A Phase 3, Open-label, Multicenter, Randomized Study of Xaluritamig vs Cabazitaxel or Second Androgen Receptor-Directed Therapy in Subjects With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Chemotherapy
Study of Investigational Medication vs Standard Treatments in Cancer That Has Spread
Nabil Adra, MD
Primary Investigator
Brief description of study
The main objective of the study is to compare overall survival in participants receiving xaluritamig versus investigator's choice (cabazitaxel or second androgen receptor-directed therapy [ARDT]).
Primary: To compare overall survival (OS) in subjects receiving xaluritamig vs investigator s choice (cabazitaxel or second androgen receptor-directed therapy [ARDT])
Key secondary: To compare radiographic progression-free survival (rPFS) in subjects receiving xaluritamig vs investigator's choice (cabazitaxel or second ARDT)
Secondary: To evaluate other measures of efficacy of xaluritamig vs investigator s choice (cabazitaxel or second ARDT)
Detailed description of study
This is a randomized, multi-center, open-label, phase 3 study to evaluate the efficacy
and safety of xaluritamig versus investigator’s choice of cabazitaxel or second ARDT in
subjects with mCRPC previously treated with taxane chemotherapy.
Eligible subjects will be randomized with a 2:1 allocation ratio to receive either:
xaluritamig monotherapy (experimental arm) or investigator’s choice of cabazitaxel or
second ARDT (control arm).
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Metastatic Castration-resistant Prostate Cancer
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Age: 18 years - 100 years
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Gender: Male
Inclusion Criteria:
- Participant has provided informed consent prior to initiation of any study-specific activities/procedures.
- Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent.
- Participant must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
- mCRPC with ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging obtained within 28 days prior to enrollment.
- Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
- Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL.
- Soft-tissue progression defined as an increase ≥ 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
- Progression of bone disease: evaluable disease or new bone lesion(s) by bone scan (2+2 PCWG3 criteria, Scher et al, 2016).
- Participants must have had a prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L).
- Prior treatment with at least one ARDT.
- Prior treatment with one taxane therapy. Prior treatment with docetaxel in the hormone-sensitive setting is permitted. Participants who received two or more prior chemotherapy regimens in the castrate-resistant setting are not eligible.
- Prior treatment with radioligand therapy (RLT), radionuclide therapy (Radium-223), poly ADP-ribose polymerase (PARP) inhibitor, or immune checkpoint inhibitor is permitted.
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
- Adequate organ function.
Key Exclusion Criteria:
Prior & Concomitant Therapy:
- Prior six transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted therapy.
- Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks prior to the first dose of study treatment, not including androgen suppression therapy.
- Prior Prostate-Specific Membrane Antigen (PSMA) radioligand therapy (RLT) within 2 months of the first dose of study treatment unless participants received < 2 cycles of therapy. Participants who received 1 cycle of PSMA RLT within 35 days prior to the first dose of study treatment are also excluded.
- Participants who started a bisphosphonate or denosumab regimen within 4 weeks prior to the first dose of study treatment.
- Radiation therapy within 4 weeks prior to the first dose of study treatment (or local or focal radiotherapy within 2 weeks prior to the first dose of study treatment).
- Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy.
Disease Related:
- Participants with a history of central nervous system (CNS) metastasis.
- Unresolved toxicities from prior anti-tumor therapy with CTCAE version 5.0 events grade above 1 or baseline, with the exception of alopecia or toxicities that are stable and well controlled AND there is an agreement to allow inclusion by both the investigator and the sponsor.
This study investigates the treatment of metastatic castration-resistant prostate cancer (mCRPC), which is a type of cancer that continues to grow even when the amount of testosterone in the body is reduced to very low levels. The purpose of this study is to compare overall survival between participants receiving an investigational medication and those receiving standard treatments such as cabazitaxel or a second androgen receptor-directed therapy (ARDT).
Participants will be randomly assigned to one of two study arms. One arm will receive the investigational medication, while the other arm will receive either cabazitaxel or a second ARDT as chosen by the investigator. The study will evaluate different measures of efficacy, including radiographic progression-free survival, which checks how long patients live without their cancer getting worse on scans.
- Who can participate: Adults aged 18 or older with metastatic prostate cancer that keeps growing despite low testosterone can join. They must have had chemotherapy before and show signs of cancer getting worse. Participants should also have adequate organ function and performance status.
- Study details: Participants will get either the investigational medicine or a standard treatment picked by their doctor. The study will see how long they live and other results in these groups.