Rubraca

Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy with Lutetium-177 (¹⁷⁷Lu-PSMA) is an established treatment for metastatic prostate cancer. Administered intravenously, it enables targeted irradiation of PSMA-expressing tumor cells. However, 30-50% of patients derive limited benefit. This variability could be partly explained by heterogeneity in delivered dose across lesions, leading to under-treatment of certain metastases. The addition of targeted external beam radiotherapy (EBRT) may compensate for this underdosing by delivering a precise dose to insufficiently irradiated lesions. We hypothesize that the addition of adaptive EBRT to ¹⁷⁷Lu-PSMA will reduce the incidence of skeletal-related events (pathologic fracture, spinal cord compression, surgery, or palliative radiotherapy) without increasing toxicity. Adaptive EBRT and RLT for mCRPC (ARREST) is a pragmatic registry-based phase 2, multi-center randomized controlled trial within the PERa prospective cohort (NCT03378856) planned to activate in 2026. Patients who are receiving SOC 177Lu-PSMA with targetable metastatic burden identified on imaging suitable for EBRT will be eligible. One hundred and twenty eligible patients will be randomized 1:1 to receive either SOC 177Lu-PSMA therapy alone (maximum 6 cycles) or to combined 177Lu-PSMA plus adaptive EBRT. Patients in the experimental arm will undergo FDG-PET at study entry and SPECT-CT after each cycle of radioligand therapy. Lesions selected for EBRT boost will be selected based on a set of criteria that include estimated suboptimal dose absorbed from 177LuPSMA, lesions demonstrating low PSMA but high FDG update, symptomatic lesions, and those at high risk for skeletal-related events. Selected lesions will receive single-fraction EBRT. Dose prescribed will range from 6-12 Gy with the ideal goal of a combined total biological effective dose of ≥50 Gy (α/β = 5) with priority to dose limits for organs at risk. A maximum treatment time of 60 minutes is permitted for each adaptive EBRT treatment. Patients in the experimental arm that achieve complete response measured by 177Lu-SPECT-CT and PSA will pause ARREST and resume at progression. The primary endpoint is skeletal related events at 1 year. Secondary objectives include overall survival, 177Lu-SPECT-CT and PSA response, toxicity, and quality of life. The sample size is designed to detect a 12 month improvement in the rate of skeletal related events with a HR 0.61, one-sided alpha of 0.1 and 80% power. ARREST is hypothesized to safely optimize tumor dose, offering a personalized hybrid approach that may lead to improved patient outcomes. In addition, this study will permit further understanding of these two distinct radiation delivery methods and their effect on tissues, thereby refining the relative biological effectiveness model for more precise treatment planning.

This study will evaluate the efficacy and safety of the combination of inavolisib plus enzalutamide compared with physician's choice of alternative androgen receptor pathway inhibitor (ARPi) or docetaxel in biomarker-selected participants with metastatic castrate-resistant prostate cancer (mCRPC) who have received one prior second-generation ARPi.

This is a multi-center, open-label Phase 1/2 trial evaluating the safety and efficacy of AB-3028 in subjects with metastatic castration resistant prostate cancer (mCRPC).

This Phase 1 study will evaluate the safety, tolerability, and preliminary effectiveness of AB001, an alpha-emitting radioligand targeting prostate-specific membrane antigen (PSMA), in patients with advanced prostate cancer who are either 177Lu-PSMA naïve or experienced. The study includes dose escalation to identify a recommended dose and dose expansion to further assess safety and anti-tumour activity. Primary objectives are to characterize the safety profile and determine the optimal dose and schedule for future studies

The purpose of this study is to evaluate the safety and tolerability of Lutetium-177-PSMA-617 (PLUVICTO) in patients with metastatic castration-resistant prostate cancer (mCRPC) and extensive bone metastases, which appear as a "super scan" pattern on a bone scan. Pluvicto is FDA-approved, but patients with super scan bone scans were previously excluded from the VISION clinical trial, leaving a knowledge gap. The study will enroll up to 30 men with metastatic castration-resistant prostate cancer, with an initial dosing approach that differs from the standard dose. The safety and tolerability of PLUVICTO will be evaluated in this study, with a focus on identifying the optimal dose for this population. This study addresses an important gap in understanding how Pluvicto performs in mCRPC patients with super scan findings.

The goal of this clinical trial is to assess if a personalized regime of 177Lu-PSMA-617 (Lutetium Lu 177 vipivotide tetraxetan, also known as Pluvicto) is feasible and safe in a population of patients with metastatic castrate-resistant prostate cancer (mCRPC). The main questions it aims to answer are: 1. Can the administered activity (cumulative or per-cycle) be increased in a majority of participants? 2. What is the incidence of some specific adverse reactions during the treatment? Researchers will compare participants receiving a personalized regime to participants receiving the standard fixed-activity regime of 177Lu-PSMA-617 to see if the activity can be safely increased through personalization based on renal dosimetry (i.e. the measure of how much radiation is actually delivered to the kidney). Participants will receive up to 6 treatments of 177Lu-PSMA-617 every 6 weeks and be regularly evaluated with imaging and laboratory tests, as well as with questionnaires.

The purpose of this study is to assess safety of combination of AAA617 (administered for 6 cycles at a dose of 7.4 GBq (200 mCi) +/- 10%) and ARPI and AAA617 alone in PSMA-positive mCRPC patients who were previously treated and progressed on ARPI in the biochemical recurrence (BCR)-non metastatic hormone sensitive prostate cancer (mHSPC), mHSPC, or non-metastatic Castration Resistant Prostate Cancer (nmCRPC) setting and have not previously received a taxane-containing regimen in the metastic castrate resistant prostate cancer (mCRPC) setting.

The main purpose of the study is to assess the safety and tolerability of AZD2284, AZD2287, and AZD2275.

This study will explore whether a combination of the investigational drug PF-06821497 and enzalutamide will work better than taking enzalutamide alone in participants with mCRPC who are ARSi or abiraterone naïve.

Pfizer MEVPRO-1 (C2321014) is a randomized, open-label, multi-center clinical trial evaluating whether combining the study medicine (PF-06821497) with enzalutamide is safe and effective compared to physician's choice of either second-line androgen receptor (AR) directed therapy with enzalutamide or docetaxel (chemotherapy) for treating metastatic castration-resistant prostate cancer (mCRPC) after progression on prior abiraterone acetate treatment. The primary objective of this clinical trial is to assess the radiographic progression free survival (rPFS) of the combination of PF-06821497 plus enzalutamide versus physician's choice of enzalutamide or docetaxel.

The purpose of the study is to assess and evaluate dosimetry, safety, and tolerability following administration of up to 12 cycles of (177Lu) vipivotide tetraxetan (also referred to as \[177Lu\]Lu-PSMA-617 or 177Lu-PSMA-617 and hereafter identified as AAA617) in taxane-naïve adult participants with PSMA-positive mCRPC who progressed on a prior ARPI treatment with normal renal function or mild renal impairment (eGFR ≥ 60ml/min).

Prostate cancer has the second highest incidence rate and is the fifth leading cause of cancer-related deaths among men worldwide. The purpose of this study is to assess safety, pharmacokinetics, and efficacy of ABBV-969 as a monotherapy. ABBV-969 is an investigational drug being developed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). There are parts to this study. Participants will receive ABBV-969 as a single agent at different doses. Approximately 140 adult participants will be enrolled in the study across sites worldwide. In part 1 (dose escalation), ABBV-969 will be intravenously infused in escalating doses as a monotherapy. In part 2, multiple doses will be selected from Part 1 and mCRPC participants will be assigned to one of these doses in a randomized fashion to determine the recommended Phase 2 dose. The estimated duration of the study is up to 3 years. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.