Clinical trial NCT06402331: FPI-2265 (225Ac-PSMA-I&T) for Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Official title: A Phase 2/3, Randomized, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of FPI-2265 (225Ac-PSMA-I&T) in Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC), Previously Treated With 177Lu-PSMA Radioligand Therapy (RLT)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Metastatic Castration-resistant Prostate Cancer
Keywords: mCRPC
225Ac-PSMA-I&T
Radioligand therapy
Lead sponsor: Fusion Pharmaceuticals Inc.
Sponsor class: INDUSTRY
First posted: 2024-05-07
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I\&T). Patient population is adult participants with PSMA positive mCRPC who have had previous treatment with with 177Lu-PSMA-617 or another 177Lu-PSMA radioconjugate (RC). The purpose of the study is to determine the safety and tolerability, and recommended dose and regiment of FPI-2265.

Detailed description: This is an open-label, randomized, multicenter study of FPI-2265 (225Ac-PSMA-I\&T). The purpose of the dose optimization segment (Phase 2) is to determine the recommended FPI-2265 dose and regimen. Conclusions from Phase 2 will be based on safety, tolerability, and anti-tumor activity.

Screening Period: At screening, participants will be assessed for eligibility and 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 will enter the treatment period and receive investigational doses of FPI2265 according to the dose level and schedule as specified per proposed dose arm.

Part A participants will enroll 1:1:1 at three dose level/schedules, to arms 1, 2 or 3

Part B participants will enroll after completion of part A, in a 1:1 randomization scheme to arms 6 or 7.

Once Part A is fully enrolled and participants have been followed for at least 12 weeks, data from Arm 1 and 2 will be analyzed to assess the the feasibility of enrolling participants to arms 4 and 5.

All participants will be monitored and assessed for efficacy response, disease progression and adverse events.

Supportive care will be allowed in all 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).

Follow-up after end of treatment visit will proceed for 5 years.

5 participants will be enrolled into a dosimetry substudy (open at select sites only). Dosimetry substudy participants will be administered one dose at of FPI2265 and proceed with dosimetric assessments will be taken at a number of timepoints after dose administration.

Eligibility criteria: Key Inclusion Criteria:

* Phase 2: Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Diagnosis of adenocarcinoma of prostate proven by histopathology.
* Must have had prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum/plasma testosterone
* Progressive mCRPC at time of study entry.
* Must have been previously treated with lutetium-PSMA therapy (lutetium-177 vipivotide tetraxetan or other lutetium-177-PSMA RLT). Treatment must have been completed \>6 weeks prior to the first dose of study drug.
* Participants with known BRCA mutations should have received FDA-approved therapies such as PARP inhibitors, per Investigator discretion.
* Positive PSMA PET/CT scan
* Adequate organ function
* For participants who have partners of childbearing potential: Partner and/or participant must not be planning to conceive and must use a method of birth control with adequate barrier protection deemed acceptable by the Principal Investigator during the study treatment and for six months after last study drug administration.

Key Exclusion Criteria:

* Participants who received more than two prior lines of cytotoxic chemotherapy for CRPC.
* Phase 2: participants who progress prior to administration of the 3rd cycle of prior treatment with 177Lu-PSMA therapy
* All prior treatment-related adverse events must have resolved to Grade ≤1 (CTCAE v5.0). Alopecia and stable persistent Grade 2 peripheral neuropathy may be allowed at the discretion of the Investigator.
* Participants with known, unresolved, urinary tract obstruction are excluded.
* Administration of any systemic cytotoxic or investigational therapy ≤30 days of the first dose of study treatment or five half-lives, whichever is shorter. Completion of large-field external beam radiotherapy ≤four weeks of the first dose of study treatment.
* Participants with a history of central nervous system (CNS) metastases are excluded except those who have received therapy
* Participants with any liver metastases will be excluded from the Phase 2 segment of the study.
* Participants with skeletal metastases presented as a superscan on a ⁹⁹ᵐTc bone scan.
* Previous or concurrent cancer that is distinct from the cancer under investigation in primary site or histology, except treated cutaneous basal cell carcinoma or squamous cell carcinoma and superficial bladder tumors. Any cancer curatively treated \>two years prior to the first dose of treatment is permitted.
* Concurrent serious (as determined by the investigator) medical conditions
* Major surgery ≤30 days prior to the first dose of study treatment.

Primary outcomes:
measure: Frequency, duration, and severity of treatment-emergent adverse events (TEAEs)
timeFrame: From first dose until end of long-term follow-up, 5 years from end of treatment visit.
measure: Frequency and proportion of participants with PSA50 response
timeFrame: From first dose until 12 weeks after the first administered dose of FPI-2265.
Secondary outcomes:
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Irvine
country: United States
facility: Hoag Health Center Irvine
state: California
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: UCSF School of Medicine
state: California
city: Miami
country: United States
facility: Biogenix Molecular, LLC
state: Florida
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Glen Burnie
country: United States
facility: United Theranostics
state: Maryland
city: Grand Rapids
country: United States
facility: BAMF Health
state: Michigan
city: Saint Louis
country: United States
facility: SSM Health Saint Louis University Hospital
state: Missouri
city: Omaha
country: United States
facility: XCancer
state: Nebraska
city: Albuquerque
country: United States
facility: New Mexico Oncology Hematology Consultants Ltd.
state: New Mexico
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at NYU Langone
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center - NYC
state: New York
city: Portland
country: United States
facility: Oregon Health and Science University (OHSU, Knight Cancer Center)
state: Oregon
city: Dallas
country: United States
facility: VA North Texas Health Care System, Nuclear Medicine Service
state: Texas
city: Dallas
country: United States
facility: The University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: U.T. MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Fusion Pharmaceuticals Inc.
name: Keith Barnett
role: STUDY_DIRECTOR
References: