Prostate and Rare Cancer Agents Nab FDA Fast Track Status

The FDA has granted fast track designation to 2 investigational agents: VIR-5500, a PSMA-targeted, dual-masked T-cell engager (TCE) for metastatic castration-resistant prostate cancer (mCRPC), and [²¹²Pb]PSV359, a fibroblast activation protein (FAP)-directed alpha-particle therapy for adults with locally advanced unresectable and/or metastatic FAP-positive solitary fibrous tumors (SFTs).¹^,²

Fast track status aims to speed development and review of therapies for serious conditions with unmet need, bringing more frequent FDA interactions and possible eligibility for rolling, accelerated, or priority review.¹^,²

VIR-5500 Heads Toward Phase 3 in Late-Line mCRPC

Updated dose-escalation findings from the open-label, nonrandomized phase 1 trial (NCT05997615), presented at the 2026 ASCO Genitourinary Cancers Symposium, showed dose-dependent activity with VIR-5500 monotherapy in heavily pretreated mCRPC.³ In cohorts receiving at least 3000 µg/kg every 3 weeks (n = 22), 82% (14/17) of patients evaluable for prostate-specific antigen (PSA) had a PSA decline of 50% or more, and 53% (9/17) had a decline of 90% or more. The objective response rate was 45% (5/11) in patients with measurable disease; 4 responses were confirmed and 1 was pending. PSMA positron emission tomography (PET) showed shrinkage across multiple lesions, including visceral metastases.³

“Receiving fast track designation reflects the potential of VIR-5500 to address an area of serious unmet need in late-line mCRPC and the strong momentum we have achieved with Astellas as we prepare to enter pivotal phase 3 development in 2027. We look forward to working with the FDA to rapidly advance the development of VIR-5500 for people living with mCRPC,” Marianne De Backer, president and chief executive officer of Vir Biotechnology, stated in a press release. Vir is codeveloping the agent with Astellas Pharma.¹

Among all 58 patients given monotherapy, no dose-limiting toxicities (DLTs) occurred. Grade 3 or higher treatment-related adverse events affected 12% (7/58), and cytokine release syndrome occurred in 50% (29/58), mostly grade 1 fever, without prophylactic steroids. Patients had a median of 4 prior lines of therapy, and nearly half had visceral disease.³

VIR-5500 pairs a bispecific PSMA- and CD3-binding TCE with PRO-XTEN masking, which stays inactive until tumor-specific proteases cleave the mask in the tumor microenvironment. This aims to sidestep the toxicity that has limited TCEs in solid tumors and extends half-life, potentially allowing less frequent dosing.¹

The phase 1 trial, which is assessing safety, pharmacokinetics, and preliminary efficacy, now has 6 dose-expansion cohorts: monotherapy in taxane-naive, radioligand therapy-naive, and radioligand therapy-exposed mCRPC, and combinations with enzalutamide (Xtandi) or docetaxel in early-line mCRPC and with darolutamide (Nubeqa) in metastatic hormone-sensitive prostate cancer (mHSPC).

“People living with advanced prostate cancer need new treatment options that can offer meaningful and durable benefit,” Moitreyee Chatterjee-Kishore, executive vice president and head of Oncology Development, Astellas, stated in the news release. “This fast track designation reinforces the importance of advancing VIR-5500 with urgency, and we are committed to exploring its potential to make a meaningful difference for patients and their families.”

[²¹²Pb]PSV359 Brings FAP-Targeted Alpha Therapy to SFTs

SFT is a rare disease and options are limited for locally advanced unresectable or metastatic disease.² Early research showed that among 813 patients across 126 tumor types, SFT (n = 34) had the highest median FAP messenger RNA expression, and FAP protein was confirmed in 76% (29/38) of SFT biopsies in a separate cohort. In 19 patients, gallium Ga 68 FAPI-46 PET showed a median maximum standardized uptake value of 13.2 vs 3.2 with fluorine F 18 fludeoxyglucose PET and detected 94.5% vs 77.3% of lesions. In 11 patients treated with yttrium Y 90 FAPI-46, the disease control rate was 82% and median progression-free survival was 227 days.⁴

Early human imaging with PSV359 has shown strong tumor uptake and rapid renal clearance.² In lower-dose cohorts of the ongoing phase 1/2a study, [²¹²Pb]PSV359 produced no DLTs or discontinuations due to adverse events, and treatment-emergent adverse events were grade 1 or 2 only as of a December 24, 2025, data cutoff. Dosing in cohort 3 (6.0 mCi) began in May 2026.⁵

“FAP-α is a particularly compelling target because of its broad expression across solid tumors and within the tumor microenvironment, creating the potential for PSV359 to address a substantial patient population across multiple cancer types,” Markus Puhlmann, chief medical officer of Perspective Therapeutics, stated in a press release. “There are currently no approved therapies specifically targeting FAP-α, despite its association with aggressive cancers and tumor environments that can limit drug penetration and suppress immune activity. Imaging FAP-α expression before treatment allows us to pair patient selection with targeted alpha radiopharmaceutical therapy and pursue that broad opportunity with precision.”

PSV359 delivers lead 212 to FAP-expressing tissue; labeled with lead 203 or gallium 68 (PSV377), the same moiety identifies FAP-positive patients. FAP sits mainly on cancer-associated fibroblasts, is expressed directly by some sarcoma and mesothelioma cells, and is largely absent from healthy tissue. Higher expression is tied to poor prognosis in non-small cell lung, colorectal, pancreatic, gastric, head and neck, esophageal, and ovarian cancers and mesothelioma.²

The multicenter, open-label study (NCT06710756) enrolls patients with advanced solid tumors confirmed FAP-positive by [²⁰³Pb]PSV359 imaging. Dose finding is evaluating safety and tolerability to set the recommended phase 2 dose, and antitumor activity may become an additional primary end point in expansion.²

“Fast track designation for FAP-positive solitary fibrous tumors is an important step in advancing the broader PSV359 program and our strategy of engineering targeted radiopharmaceutical therapy based on the alpha-generating isotope 212Pb to optimize the therapeutic window in oncology,” Thijs Spoor, chief executive officer, perspective, stated in the news release. “We look forward to working with the FDA and the medical community to define an efficient development path for PSV359 in this rare and serious disease.”

REFERENCES

1. Vir Biotechnology announces PSMA-targeted PRO-XTEN dual-masked T-cell engager VIR-5500 received FDA fast track designation for the treatment of prostate cancer. News release. Vir Biotechnology, Inc. October 8, 2026. Accessed October 8, 2026. https://tinyurl.com/3pujyvmc

2. Perspective Therapeutics granted fast track designation for [212Pb]PSV359 for the treatment of adult patients with locally advanced unresectable and/or metastatic FAP-positive solitary fibrous tumors. News release. Perspective Therapeutics, Inc. October 8, 2026. Accessed October 8, 2026. https://tinyurl.com/yc69uca

3. Vir Biotechnology reports positive updated phase 1 results for PSMA-targeting, PRO-XTEN dual-masked T-cell engager VIR-5500 in patients with metastatic prostate cancer. News release. Vir Biotechnology, Inc. February 23, 2026. Accessed October 8, 2026. https://tinyurl.com/2vpsrhep

4. Hamacher R, Pabst KM, Cheung PF, et al. Fibroblast activation protein α-directed imaging and therapy of solitary fibrous tumor. J Nucl Med. 2024;65(2):252-257. doi:10.2967/jnumed.123.266411

5. Perspective Therapeutics to present data from all clinical programs at the 2026 ASCO Annual Meeting, including findings from [212Pb]VMT01 in melanoma. News release. Perspective Therapeutics, Inc. May 21, 2026. Accessed October 8, 2026. https://tinyurl.com/rsmy6rzs