Ac225-zadavotide guraxetan (AZD2265) / AstraZeneca - LARVOL DELTA

VECTRA-01: A Phase III study of actinium (225Ac) zadavotide guraxetan (Zada-Gu; AZD2265) versus standard of care (SoC) in pretreated patients (pts) with PSMA-positive (PSMA+) metastatic castration-resistant prostate cancer (mCRPC) (ESMO 2026) - No abstract available

Clinical • Metastases • P3 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01) (clinicaltrials.gov) - P3 | N=670 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Dec 2029 ➔ Jun 2030 | Trial primary completion date: Feb 2029 ➔ Jun 2029

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

PROSPECTOR: Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer (clinicaltrials.gov) - P1/2 | N=152 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01) (clinicaltrials.gov) - P3 | N=670 | Recruiting | Sponsor: AstraZeneca

New P3 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

PROSPECTOR: Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer (clinicaltrials.gov) - P1/2 | N=152 | Not yet recruiting | Sponsor: AstraZeneca

New P1/2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2 | N=85 | Active, not recruiting | Sponsor: Fusion Pharmaceuticals Inc. | Trial completion date: Aug 2030 ➔ May 2027 | Trial primary completion date: Jan 2030 ➔ May 2027

Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • BRCA

AlphaBreak: FPI-2265 (225Ac-PSMA-I&T) for Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2 | N=110 | Active, not recruiting | Sponsor: Fusion Pharmaceuticals Inc. | Trial primary completion date: Jul 2026 ➔ Dec 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • BRCA

Preliminary efficacy and safety results from the (TATCIST) trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&T) for the treatment of metastatic castration-resistant prostate cancer (mCRPC) (AACR 2024) - P2 | "Preliminary efficacy and safety data as of 30Jan24 suggest that FPI-2265 is active in heavily pretreated pts with progressive mCRPC, including pts who received prior Lu therapy. Higher PSMA SUVmean was associated with improved PSA responses, Safety and tolerability were consistent with other published studies of 225Ac-PSMA-RLTs. These initial results support further investigation of FPI-2265 and a new phase 2/3 trial will begin enrolling soon."

Clinical • Metastases • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

AlphaBreak: FPI-2265 (225Ac-PSMA-I&T) for Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: Fusion Pharmaceuticals Inc. | Phase classification: P2/3 ➔ P2

Phase classification • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Targeted Alpha Therapy With 225Actinium-Prostate Specific Membrane Antigen (PSMA)-I&T of Castration-resISTant Prostate Cancer (TATCIST). (clinicaltrials.gov) - P2 | N=115 | Active, not recruiting | Sponsor: Fusion Pharmaceuticals Inc. | Trial completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • BRCA • MSI

FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2 | N=85 | Active, not recruiting | Sponsor: Fusion Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

AlphaBreak: FPI-2265 (225Ac-PSMA-I&T) for Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2/3 | N=100 | Recruiting | Sponsor: Fusion Pharmaceuticals Inc. | N=60 ➔ 100

Enrollment change • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2 | N=85 | Recruiting | Sponsor: Fusion Pharmaceuticals Inc.

New P2 trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Targeted Alpha Therapy with 225Actinium-Prostate Specific Membrane Antigen (PSMA)-I&T of Castration-resISTant Prostate Cancer (TATCIST). (clinicaltrials.gov) - P2 | N=115 | Active, not recruiting | Sponsor: Fusion Pharmaceuticals Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2025 ➔ Jul 2025 | Trial primary completion date: Dec 2024 ➔ Apr 2025

Enrollment closed • Trial completion date • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • BRCA • MSI

FPI-2265: Data from P2/3 AlphaBreak trial (NCT06402331) for mCRPC H2 2025 (AstraZeneca) - Q4 & FY2024 Results

P2/3 data • Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer

FPI-2265: Data from P2/3 AlphaBreak trial (NCT06402331) for mCRPC post 2025 (AstraZeneca) - Q2 2024 Results

P2/3 data • Metastatic Castration-Resistant Prostate Cancer • Oncology

Fusion Pharmaceuticals Announces Clinical Program and Manufacturing Updates (PRNewswire) - "The Company announced today that it has aligned with the FDA on its submitted Phase 2/3 protocol for FPI-2265, a targeted alpha therapy (TAT) targeting prostate specific membrane antigen (PSMA) for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) with progressive disease. The updated development plan includes a Phase 2 dose optimization lead-in, expected to complete enrollment by the end of 2024, and a Phase 3 registrational trial expected to begin in 2025...The Phase 2 portion of the protocol is designed to evaluate the safety and efficacy of FPI-2265 across three dosing regimens in approximately 60 patients with mCRPC...The Phase 2 trial is expected to initiate in the second quarter of 2024 with enrollment completed by year-end. The Company will seek to hold an End of Phase 2 meeting with the FDA to determine the recommended Phase 3 dosing regimen based on analysis of the Phase 2 data..."

Clinical protocol • New P2/3 trial • New trial • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Combinatorial effect of the PSMA targeted alpha therapeutic, [225Ac]-FPI-2265, and olaparib in a pre-clinical prostate cancer tumor model (SNMMI 2024) - "[177Lu]-FPI-2263 exhibited elevated uptake in PSMA-expressing xenografts while demonstrating minimal uptake in PSMA-negative normal tissues. Additionally, [225Ac]-FPI-2265 safely demonstrated therapeutic effectiveness as a monotherapy, with enhanced efficacy observed in combination with olaparib. These results suggest that the combination of [225Ac]-FPI-2265 and olaparib may offer increased therapeutic benefits in patients with prostate cancer and provide support for future clinical investigation."

Preclinical • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Acquisition of Fusion Pharmaceuticals Completed (PRNewswire) - "Fusion Pharmaceuticals...announced the successful completion of the acquisition of all of the issued and outstanding shares of Fusion by a wholly-owned subsidiary of AstraZeneca AB by way of a statutory plan of arrangement under section 192 of the Canada Business Corporations Act, referred to as the Arrangement....The Arrangement complements AstraZeneca's leading oncology portfolio with the addition of the Fusion pipeline of RCs, including their most advanced program, FPI-2265, a potential new treatment for patients with metastatic castration-resistant prostate cancer (mCRPC), and brings new expertise and pioneering R&D, manufacturing and supply chain capabilities in actinium-based RCs to AstraZeneca....As a result of the Arrangement, Fusion has become a wholly owned subsidiary of AstraZeneca, with operations continuing in Canada and the US."

M&A • Metastatic Castration-Resistant Prostate Cancer

Fusion Pharmaceuticals Shareholders Approve Acquisition by AstraZeneca (PRNewswire) - "Fusion Pharmaceuticals...announced that at a special meeting of its shareholders (the 'Shareholders'), held virtually earlier today, the Shareholders voted in favour of the resolution to approve the previously announced plan of arrangement with a wholly-owned subsidiary of AstraZeneca under the Canada Business Corporations Act pursuant to which AstraZeneca will acquire all of the issued and outstanding shares of Fusion (the 'Arrangement')....The arrangement is subject to court approval, as well as other customary closing conditions. Subject to the satisfaction of such conditions, the transaction is expected to be completed in the second quarter of 2024....Fusion's clinical-stage development portfolio includes lead program, FPI-2265, targeting PSMA for mCRPC and novel RCs targeting solid tumors."

M&A • Metastatic Castration-Resistant Prostate Cancer

Fusion Pharmaceuticals Announces First Patient Dosed in the Phase 2 Portion of the AlphaBreak Trial Evaluating FPI-2265 in Metastatic Castration-Resistant Prostate Cancer (PRNewswire) - "Fusion Pharmaceuticals...announced that the first patient has been dosed in the Phase 2 portion of the AlphaBreak trial evaluating FPI-2265 (225Ac-PSMA I&T) in patients with metastatic castration-resistant prostate cancer (mCRPC)....The AlphaBreak trial is a Phase 2/3, randomized, open-label, multicenter study to evaluate the safety and efficacy of FPI-2265 in patients with mCRPC previously treated with 177Lu-PSMA radiotherapy....The Phase 2 portion of the AlphaBreak trial is expected to complete enrollment of approximately 60 patients by the end of 2024....The Phase 3 global registration portion of the AlphaBreak trial will enroll approximately 550 patients and is expected to begin in 2025."

Trial status • Metastatic Castration-Resistant Prostate Cancer

AlphaBreak: FPI-2265 (225Ac-PSMA-I&T) for Patients With PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) (clinicaltrials.gov) - P2/3 | N=60 | Recruiting | Sponsor: Fusion Pharmaceuticals Inc.

Metastases • New P2/3 trial • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Fusion Pharmaceuticals Reports First Quarter 2024 Financial Results and Announces Clinical Program Updates (Canada Newswire) - "Patient enrollment and dosing is ongoing in the Phase 1, multi-center, open-label clinical trial designed to investigate the safety, tolerability, dosimetry, biodistribution, and pharmacokinetics of FPI-2059 as well as preliminary anti-tumor activity in participants with NTSR1 expressing advanced metastatic solid tumors....R&D Expenses: Research and development expenses for the first quarter of 2024 were $21.3 million, compared to $15.9 million for the same period in 2023. The increase was primarily due to an increase in FPI-2265 program-related costs for our Phase 2 clinical trial of FPI-2265 in patients with mCRPC, and an increase in manufacturing-related costs."

Commercial • Trial status • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Metastatic Castration-Resistant Prostate Cancer • Oncology • Prostate Cancer • Solid Tumor

Fusion Pharmaceuticals Announces Presentation of Interim Data from the Phase 2 TATCIST Clinical Trial Evaluating FPI-2265 at the AACR Annual Meeting 2024 (PRNewswire) - P2 | N=115 | TATCIST (NCT05219500) | Sponsor: Fusion Pharmaceuticals Inc. | "The results are being presented at the AACR 2024 Annual Meeting....As of the March 1, 2024 data cutoff, 35 patients received at least one dose of FPI-2265, with 25 patients having at least 12 weeks of follow-up....From the efficacy-evaluable patient population, PSA50 (≥50% decline in prostate-specific antigen by 12 weeks after first treatment) response was achieved in 10 out of 20 patients (50%) regardless of prior lutetium treatment. PSA50 was achieved in 61% of lutetium-naïve participants and 42% of lutetium-treated participants....FPI-2265 demonstrated meaningful improvement in secondary endpoints which include maximum % PSA decline, and independent reviewer-assessed response rates....Fusion is advancing a Phase 2/3 trial for FPI-2265 in patients with mCRPC....The Phase 2 portion is expected to be initiated in the second quarter of 2024. A Phase 3 global registrational trial is expected..."

New P2/3 trial • New P3 trial • P2 data • Metastatic Castration-Resistant Prostate Cancer

Fusion Pharmaceuticals Reports Fourth Quarter and Full Year 2023 Financial Results and Announces Clinical Program Updates (PRNewswire) - "FPI-2265:...Following analysis of the Phase 2 data and an end of Phase 2 meeting to determine the recommended Phase 3 dosing regimen with the FDA, a Phase 3 global registrational trial in approximately 550 patients is expected to begin in 2025.....The Company is also pursuing the opportunity to potentially move this therapeutic candidate into earlier lines of treatment with combinations of FPI-2265 and olaparib. Fusion expects to initiate a combination trial in the first half of this year."

New P3 trial • New trial • Metastatic Castration-Resistant Prostate Cancer