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EP-4739356-A1 - IMAGING METHODS AND AGENTS FOR GRADING AND STAGING AND SUBSEQUENT TREATMENT OF PROSTATE CANCER IN A PATIENT

EP4739356A1EP 4739356 A1EP4739356 A1EP 4739356A1EP-4739356-A1

Abstract

The invention provides methods of using piflufolastat Fl 8 as an imaging agent for use in combination with PET/CT or PET/MRI for the early detection of regional LNI and distant metastases in patients who have been graded as having favorable intermediate risk (FIR) prostate cancer (PCa). In accordance with the methods of the invention, piflufolastat Fl 8 PET/CT or PET MRI will detect EPI, SVI, regional LNI or distant metastases or upgrade patients to ISUP grade >3 PCa invention in at least 5% of FIR patients previously assessed and staged by standard of care (SOC) methods including CT or MRI. Early detection of more advanced disease may prompt more aggressive treatment to manage prostate cancer at an earlier stage and may thereby improve patient outcomes such as progression free survival (PFS) and overall survival (OS) of the patient.

Inventors

  • TESLENKO, Iryna
  • PROVOST, JEAN-CLAUDE

Assignees

  • Progenics Pharmaceuticals, Inc.
  • Teslenko, Iryna
  • Provost Jean-Claude

Dates

Publication Date
20260513
Application Date
20240626

Claims (7)

  1. 1. A method of using piflufolastat Fl 8 as a radioligand imaging agent to grade or stage a prostate cancer patient who has been previously graded as having favorable intermediate risk (FIR) prostate cancer or has been previously assigned less than a grade 3 PCa on the International Society of Urological Pathology (ISUP) grading system, comprising the steps of: (i) administering piflufolastat Fl 8 to a prostate cancer patient who has been assigned FIR status or has been assigned less than a grade 3 PCa on the ISUP grading system; (ii) imaging the patient, optionally within 1-4 hours, after injection of piflufolastat Fl 8 by PET/CT or PET/MRI; (iii) obtaining the PET/CT or PET/MRI image of the patient; (iv) upstaging or upgrading the patient’s prostate cancer if the image identifies an extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node involvement (LNI), or ISUP grade >3 PCa; and (v) optionally changing the prostate cancer treatment strategy of the patient from active surveillance therapy to active therapy if the patient’s prostate cancer is upgraded or upstaged.
  2. 2. The method of claim 1 wherein the prostate cancer patient is being treated with active surveillance therapy.
  3. 3. The method of claim 2 wherein a patient’s prostate cancer is upgraded or upstaged, and the medical management of the patient’s disease is changed from active surveillance to active therapy.
  4. 4. The method of claim 1 wherein the administering step comprises administration by injection or infusion into the patient.
  5. 5. A method of treating prostate cancer in a patient population of prostate cancer patients who have been previously graded as having favorable intermediate risk (FIR) prostate cancer or who have been previously assigned less than a grade 3 PCa on the International Society of Urological Pathology (ISUP) grading system and who are currently being treated with active surveillance therapy, comprising the steps of: (i) administering piflufolastat Fl 8 to an FIR prostate cancer patient population of at least 2 patients graded as having FIR prostate cancer; (ii) imaging the patients in the patient population, optionally within 1-4 hours, after injection of piflufolastat Fl 8 by PET/CT or PET/MRI; (iii) obtaining the PET/CT or PET/MRI image from each of the patients in the patient population wherein at least 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75% or more of the patients in the patient population have images that identify an extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node involvement (LNI), or ISUP grade >3 PCa, and (iv) changing the treatment of one or more patients in the patient population from active surveillance therapy to active therapy if the patient’s image identifies an extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node involvement (LNI), or ISUP grade >3 PCa.
  6. 6. The method of claim 5 wherein the administering step comprises administration by injection or infusion into the patient.
  7. 7. The method of claim 5 wherein the FIR PCa patient population comprises at least 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more FIR PCa prostate cancer patients.

Description

IMAGING METHODS AND AGENTS FOR GRADING AND STAGING AND SUBSEQUENT TREATMENT OF PROSTATE CANCER IN A PATIENT RELATED APPLICATIONS This application claims the benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional Application No. 63/512027, filed July 5, 2023, the entire contents of which are incorporated herein by reference. BACKGROUND Prostate cancer (PCa) is one of the most common cancers among men in the United States (U.S.), and the incidence rate continues to rise. The occurrence of new PCa cases is estimated to reach 288,300 in 2023, and 299,010 in 2024. Second only to lung cancer, PCa is a common cause of cancer-related death in men, with 34,700 deaths projected in the U.S. during 2023, and 35,250 in 2024. Initial risk stratification and staging is a critical step in defining PCa prognosis and providing treatment recommendations. The accurate detection of clinically significant cancer including disease extension through the prostatic capsule, either confined to the prostate gland or with extraprostatic growth to the adjacent structures, lymph node (LN) or distant sites, is essential in determining a patient’s risk group and guiding the most appropriate patient-specific therapeutic strategy. The extraprostatic extension (EPE) is a strong adverse prognostic factor associated with higher recurrence rates and with decreased long-term survival. Extraprostatic extension and lymph node involvement (LNI) upstages a patient to a “very high-risk” group, which requires more aggressive local treatment and androgen deprivation therapy (ADT). In contrast, localized favorable risk prostate cancer that has not spread outside the prostate may be suitable for active surveillance. Imaging modalities such as conventional radiography, ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy, single-photon emission computed tomography (SPECT), and/or PET are used in the staging and characterization of PCa in addition to digital rectal examination (DRE). Multiparametric (mp) MRI is a preferred method for abdominal/pelvic staging over CT and demonstrates equivalence to CT efficacy in pelvic LN evaluation. It has been shown, however, that routine staging using CT or MRI lacks sufficient sensitivity and accuracy, especially for detection of sub-centimeter LN metastasis. Early detection of clinically significant disease, extraprostatic extension (EPE), and seminal vesical invasion (SVI) may change medical management, particularly in FIR patients, and improve treatment outcomes; however, the use of imaging agents in prostate-specific membrane antigen (PSMA) PET/CT or PET/MRI and their impact on patient management and staging in the FIR in this group has not been explored. SUMMARY The probability of nodal and distant metastasis in patients with very-low, low, and favorable intermediate risk (FIR) PCa is considered minimal. However, it has been reported that patients assigned to the FIR category are more likely than low-risk patients to have adverse pathological findings (upstaging and upgrading) at radical prostatectomy (RP) with a trend toward shorter recurrence-free survival. Seminal vesicle invasion (SVI) is a poor prognostic factor for prostate cancer and is associated with local relapse, distant metastasis, and early biochemical recurrence. Routine staging using CT or MRI lacks sufficient sensitivity and accuracy especially for detection of sub-centimeter LN metastasis. Early detection of clinically significant disease, extraprostatic extension (EPE), and SVI may change medical management in FIR patients and improve treatment outcomes for patients initially staged as FIR. For example, many FIR prostate patients are often managed by active surveillance protocols which include prostate-specific antigen testing every 3-6 months, digital rectal examination at least once a year, and serial prostate biopsies every 6 to 12 months or at longer intervals. Patients who are reclassified into a higher risk category may be offered more aggressive active therapy such as radiation therapy, local treatments such as surgery (e.g., prostatectomy), focal therapies (e.g., high- intensity focused ultrasound), systemic treatments such as androgen deprivation hormonal therapy (ADT) chemotherapy, immunotherapy, radioligand therapy (RLT) by infusion at an earlier stage in the disease which may improve patient outcomes. Preferably, the invention provides a method of using piflufolastat Fl 8 as a radioligand imaging agent to upgrade and/or upstage a prostate cancer patient who has been previously graded as having favorable intermediate risk (FIR) prostate cancer or has been assigned less than a grade 3 PCa on the International Society of Urological Pathology (ISUP) grading system, comprising the steps of: (i) administering, preferably by injection or infusion, piflufolastat Fl 8 to a prostate cancer patient who has been assigned FIR status or has been assigned less than a grade 3 PCa on the Internat