A Phase II Study of AAA617 Alone and AAA617 in Combination With ARPI in Patients With PSMA PET Scan Positive CRPC

NCT05849298 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: CAAA617B122032022-503040-41-00
• Study Type: interventional
• Target: 49
• Locations: 11 countries
• Sites: 41

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of AAA617 alone (Lutetium \[177Lu\] vipivotide tetraxetan) and in combination with an Androgen Receptor Pathway Inhibitors (ARPI) in participants with PSMA-positive, castration-resistant prostate cancer and no evidence of metastasis in conventional imaging (CI) (i.e., CT/MRI and bone scans).

Conditions

Prostatic Neoplasm

Keywords

Prostate-specific membrane antigen (PSMA); Lutetium [177Lu] vipivotide tetraxetan (AAA617); Androgen Receptor Pathway Inhibitors (ARPI); Enzalutamide; Darolutamide; Apalutamide; Castration Resistant Prostate Cancer; Androgen Deprivation Therapy; gallium [68Ga] gozetotide (AAA517); piflufolastat F 18

Outcome Measures

Primary Outcomes (1)

• PSA response

  PSA response is defined as the time of PSA nadir value of =\< 0.2 ng/mL is confirmed by a second (the next) PSA measurement at least 4 weeks later

  From randomization until PSA nadir value of =< 0.2 ng/mL that is confirmed by a second (the next) PSA measurement >= 4 weeks later, up to 5 years

Secondary Outcomes (16)

• Metastatic Free Survival (MFS)

  From date of randomization until date of progression or date of death whichever occurs first, up to 5 years

• Radiographic Progression Free Survival (rPFS)

  From date of randomization until date of radiographic progression or date of death from any cause, whichever comes first, up to 5 years

• Overall Survival (OS)

  From date of randomization until date of death from any cause, up to 5 years

• second Progression Free Survival (PFS2)

  From date of randomization until date of second progression or date of death from any cause, whichever comes first, assessed up to 5 years

• Time to symptomatic progression

  From date of randomization until development of a symptomatic skeletal event, new systemic anti-cancer therapy, surgical intervention or radiation therapy, whichever occurs first, up to 5 years

Study Arms (2)

Arm A

EXPERIMENTAL

Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. ADT must be ongoing; Best supportive care is allowed.

Drug: AAA617; Drug: AAA517; Drug: Piflufolastat F 18; Drug: ADT; Other: Best supportive care

Arm B

EXPERIMENTAL

Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. In addition of SOC (ADT plus choice of ARPI as per physician's decision), Best supportive care is allowed.

Drug: AAA617; Drug: AAA517; Drug: Piflufolastat F 18; Drug: ARPI; Drug: ADT; Other: Best supportive care

Interventions

AAA617 DRUG

Administration intravenously once every 6 weeks (1 cycle) for 6 cycles

Also known as: Lutetium [177Lu] vipivotide tetraxetan, 177Lu-PSMA-617

Arm A; Arm B

AAA517 DRUG

Single intravenous dose of approx. 150 Megabecquerel (MBq) prior PSMA-PET scans

Also known as: 68Ga-PSMA-11

Arm A; Arm B

Piflufolastat F 18 DRUG

Single intravenous dose of approx. 333 Megabecquerel (MBq) prior PSMA-PET scans

Arm A; Arm B

ADT DRUG

as prescribed by the local investigator

Arm A; Arm B

Best supportive care OTHER

as prescribed by the local investigator

Arm A; Arm B

ARPI DRUG

Enzalutamide, Darolutamide, Apalutamide as prescribed by the local investigator

Arm B

Eligibility Criteria

• Age: 18 Years - 100 Years
• Gender Eligibility Details: Prostate cancer study
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be adults ≥ 18 years of age with signed informed consent prior to participation to study
• Histologically or cytologically confirmed prostate cancer
• Participants must have ongoing androgen deprivation therapy with a GnRH agonist/antagonist or prior bilateral orchiectomy at the time of randomization. Intermittent administration of ADT is accepted before randomization if criterion for serum testosterone is met
• Castrate level of serum testosterone (\< 1.7 nmol/l \[50 ng/dl\]) on GnRH agonist or antagonist therapy (continuous/intermittent) or after bilateral orchiectomy prior to randomization
• Participants must have evidence of PSMA-positive disease (N1 or M1) as seen on a AAA517 or piflufolastat F 18 PET/CT scan at baseline as determined by Blinded Independent Central Review (BICR) based on the methodology proposed in the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) (Eiber et al 2018). Participants with M1 disease only on PSMA PET scan are allowed to participate
• Participants must have a negative conventional imaging for M1 disease.
• Participants must have adequate organ functions: bone marrow reserve, hepatic \& renal

You may not qualify if:

• Prior or present evidence of metastatic disease as assessed by CT/MRI locally for soft tissue disease and whole-body radionuclide bone scan for bone disease. Exception: Participants with pelvic disease may be eligible (e.g., participants with enlarged lymph nodes below the bifurcation of common iliac arteries (N1))
• Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which is manageable with best available standard of care (incl. pads, drainage) are allowed
• Active clinically significant cardiac disease; history of seizure or condition that may pre-dispose to seizure which may require treatment with surgery or radiation therapy
• Prior therapy with: second generation anti-androgens (e.g., enzalutamide, apalutamide and darolutamide) \< 3 months before randomization; CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galeterone) \< 3 months before randomization; ketoconazole (short duration ketoconazole treatment (\<28 days) is permitted); radiopharmaceutical agents (e.g., Strontium-89) if wash-out period of at least 3 months is not completed, PSMA-targeted radioligand therapy; immunotherapy (e.g., sipuleucel-T); chemotherapy, except if administered in the adjuvant/neoadjuvant setting, completed \> 2 years before randomization; any other investigational agents for CRPC; use of estrogens, 5-α reductase inhibitors (finasteride, dutasteride), other steroidogenesis inhibitors (aminoglutethimide) or first-generation anti-androgens (bicalutamide, flutamide, nilutamide, cyproterone) within 28 days before randomization; radiation therapy (external beam radiation therapy \[EBRT\] and brachytherapy within 28 days before randomization
• Other concurrent cytotoxicity chemotherapy, immunotherapy, radioligand therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor, biological therapy or investigational therapy

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (41)

Urology Associates of Mobile

Mobile, Alabama, 36608, United States

Location

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

Location

University Of Florida

Jacksonville, Florida, 32218, United States

Location

University Cancer and Blood Center LLC

Athens, Georgia, 30607, United States

Location

Urology Of Indiana

Indianapolis, Indiana, 46254, United States

Location

Unity Point Clinic

Des Moines, Iowa, 50323, United States

Location

Urology Cancer Center PC

Omaha, Nebraska, 68130, United States

Location

Associated Med Professionals of NY

Syracuse, New York, 13210, United States

Location

Oregon Urology Institute

Springfield, Oregon, 97477, United States

Location

Wellspan York Hospital

York, Pennsylvania, 17403, United States

Location

Coastal Cancer Center

Conway, South Carolina, 29526, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Carolina Regional Cancer Center

Myrtle Beach, South Carolina, 29577, United States

Location

Urology Clinic of North Texas

Dallas, Texas, 75231, United States

Location

Univ of Texas Southwest Med Center

Dallas, Texas, 75390-9034, United States

Location

Rio Grande Urology

El Paso, Texas, 79912, United States

Location

Houston Methodist Hospital

Houston, Texas, 77030, United States

Location

UT Health San Antonio Mays Cancer Center

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

São Paulo, São Paulo, 01308-050, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05652-000, Brazil

Location

Novartis Investigative Site

Halifax, Nova Scotia, B3H 2Y9, Canada

Location

Novartis Investigative Site

Toronto, Ontario, M5G 2M9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2X 1R9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H3T 1E2, Canada

Location

Novartis Investigative Site

Olomouc, 779 00, Czechia

Location

Novartis Investigative Site

Angers, 49055, France

Location

Novartis Investigative Site

Brest, 29609, France

Location

Novartis Investigative Site

Strasbourg, 67000, France

Location

Novartis Investigative Site

Strasbourg, F 67085, France

Location

Novartis Investigative Site

Berlin, 10249, Germany

Location

Novartis Investigative Site

Genova, GE, 16132, Italy

Location

Novartis Investigative Site

Roma, RM, 00128, Italy

Location

Novartis Investigative Site

Milan, 20141, Italy

Location

Novartis Investigative Site

Naples, 80131, Italy

Location

Novartis Investigative Site

Kielce, 25-640, Poland

Location

Novartis Investigative Site

Singapore, 169608, Singapore

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 05505, South Korea

Location

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Novartis Investigative Site

Barcelona, 08036, Spain

Location

Novartis Investigative Site

Madrid, 28040, Spain

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Lutetium; Lutetium-177; Pluvicto; gallium 68 PSMA-11; 2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Lanthanoid Series Elements; Metals, Rare Earth; Elements; Inorganic Chemicals; Transition Elements; Metals

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

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

Model Details: No cross-over allowed

Study Record Dates

• First Submitted: April 27, 2023
• First Posted: May 8, 2023
• Study Start: January 3, 2024
• Primary Completion (Estimated): December 23, 2026
• Study Completion (Estimated): December 23, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (4); SG (1); DE (1); IT (4); CZ (1); PL (1); CA (4); US (18); ES (3); BR (2); KR (2)