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

NCT ID: NCT06881823

Last Updated: 2025-12-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1/PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2026-06-29

Study Completion Date

2033-06-01

Brief Summary

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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.

Detailed Description

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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

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Prostate Cancer

Keywords

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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 PLND

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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AAA602

AAA602 will be administered as a single intravenous dose. Dose escalation and de-escalation steps will be performed in accordance with the BOIN design.

Group Type ACTIVE_COMPARATOR

AAA602

Intervention Type DRUG

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

Gallium (68Ga) gozetotide

Intervention Type DRUG

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

Piflufolastat (18F)

Intervention Type DRUG

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

Flotufolastat F 18

Intervention Type DRUG

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

18F-PSMA-1007

Intervention Type DRUG

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

AAA802

AAA802 will be administered as a single intravenous dose Dose escalation/de-escalation steps will be performed in accordance with the BOIN design.

Group Type ACTIVE_COMPARATOR

AAA802

Intervention Type DRUG

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

Gallium (68Ga) gozetotide

Intervention Type DRUG

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

Piflufolastat (18F)

Intervention Type DRUG

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

Flotufolastat F 18

Intervention Type DRUG

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

18F-PSMA-1007

Intervention Type DRUG

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

Control Arm

No neoadjuvant treatment

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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AAA602

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

Intervention Type DRUG

AAA802

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

Intervention Type DRUG

Gallium (68Ga) gozetotide

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

Intervention Type DRUG

Piflufolastat (18F)

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

Intervention Type DRUG

Flotufolastat F 18

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

Intervention Type DRUG

18F-PSMA-1007

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

Intervention Type DRUG

Other Intervention Names

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Lutetium-177 Actinium-225 Locametz Illuccix Pylarify Pylclari Posluma Fluorine-18 PSMA 1007

Eligibility Criteria

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Inclusion Criteria

* 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.
* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Other Identifiers

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2024-516952-17-00

Identifier Type: OTHER

Identifier Source: secondary_id

CAAA802B12101

Identifier Type: -

Identifier Source: org_study_id