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

NCT06881823 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: CAAA802B121012024-516952-17-00
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Prostate Cancer

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; PLND

Outcome Measures

Primary Outcomes (2)

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

  Incidence and severity of dose-limiting toxicities.

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

• 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).

  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)

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

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

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

  at 12 months after surgery

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

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

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

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

• Overall Response Rate (ORR) (Phase l & ll)

  Month 12, Month 15, Month 18

Study Arms (3)

AAA602

ACTIVE COMPARATOR

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

Drug: AAA602; Drug: Gallium (68Ga) gozetotide; Drug: Piflufolastat (18F); Drug: Flotufolastat F 18; Drug: 18F-PSMA-1007

AAA802

ACTIVE COMPARATOR

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

Drug: AAA802; Drug: Gallium (68Ga) gozetotide; Drug: Piflufolastat (18F); Drug: Flotufolastat F 18; Drug: 18F-PSMA-1007

Control Arm

NO INTERVENTION

No neoadjuvant treatment

Interventions

AAA602 DRUG

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

Also known as: Lutetium-177

AAA602

AAA802 DRUG

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

Also known as: Actinium-225

AAA802

Gallium (68Ga) gozetotide DRUG

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

Also known as: Locametz, Illuccix

AAA602; AAA802

Piflufolastat (18F) DRUG

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

Also known as: Pylarify, Pylclari

AAA602; AAA802

Flotufolastat F 18 DRUG

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

Also known as: Posluma

AAA602; AAA802

18F-PSMA-1007 DRUG

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

Also known as: Fluorine-18 PSMA 1007

AAA602; AAA802

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Lutetium-177; Actinium-225; gallium 68 PSMA-11

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: February 25, 2025
• First Posted: March 18, 2025
• Study Start (Estimated): June 29, 2026
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): June 1, 2033
• Last Updated: December 29, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share