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NCT06780670PHASE2, PHASE3Recruiting

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

Novartis Pharmaceuticals

Start Date

2/27/2025

Completion Date

7/19/2033

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

Detailed Description

Study CAAA817A12201 consists of 2 parts: a randomized, open-label, international, multicenter, phase II study (Phase II) to collect more information to support the proposed dose of AAA817 and a randomized, open-label, international, multicenter, 2- arm phase III study (Phase III) aimed to evaluate the efficacy and safety of proposed dose of AAA817 vs. investigator's choice of standard of care (SoC) in the treatment of adult participants with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who had treatments with ARPI and taxane-based chemotherapy, and progressed on or after \[177Lu\]Lu-PSMA targeted therapy. The purpose of the phase II part (Phase II) of this study is to collect additional information to support proposed phase III dose of AAA817.

Eligibility Criteria

Age Range: 18 years to 100 years

Inclusion Criteria: ∙ * 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 Exclusion Criteria: * 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). Other protocol-defined inclusion/exclusion criteria may apply.

Interventions

DRUG

Investigators choice of SoC

DRUG

AAA817

DRUG

AAA817

DRUG

AAA817

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Conditions

Prostate Cancer

Locations

VA Greater LA Healthcare System

Los Angeles, California 90073

United States

VA Palo Alto Health Care System

Palo Alto, California 94304-1207

United States

Stanford University Medical Center

Palo Alto, California 94304

United States

Sansum Clinic

Santa Barbara, California 93105

United States

Saint Johns Cancer Institute

Santa Monica, California 90404

United States

Hartford Hospital

Hartford, Connecticut 06102

United States

AdventHealth

Orlando, Florida 32804

United States

University Cancer and Blood Center LLC

Athens, Georgia 30607

United States

Emory University

Atlanta, Georgia 30322

United States

Indiana University

Indianapolis, Indiana 46202

United States

University of Kansas Hospital

Kansas City, Kansas 66160

United States

East Jefferson Hospital

Metairie, Louisiana 70006

United States

Dana Farber Cancer Institute

Boston, Massachusetts 02115

United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts 02215

United States

WA Uni School Of Med

St Louis, Missouri 63110

United States

Nebraska Cancer Specialists

Omaha, Nebraska 68154

United States

New Jersey Urology LLC

Voorhees Township, New Jersey 08043

United States

Associated Med Professionals of NY

Syracuse, New York 13210

United States

Montefiore Medical Center

The Bronx, New York 10467

United States

Central Ohio Urology Group

Gahanna, Ohio 43230

United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania 19111

United States

Carolina Urologic Research Center

Myrtle Beach, South Carolina 29572

United States

Texas Oncology

Dallas, Texas 75251

United States

Urology San Antonio

San Antonio, Texas 78229

United States

Utah Intermountain Medical Center

Murray, Utah 84107

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington 98109-1024

United States

Medical College Of Wisconsin

Milwaukee, Wisconsin 53226

United States

Novartis Investigative Site

Darlinghurst, New South Wales 2010

Australia

Novartis Investigative Site

Herston, Queensland 4029

Australia

Novartis Investigative Site

Melbourne, Victoria 3004

Australia

Novartis Investigative Site

São Paulo, São Paulo 01308-050

Brazil

Novartis Investigative Site

São Paulo, São Paulo 05652-000

Brazil

Novartis Investigative Site

Fuzhou, Fujian 350025

China

Novartis Investigative Site

Wuhan, Hubei 430022

China

Novartis Investigative Site

Wuhan, Hubei 430030

China

Novartis Investigative Site

Nanjing, Jiangsu 210006

China

Novartis Investigative Site

Nanjing, Jiangsu 210029

China

Novartis Investigative Site

Shenyang, Liaoning 110011

China

Novartis Investigative Site

Xian, Shanxi 710032

China

Novartis Investigative Site

Xian, Shanxi 710061

China

Novartis Investigative Site

Chengdu, Sichuan 610041

China

Novartis Investigative Site

Beijing, 100034

China

Novartis Investigative Site

Beijing, 100036

China

Novartis Investigative Site

Guangzhou, 510060

China

Novartis Investigative Site

Shanghai, 200025

China

Novartis Investigative Site

Shanghai, 200032

China

Novartis Investigative Site

Tianjin, 300300

China

Novartis Investigative Site

Hong Kong, 999077

Hong Kong

Novartis Investigative Site

Beersheba, 8457108

Israel

Novartis Investigative Site

Haifa, 3109601

Israel

Novartis Investigative Site

Jerusalem, 9112001

Israel

Novartis Investigative Site

Petah Tikva, 4941492

Israel

Novartis Investigative Site

Ramat Gan, 5265601

Israel

Novartis Investigative Site

Tel Aviv, 6423906

Israel

Novartis Investigative Site

Kashiwa, Chiba 277-8577

Japan

Novartis Investigative Site

Sapporo, Hokkaido 060-8648

Japan

Novartis Investigative Site

Kobe, Hyōgo 6500047

Japan

Novartis Investigative Site

Yokohama, Kanagawa 236-0004

Japan

Novartis Investigative Site

Chiba, 260-8717

Japan

Novartis Investigative Site

Fukuoka, 811-0213

Japan

Novartis Investigative Site

Fukuoka, 812-0033

Japan

Novartis Investigative Site

Fukuoka, 8128582

Japan

Novartis Investigative Site

Fukushima, 9601295

Japan

Novartis Investigative Site

Ishikawa, 9208641

Japan

Novartis Investigative Site

Kyoto, 6068507

Japan

Novartis Investigative Site

Petaling Jaya, Selangor 46050

Malaysia

Novartis Investigative Site

Petaling Jaya, Selangor 46150

Malaysia

Novartis Investigative Site

Singapore, 119228

Singapore

Novartis Investigative Site

Singapore, 168583

Singapore

Novartis Investigative Site

Singapore, 258499

Singapore

Novartis Investigative Site

Seoul, 03080

South Korea

Novartis Investigative Site

Seoul, 03722

South Korea

Novartis Investigative Site

Seoul, 05505

South Korea

Novartis Investigative Site

Seoul, 06591

South Korea

Novartis Investigative Site

Basel, 4031

Switzerland

Novartis Investigative Site

Bellinzona, 6500

Switzerland

Novartis Investigative Site

Bern, 3010

Switzerland

Novartis Investigative Site

Taipei, 10002

Taiwan

Novartis Investigative Site

Taipei, 103616

Taiwan

Novartis Investigative Site

Taipei, 11217

Taiwan

Novartis Investigative Site

Taoyuan, 33305

Taiwan