FPI-2265 Dosing Commences in Phase 2 AlphaBreak Trial for mCRPC


The first patient has been dosed in the phase 2 AlphaBreak trial with FPI-2265 for the treatment of metastatic castration-resistant prostate cancer, marking a significant milestone in advanced cancer treatment.

Conceptual image for viral ethiology of prostate cancer. 3D illustration showing viruses infecting prostate gland which develops cancerous tumor: © Dr_Microbe - stock.adobe.com

Conceptual image for viral ethiology of prostate cancer. 3D illustration showing viruses infecting prostate gland which develops cancerous tumor: © Dr_Microbe - stock.adobe.com

About the AlphaBreak Trial of FPI-2265 in mCRPC

Trial Name: 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)

ClinicalTrials.gov Identifier: NCT06402331

Sponsor: Fusion Pharmaceuticals Inc.

Recruitment Contact: Clinical Trials Fusion Pharmaceuticals Inc, (888) 506-4215, clinicaltrials@fusionpharma.com

Completion Date: January 23, 2031

The phase 2 portion of the AlphaBreak trial (NCT06402331) evaluating FPI-2265 (225Ac-PSMA I&T) has dosed its first patient with metastatic castration-resistant prostate cancer (mCRPC).1

"Actinium-based [prostate specific membrane antigen (PSMA)]-targeting [radioconjugates (RCs)] have demonstrated compelling safety and clinical activity, which is supported by Fusion's encouraging data from the phase 2 TATCIST trial [NCT05219500] reported recently at the [American Association for Cancer Research] Annual Meeting. We believe FPI-2265 represents an important potential new treatment option for patients with mCRPC, and with the initiation of the AlphaBreak trial we are pleased to move forward," said Dmitri Bobilev, MD, chief medical officer of Fusion Pharmaceuticals Inc, in a press release.

FPI-2265, an actinium-225-based PSMA which targets RC, is being explored in a phase 2 trial for the treatment of patients with mCRPC.

Actinium-225, with its emission of alpha particles, represents a significant potential advancement in cancer therapy. These alpha particles show potential for more potent cancer killing by delivering a high dose of radiation over a limited range. Additionally, actinium-225 has targeted delivery which can minimize damage to surrounding healthy tissue.

AlphaBreak is a randomized, open-label, multicenter, phase 2/3 trial assessing the safety and efficacy of FPI-2265 in patients with mCRPC. All those enrolled in the trial must have been previously treated with 177Lu-PSMA (Pluvicto) radiotherapy.2

For phase 2 of the trial, male patients aged 18 years and older with an ECOG performance status 0 or 1, a diagnosis of adenocarcinoma of prostate proven by histopathology, progressive mCRPC, and a positive PSMA PET/CT scan were eligible for enrollment. Patients were required to have had prior orchiectomy and/or ongoing androgen deprivation therapy, a castrate level of serum/plasma testosterone, and adequate organ function. Additionally, patients with known BRCA mutations should have received FDA-approved therapies, like a PARP inhibitor, per investigator discretion.

Primary end points of the study include frequency, duration, and severity of treatment-emergent adverse events, and frequency and proportion of participants with prostate specific antigen response.

In the phase 2 dose-optimization portion of the study, experts are evaluating safety and/or benefits of 2 alternative dosing regimens to see if there are added benefits compared with the agent given at a dose of 100 kBq/kg every 8 weeks, a regimen which was previously studied. AlphaBreak’s phase 2 portion is anticipated to finalize enrollment of about 60 patients by the end of 2024.1

Once the data from the phase 2 study are analyzed and a phase 2 meeting with the FDA to determine the recommended phase 3 dosing regimen is completed, the phase 3 global registration portion of the AlphaBreak trial will begin. This portion of the study plans to enroll approximately 550 patients. Investigators expect phase 3 to begin in 2025.

"Despite recent advances in the field, we see many patients with mCRPC still in need of additional treatment options, especially after progressing on lutetium-based radiotherapy. It is encouraging to see the promising clinical activity and good safety profile demonstrated by FPI-2265. The initiation of the AlphaBreak trial brings us a step closer to addressing the gap for patients and providing this needed treatment option," said investigator Luke Nordquist, MD, FACP, XCancer chief executive officer, in a press release.

  1. Fusion Pharmaceuticals announces first patient dosed in the phase 2 portion of the AlphaBreak trial evaluating FPI-2265 in metastatic castration-resistant prostate cancer. News release. Fusion Pharmaceuticals Inc. May 9, 2024. Accessed May 10, 2024. https://tinyurl.com/2su9xc2z
  2. FPI-2265 (225Ac-PSMA-I&T) for patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) (AlphaBreak). ClinicalTrials.gov. Updated May 8, 2024. Accessed May 10, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06402331
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