Open-label Study Comparing AAA817 Versus Standard of Care in the Treatment of Previously Treated PSMA-positive mCRPC Adults Who Have Disease Progressed on or After [177Lu]Lu-PSMA Targeted Therapy

NCT06780670 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: CAAA817A122012024-512342-42-00
• Study Type: interventional
• Target: 443
• Locations: 12 countries
• Sites: 72

Brief Summary

This is a Phase II/III study. Patient population is adult participants with PSMA-positive mCRPC who had treatments with androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. Treatment of interest: the investigational treatment is AAA817 regardless of subsequent anti-neoplastic treatment. The control treatment is investigator's choice of Standard of Care, regardless of subsequent anti-neoplastic treatment

Conditions

Prostate Cancer

Keywords

post [177Lu]Lu-PSMA targeted therapy; PSMA-positive; mCRPC adults; Metastatic castration-resistant prostate cancer; AAA817; [225Ac]Ac-PSMA-617; PSMA-based targeted therapy; Standard of Care; SOC

Outcome Measures

Primary Outcomes (5)

• Biochemical response rate (Phase II)

  Biochemical response rate as defined as the percentage of participants who achieved a ≥ 50% decrease from baseline that is confirmed by a second measurement

  from date of randomization up to approximately 24 months

• Adverse Events (AEs) and Serious Adverse Events (SAEs), and deaths - Phase II

  Safety defined as the type, incidence and severity of AEs and SAEs, and deaths

  from day of randomization to 30 days after End of Treatment or (last AAA817 dose date + 55 days, last dose date of SoC + 30 days), whichever is later

• Tolerability of the proposed dose of AAA817- Phase II

  Percentage of participants who experienced Dose interruptions, reductions, discontinuation, dose intensity and duration of exposure

  From on-treatment period which start from the first dose of study treatment until 30 days post-last dose date for SoC and 55 days post last-dose for AAA817

• Radiographic progression-free survival (rPFS)- Phase III

  Percentage of participants who are alive without radiographic progression or who are lost to follow-up at the time of analysis

  from date of randomization up to approximately 24 months

• Overall survival (OS)- Phase III

  Percentage of participants who are alive or who are lost to follow-up at the time of analysis

  from date of randomization up to approximately 24 months

Secondary Outcomes (14)

• Radiographic progression-free survival (rPFS)- Phase II

  from date of randomization up to approximately 24 months

• Progression free survival (PFS)- Phase II

  from date of randomization up to approximately 24 months

• Overall response rate (ORR)- Phase II

  from date of randomization up to approximately 24 months

• Disease control rate (DCR)- Phase II

  from date of randomization up to approximately 24 months

• Overall survival (OS)- Phase II

  from date of randomization up to approximately 24 months

Study Arms (4)

Phase II: AAA817 Dose B

EXPERIMENTAL

AAA817 will be given for a number of cycles; a cycle = 8 weeks

Drug: AAA817

Phase III: Investigator's choice of SoC

ACTIVE COMPARATOR

Participants will be given Standard of Care (SOC) treatment per Investigator's choice.

Drug: Investigators choice of SoC

Phase II: AAA817 Dose A

EXPERIMENTAL

AAA817 Dose A will be given for a number of cycles: a cycle = 8 weeks

Drug: AAA817

Phase III: Recommended Phase 3 Dose of AAA817

EXPERIMENTAL

Rp3D of AAA817 will be given for a number of cycles; a cycle = 8 weeks

Drug: AAA817

Interventions

Investigators choice of SoC DRUG

The control treatment in Phase III is investigator's choice of SoC

Phase III: Investigator's choice of SoC

AAA817 DRUG

The investigational treatment is AAA817

Also known as: [225Ac]Ac-PSMA-617)

Phase II: AAA817 Dose A

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.
• ECOG performance status of 0 to 2.
• histopathological and/or cytological confirmation of adenocarcinoma of the prostate.
• PSMA-positive disease as assessed by PSMA PET/CT scan using an approved PSMA imaging agent as protocol instructed,
• castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L).
• Prior treatments with an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy.
• ≥ 1 metastatic lesion that is present on screening/baseline CT, MRI, or bone scan imaging obtained ≤ 28 days prior to randomization
• eGFR as requested by the sponsor

You may not qualify if:

• Any investigational agents within 28 days prior to the day of randomization.
• Any 225Ac-based investigational compound used prior to the day of randomization.
• Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity.
• Concurrent acute kidney injury (renal failure developed between 48 hours to 7 days) or chronic kidney disease (at least 3 months of ongoing renal injury)
• Baseline xerostomia ≥ Grade 2 by CTCAE v.5
• History of uncontrolled hypertension, myocardial infarction (MI), angina pectoris, or coronary artery bypass graft (CABG) within 6 months prior to ICF signature and/or clinically active significant cardiac disease
• History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system within the past 5 years (except for basal cell carcinoma or actinic keratosis that have been treated with no evidence of recurrence in the past 3 months, non-invasive malignant colon polyps that have been removed).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (72)

VA Greater LA Healthcare System

Los Angeles, California, 90073, United States

RECRUITING

Stanford University Medical Center

Palo Alto, California, 94304, United States

RECRUITING

Sansum Clinic

Santa Barbara, California, 93105, United States

RECRUITING

Saint Johns Cancer Institute

Santa Monica, California, 90404, United States

RECRUITING

Hartford Hospital

Hartford, Connecticut, 06102, United States

RECRUITING

AdventHealth

Orlando, Florida, 32804, United States

RECRUITING

University Cancer and Blood Center LLC

Athens, Georgia, 30607, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

WA Uni School Of Med

St Louis, Missouri, 63110, United States

RECRUITING

Nebraska Cancer Specialists

Omaha, Nebraska, 68154, United States

RECRUITING

New Jersey Urology LLC

Voorhees Township, New Jersey, 08043, United States

RECRUITING

Associated Med Professionals of NY

Syracuse, New York, 13210, United States

RECRUITING

Montefiore Medical Center

The Bronx, New York, 10467, United States

RECRUITING

Central Ohio Urology Group

Gahanna, Ohio, 43230, United States

RECRUITING

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

RECRUITING

Texas Oncology

Dallas, Texas, 75251, United States

RECRUITING

Urology San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Utah Intermountain Medical Center

Murray, Utah, 84107, United States

RECRUITING

Medical College Of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Novartis Investigative Site

Darlinghurst, New South Wales, 2010, Australia

RECRUITING

Novartis Investigative Site

Herston, Queensland, 4029, Australia

RECRUITING

Novartis Investigative Site

Melbourne, Victoria, 3004, Australia

RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, 01308-050, Brazil

RECRUITING

Novartis Investigative Site

São Paulo, São Paulo, 05652-000, Brazil

RECRUITING

Novartis Investigative Site

Fuzhou, Fujian, 350025, China

RECRUITING

Novartis Investigative Site

Wuhan, Hubei, 430022, China

RECRUITING

Novartis Investigative Site

Wuhan, Hubei, 430030, China

RECRUITING

Novartis Investigative Site

Nanjing, Jiangsu, 210006, China

RECRUITING

Novartis Investigative Site

Nanjing, Jiangsu, 210029, China

RECRUITING

Novartis Investigative Site

Shenyang, Liaoning, 110011, China

RECRUITING

Novartis Investigative Site

Xian, Shanxi, 710032, China

RECRUITING

Novartis Investigative Site

Xian, Shanxi, 710061, China

RECRUITING

Novartis Investigative Site

Chengdu, Sichuan, 610041, China

RECRUITING

Novartis Investigative Site

Beijing, 100034, China

RECRUITING

Novartis Investigative Site

Beijing, 100036, China

RECRUITING

Novartis Investigative Site

Guangzhou, 510060, China

RECRUITING

Novartis Investigative Site

Shanghai, 200025, China

RECRUITING

Novartis Investigative Site

Shanghai, 200032, China

RECRUITING

Novartis Investigative Site

Tianjin, 300300, China

RECRUITING

Novartis Investigative Site

Hong Kong, 999077, Hong Kong

RECRUITING

Novartis Investigative Site

Beersheba, 8457108, Israel

RECRUITING

Novartis Investigative Site

Haifa, 3109601, Israel

RECRUITING

Novartis Investigative Site

Petah Tikva, 4941492, Israel

RECRUITING

Novartis Investigative Site

Ramat Gan, 5265601, Israel

RECRUITING

Novartis Investigative Site

Tel Aviv, 6423906, Israel

RECRUITING

Novartis Investigative Site

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Novartis Investigative Site

Sapporo, Hokkaido, 060-8648, Japan

RECRUITING

Novartis Investigative Site

Kobe, Hyōgo, 6500047, Japan

RECRUITING

Novartis Investigative Site

Yokohama, Kanagawa, 236-0004, Japan

RECRUITING

Novartis Investigative Site

Chiba, 260-8717, Japan

RECRUITING

Novartis Investigative Site

Fukuoka, 812-0033, Japan

RECRUITING

Novartis Investigative Site

Fukuoka, 8128582, Japan

RECRUITING

Novartis Investigative Site

Fukushima, 9601295, Japan

RECRUITING

Novartis Investigative Site

Ishikawa, 9208641, Japan

RECRUITING

Novartis Investigative Site

Kyoto, 6068507, Japan

RECRUITING

Novartis Investigative Site

Petaling Jaya, Selangor, 46050, Malaysia

RECRUITING

Novartis Investigative Site

Singapore, 119228, Singapore

RECRUITING

Novartis Investigative Site

Singapore, 168583, Singapore

RECRUITING

Novartis Investigative Site

Singapore, 258499, Singapore

RECRUITING

Novartis Investigative Site

Seoul, 03080, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 03722, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 05505, South Korea

RECRUITING

Novartis Investigative Site

Seoul, 06591, South Korea

RECRUITING

Novartis Investigative Site

Basel, 4031, Switzerland

RECRUITING

Novartis Investigative Site

Bern, 3010, Switzerland

RECRUITING

Novartis Investigative Site

Taipei, 10002, Taiwan

RECRUITING

Novartis Investigative Site

Taipei, 103616, Taiwan

RECRUITING

Novartis Investigative Site

Taipei, 11217, Taiwan

RECRUITING

Novartis Investigative Site

Taoyuan, 33305, Taiwan

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

(225)Ac-PSMA-617

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: January 17, 2025
• Study Start: February 27, 2025
• Primary Completion (Estimated): June 27, 2028
• Study Completion (Estimated): July 19, 2033
• Last Updated: April 30, 2026

Record last verified: 2026-04

Locations

CH (2); HK (1); MY (1); BR (2); AU (3); CN (15); KR (4); JP (10); IL (5); US (22); TW (4); SG (3)