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Purpose

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 120 participants will be randomized.

Condition

Eligibility

Eligible Ages
Between 18 Years and 100 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

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 - Castrate level of serum testosterone (< 1.7 nmol/l [50 ng/dl]) on GnRH agonist or antagonist therapy or after bilateral orchiectomy - Participants must have evidence of PSMA-positive disease 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. - PSA Doubling Time (PSADT) of ≤ 10 months - Participants must have adequate organ functions: bone marrow reserve, hepatic & renal

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 soft tissue pelvic disease may be eligible (e.g., participants with enlarged lymph nodes below the aortic bifurcation (N1) are eligible if the short axis of the largest lymph node is <20 mm) - 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); CYP17 inhibitors (e.g., abiraterone acetate, orteronel, galeterone, ketoconazole; radiopharmaceutical agents (e.g., Strontium-89), 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.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
No cross-over allowed
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A 		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
    Administration intravenously once every 6 weeks (1 cycle) for 6 cycles
    Other names:
    • Lutetium [177Lu] vipivotide tetraxetan
    • 177Lu-PSMA-617
  • Drug: AAA517
    Single intravenous dose of approx. 150 Megabecquerel (MBq) prior PSMA-PET scans
    Other names:
    • 68Ga-PSMA-11
  • Drug: Piflufolastat F 18
    Single intravenous dose of approx. 333 Megabecquerel (MBq) prior PSMA-PET scans
  • Drug: ADT
    as prescribed by the local investigator
  • Other: Best supportive care
    as prescribed by the local investigator
Experimental
Arm B 		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
    Administration intravenously once every 6 weeks (1 cycle) for 6 cycles
    Other names:
    • Lutetium [177Lu] vipivotide tetraxetan
    • 177Lu-PSMA-617
  • Drug: AAA517
    Single intravenous dose of approx. 150 Megabecquerel (MBq) prior PSMA-PET scans
    Other names:
    • 68Ga-PSMA-11
  • Drug: Piflufolastat F 18
    Single intravenous dose of approx. 333 Megabecquerel (MBq) prior PSMA-PET scans
  • Drug: ARPI
    Enzalutamide, Darolutamide, Apalutamide as prescribed by the local investigator
  • Drug: ADT
    as prescribed by the local investigator
  • Other: Best supportive care
    as prescribed by the local investigator

Recruiting Locations

UT Health San Antonio Mays Cancer Center
San Antonio, Texas 78229
Contact:
Lorena Fuentes
210-450-1950
fuentesl2@uthscsa.edu

More Details

Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.