  10. Time concentration profiles and Pharmacokinetics parameters of AAA802 and AAA602

    Time-concentration profiles and PK parameters of AAA602 and AAA802 (e.g. AUC, Cmax).

    Measured: From cycle 1 day 1 until until approximately cycle 1 day 3 (cycle is maximum 6 weeks)

  11. Percentage of participants with surgical complications graded according to the Clavien-Dindo classification (Phase l & ll)To evaluate surgical safety (phase l & ll)

    Number and severity of complications based on the Clavien-Dindo classification (assessment performed post surgery). The Clavien Dindo Classification is used to rank the severity of a surgical complication. It is based on the type of therapy needed to correct the complication. The scale consists of several grades (Grade I, II, IIIa, IIIb, IVa, IVb and V). Grade I complications being the mildest and V being most significant.

    Measured: From screening until post-surgery follow up assessed at approximately 7.5 months

  12. Percentage of participants achieving a complete response to therapy (Phase l & ll)

    Percentage of participants achieving undetectable PSA and absence of disease on PSMA PET/CT during neoadjuvant treatment. Complete response to safety is defined as: PSA < 0.1 ng/ml that is confirmed by a second PSA measurement ≥ 4 weeks later; the absence of any PSMA uptake on PSMA PET/CT.

    Measured: From screening until end cycle 2 assessed up to 20 weeks (cycle is maximum 6 weeks)

  13. Percentage of participants achieving PSA < 0.2 (Phase l & ll)

    Percentage of participants achieving undetectable PSA (<0.2) after treatment with AAA802 and AAA602 post biochemical recurrence. PSA < 0.2 is confirmed by a second PSA measurement ≥ 4 weeks later in response to treatment with cycles of AAA602 and/or AAA802 administered following biochemical recurrence after surgery;

    Measured: From cycle 1 day 1 of post progression treatment to approximately 60 months after surgery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Mar 2025
  2. Study start29 Jun 2026 (estimated)
  3. Primary completion31 Mar 2030 (estimated)
  4. Study completion1 Jun 2033 (estimated)

Why it stopped: The radioligands to be evaluated showed acceptable safety but limited benefit in metastatic prostate cancer

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06881823
Sponsor's protocol ID
CAAA802B12101
Other IDs
2024-516952-17-00
Acronym
NeoPSMA
Status last verified
Dec 2025
First submitted
25 Feb 2025
Last updated
29 Dec 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AAA602, AAA802 and Gallium (68Ga) gozetotide in people with Prostate Cancer, run by Novartis Pharmaceuticals.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 29 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with dose-limiting toxicities (DLTs) (Phase l) (time frame: At the end of cycle 1 (each cycle is maximum 6 weeks)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06881823.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2025.

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