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

Phase 2Active Not RecruitingNCT05849298

Novartis Pharmaceuticals49 enrolled

Overview

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). Approximately 80 participants will be randomized.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Prostatic Neoplasm

Interventions

AAA617DRUG

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

AAA517DRUG

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

Piflufolastat F 18DRUG

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

Eligibility

Sex: MALEMin age: 18 YearsMax age: 100 Years

Medical Language ↔ Plain English

Key Inclusion criteria * 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 Key Exclusion criteria * 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 Other protocol-defined inclusion/exclusion criteria may apply.

Locations (50)

Outcomes

Primary Outcomes

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

Time frame: 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

Metastatic Free Survival (MFS)

MFS is defined as the time from date of randomization to the first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging using RECIST 1.1 or death.

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

Radiographic Progression Free Survival (rPFS)

rPFS is defined as the time from the date of randomization to the date of first documented radiographic disease progression by conventional imaging assessed using RECIST 1.1 or death.

Time frame: 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)

OS defined as date of death due to any cause

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

second Progression Free Survival (PFS2)

PFS2 defined as time from the date of randomization to the date of first documented disease progression by investigator's assessment (PSA, radiographic, symptomatic, or any combination) on next line of therapy subsequent to MFS event or death due to any cause, whichever occurs first

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

Data from ClinicalTrials.gov

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Enzalutamide, Darolutamide, Apalutamide as prescribed by the local investigator

ADTDRUG

as prescribed by the local investigator

Best supportive careOTHER

as prescribed by the local investigator

Urology Associates of Mobile

Mobile, Alabama, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

University Of Florida

Jacksonville, Florida, United States

University Cancer and Blood Center LLC

Athens, Georgia, United States

Urology Of Indiana

Indianapolis, Indiana, United States

Unity Point Clinic

Des Moines, Iowa, United States

Urology Cancer Center PC

Omaha, Nebraska, United States

Associated Med Professionals of NY

Syracuse, New York, United States

Oregon Urology Institute

Springfield, Oregon, United States

Wellspan York Hospital

York, Pennsylvania, United States

...and 40 more locations

Time to symptomatic progression

Time to symptomatic progression will be defined as the time from the date of randomization to the date of first documented event for any of the following: * Development of a symptomatic skeletal event (SSE) * Pain progression or worsening of disease-related symptoms requiring initiation of a new systemic anti-cancer therapy * Development of clinically significant symptoms due to loco-regional tumor progression requiring surgical intervention or radiation therapy

Time frame: 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

Time to initiation of cytotoxic chemotherapy

Time to initiation of cytotoxic chemotherapy will be defined as the time from the date of randomization to the date of first documented dose of new cytotoxic chemotherapy being administered to the participant

Time frame: From the date of randomization to the date of first documented dose of new cytotoxic chemotherapy administered to the participant, up to 5 years

Time to first symptomatic skeletal event (TTSSE)

TTSSE is defined as the time from the date of randomization to the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death due to any cause, whichever occurs first

Time frame: From the date of randomization to the date of the first new symptomatic pathological bone fracture, spinal cord compression, orthopedic surgical intervention, radiation therapy or death due to any cause, whichever occurs first, up to 5 years

Time to distant metastasis development

Time to distant metastasis development is defined as the time from the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging using RECIST 1.1

Time frame: From the date of randomization to the date of first evidence of radiographically detectable bone or soft tissue distant metastasis, up to 5 years

Time to local radiological progression

Time to local radiological progression is defined as the time from the date of randomization to the date of first documented local radiographic disease progression by conventional imaging using RECIST 1.1

Time frame: From the date of randomization to the date of first documented local radiographic disease progression, up to 5 years

Time to initiation or change in therapy

Time to initiation or change in therapy is defined as the time from the date of randomization to the date of first documented dose of a new / change in therapy being administered to the participant

Time frame: From the date of randomization to the date of first dose of a new / change in therapy, up to 5 years

Time to PSA response

Time to PSA response is calculated as the time from randomization to PSA response with a PSA nadir value of =\< 0.2ng/mL.

Time frame: From randomization to PSA response, up to 5 years

PSA50 response

PSA50 response is defined as the proportion of participants who have a \>= 50% decrease in PSA from baseline that is confirmed by a second (the next) PSA measurement \>= 4 weeks later