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Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC

NCT06855277 · Novartis
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Official title
A Phase III, Open-label, Multi-center, Randomized Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive Metastatic Castration Resistant Prostate Cancer
About this study
This is a phase III, open label, multicenter randomized study. The study aims at evaluating the superiority of 225Ac-PSMA-617 combined with androgen receptor pathway inhibitor (ARPI) over a change of ARPI or chemotherapy or \[177Lu\]Lu-PSMA-617 (AAA617) in prolonging progression free survival (rPFS). Screening period: At screening, the participants will be assessed for eligibility and will undergo a positron emission tomography (PET)/computed tomography (CT) scan to evaluate PSMA positivity. Only participants with PSMA positive cancer and confirmed eligibility criteria will be randomized. Participants randomized to the investigational arms will receive up to 6 doses of AAA817 10 Mbq +/- 10% given intravenously with or without an ARPI (oral enzalutamide or oral abiraterone) per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Participants randomized to SoC will be treated with an ARPI change (oral enzalutamide or oral abiraterone) or taxane-based chemotherapy (docetaxel or cabazitaxel) or \[177Lu\]Lu-PSMA-617 (AAA617)' per investigator's choice. Treatment with ARPI should continue as per protocol end of treatment criteria. Treatment duration with taxane-based chemotherapy or AAA617will depend on the chosen regimen per the investigator's discretion following local guidelines as per standard of care and product labels and adhere to the protocol end of treatment criteria. Supportive care will be allowed in both arms at the discretion of the investigator and includes available care for the eligible participant according to best institutional practice for mCRPC treatment, including androgen deprivation therapy (ADT). Safety will be assessed routinely during the study. Crossover is not allowed among study arms. The study will be conducted in the USA among other countries globally.
Eligibility criteria
Key Inclusion Criteria: * Signed informed consent must be obtained prior to participation in the study. * Participants must be adults ≥ 18 years of age. * Participants must have an ECOG performance status of 0 to 2. * Participants must have histological, and/or cytological confirmation of adenocarcinoma of the prostate. Participants with mixed histology (neuroendocrine) are not eligible. * Participants who have received taxane-based chemotherapy in mHSPC setting are eligible if they are deemed appropriate for chemotherapy, ARPI change or AAA617 as the next line of therapy in the opinion of the Investigator. Note: Participants who have received taxane-based chemotherapy for mCRPC are excluded. * Participants must not have received taxane-based chemotherapy in mCRPC setting (allowed in mHSPC setting). * Participants must have PSMA-PET positive disease using a PSMA imaging agent that is approved as per protocol. * Participant must have been diagnosed with mCRPC with documented progressive disease while on treatment with ARPI in mHSPC or earlier setting as their last treatment (and did not progress on more than one ARPI). * Participants with deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer, as per local testing, may be enrolled if they had prior exposure to PARPi. Key Exclusion Criteria: * Previous anti-cancer treatment with any approved or investigational radiopharmaceuticals (for example, \[177Lu\]Lu-PSMA, \[177Lu\]-DOTA, or Radium- 223.) * Previous treatment with any external beam radiotherapy including hemi-body radiation within 6 weeks of randomization (within 2 weeks for radiotherapy of localized metastases). * Any prior PARP inhibitor or other systemic anticancer therapy administered for metastatic castration-resistant prostate cancer (mCRPC). Any other approved or investigational systemic therapy (including chemotherapy, immunotherapy, biologics, or monoclonal antibodies) is prohibited within 28 days or 5 half-lives (whichever is shorter) before randomization. Note: Prior ARPI administered in the mHSPC setting or earlier may continue until C1D1. Other protocol-defined inclusion/exclusion criteria may apply.
Study design
Enrollment target: 940 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-07-01
Estimated completion: 2032-11-04
Last updated: 2026-02-24
Interventions
Drug: AAA817Drug: ARPIDrug: Standard of Care
Primary outcomes
  • Radiographic Progression Free Survival (rPFS) (From the date of randomization to the date of the first documented radiographic disease progression using conventional imaging, or death due to any cause, whichever occurs first, assessed up to approximately 40.0 months.)
Sponsor
Novartis Pharmaceuticals · industry
Contacts & investigators
ContactNovartis Pharmaceuticals · contact · novartis.email@novartis.com · 1-888-669-6682
ContactNovartis Pharmaceuticals · contact · +41613241111
InvestigatorNovartis Pharmaceuticals · study_director, Novartis Pharmaceuticals
All locations (55)
Sansum ClinicRecruiting
Santa Barbara, California, United States
Rocky Mountain Cancer CentersRecruiting
Denver, Colorado, United States
Miami Cancer Institute at BaptRecruiting
Miami, Florida, United States
AdventHealthRecruiting
Orlando, Florida, United States
Univ Of Iowa Hospitals And ClinicsRecruiting
Iowa City, Iowa, United States
University of Kansas HospitalRecruiting
Kansas City, Kansas, United States
Wash U School of MedicineRecruiting
St Louis, Missouri, United States
Bassett Medical CenterRecruiting
Cooperstown, New York, United States
Weill Cornell Medicine NY-PresbRecruiting
New York, New York, United States
University of Rochester Medical CtrRecruiting
Rochester, New York, United States
Associated Med Professionals of NYRecruiting
Syracuse, New York, United States
Carolina Urologic Research CenterRecruiting
Myrtle Beach, South Carolina, United States
Urology San AntonioRecruiting
San Antonio, Texas, United States
Swedish Medical CenterRecruiting
Seattle, Washington, United States
Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Novartis Investigative SiteRecruiting
Darlinghurst, New South Wales, Australia
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Adelaide, South Australia, Australia
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São Paulo, São Paulo, Brazil
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São Paulo, São Paulo, Brazil
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Guangzhou, Guangdong, China
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Wuhan, Hubei, China
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Wuhan, Hubei, China
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Nanjing, Jiangsu, China
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Nanjing, Jiangsu, China
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Shenyang, Liaoning, China
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Chengdu, Sichuan, China
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Hangzhou, Zhejiang, China
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Beijing, China
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Beijing, China
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Guangzhou, China
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Shanghai, China
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Shanghai, China
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Shanghai, China
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Hong Kong, Hong Kong
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Hong Kong, Hong Kong
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Gurgaon, Haryana, India
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Mumbai, Maharashtra, India
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Sapporo, Hokkaido, Japan
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Kobe, Hyōgo, Japan
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Yokohama, Kanagawa-ku, Japan
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Chuo Ku, Tokyo, Japan
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Chiba, Japan
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Fukuoka, Japan
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Fukuoka, Japan
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Fukuoka, Japan
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Hiroshima, Japan
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Kyoto, Japan
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Singapore, Singapore
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Singapore, Singapore
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Singapore, Singapore
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Seoul, Korea, South Korea
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Seoul, South Korea
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Kaohsiung City, Taiwan
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Taoyuan District, Taiwan
Novartis Investigative SiteRecruiting
Sutton, Surrey, United Kingdom
Study Comparing AAA817+ARPI Versus Standard of Care in Adult Participants With PSMA-positive mCRPC · TrialPath