This is a phase 2a, open label, single arm, multi-site study of xaluritamig in mCRPC patients following treatment with ≥1 ARPI, taxane chemotherapy (if eligible) and stable or partial PSA response following 2 cycles of lutetium 177 vipivotide tetraxetan.
Participants will continue treatment until clinical or radiographic progression of disease, withdrawal, or toxicity requiring discontinuation of therapy. All participants will be evaluated for overall response per RECIST v1.1,8 radiographic progression free survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) criteria, and PSA response. Approximately 30 participants will be enrolled. There is no data on response with alternative treatments following lutetium 177 vipivotide tetraxetan against which to benchmark the response rate. This phase 2a study will serve as an exploratory pilot to determine if a larger phase 2b study is warranted in this setting.
18 years of age and above
Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (<50 ng/dL or <1.7 nmol/L).
Received ≥1 novel ARPI (e.g., enzalutamide, darolutamide, apalutamide and/or abiraterone).
Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments in the judgment of the site Principal Investigator (PI). Participants with prior history of malignancy that have been adequately treated and who have been disease-free for > 3 years are eligible, as are subjects with adequately treated non-melanoma skin cancer or superficial bladder cancer.
Requirement for chronic systemic corticosteroid therapy (prednisone dose >10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-TNFα therapies) unless stopped (with adequate tapering) within 7 days prior to dosing. Corticosteroid treatment for adverse event management as described in Section 6.1.10 is allowed.
Previous PSMA-targeted radioligand therapy, aside from treatment with 2 cycles of lutetium 177 vipivotide tetraxetan, is not allowed.
Prior PSMA radioligand therapy within 6 weeks of first dose of study treatment.
Single group
Xaluritamig
Drugshort-term IV infusion
Proportion of Participants who achieve Partial or Complete Response or PSA90
Proportion of participants with mCRPC treated with xaluritamig after lutetium-177 vipivotide tetraxetan who achieve either: (1) a confirmed Complete Response (CR) or Partial Response (PR) within 24 weeks by local investigator assessment per RECIST v1.1 in participants with baseline measurable disease, with confirmation ≥4 weeks after initial response; or (2) a confirmed PSA90 response, defined as a ≥90% decline from baseline PSA in participants with baseline PSA ≥2.0 ng/mL within 24 weeks, confirmed by a subsequent PSA assessment obtained ≥2 weeks later. RECIST v1.1 classifies tumor response as CR (disappearance of all target lesions), PR (≥30% decrease in tumor size), Stable Disease (SD), or Progressive Disease (PD; ≥20% increase in tumor size or new lesions). Higher response rates indicate greater treatment efficacy.
Radiographic Progression-Free Survival (rPFS)
Time from initiation of study treatment to the earliest occurrence of radiographic disease progression per RECIST v1.1 or death from any cause, whichever occurs first. rPFS will be summarized as median time-to-event with a 90% confidence interval using the Kaplan-Meier method. Progression is determined using RECIST v1.1 and PCWG3 guidelines. New lesions require confirmation on a subsequent scan, with at least two initially identified new lesions remaining present. PCWG3 assesses progression in metastatic castration-resistant prostate cancer using RECIST v1.1 for soft tissue disease, bone scan criteria (including the "2+2" rule for new lesions), and PSA changes. RECIST v1.1 classifies response as Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD). Longer rPFS indicates better disease control; shorter rPFS indicates faster progression or treatment failure.
Duration of response (DOR)
Duration of response will be evaluated for participants and is defined as the time from the first evidence of CR/PR per the Investigator to the first evidence of disease progression (assessed in soft tissue per RECIST v1.1), or death, whichever occurs first. Will be reported as median time-to-event and 90% confidence interval according to the Kaplan Meier product-limit method. RECIST 1.1 (Response Evaluation Criteria in Solid Tumors) is a system for evaluating tumor response to treatment using four categories: Complete Response (CR) for disappearance of all target lesions, Partial Response (PR) for at least a 30% decrease in tumor size, Stable Disease (SD) for no significant change, and Progressive Disease (PD) for at least a 20% increase or new lesions. Minimum measurable size is 10 mm for solid tumors and 15 mm for lymph nodes. Better outcomes correspond to CR or PR, while PD indicates worsening.
Time to Prostate-Specific Antigen (PSA) response (30%, 50%, 70%, and 90%)
Defined as time to PSA decline of ≥ 30%, 50%, 70%, and 90% from start of study treatment. Median time to a decrease in PSA of 30%, 50%, 70%, and 90% from treatment initiation confirmed by a subsequent PSA value obtained ≥3 weeks later. Will be reported as median time-to-event and 90% confidence interval according to the Kaplan Meier product-limit method.
Time to Prostate-Specific Antigen (PSA) Progression
Time from treatment initiation to the date of first PSA value demonstrating progression confirmed by a subsequent PSA value obtained ≥3 weeks later. Will be reported as median time-to-event and 90% confidence interval according to the Kaplan Meier product-limit method.
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Thomas Jefferson University
Lead sponsor
Prostate Cancer Clinical Trials Consortium
Collaborator
Amgen
Collaborator
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