Zanzalintinib Efficacy Post Pluvicto® in Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer

NCT07623460 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BTCRC-GU24-692
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-center single arm phase II study of zanzalintinib after Pluvicto in chemotherapy-naïve mCRPC. Subjects will receive zanzalintinib 60mg orally (PO) once daily. Zanzalintinib may continue until evidence of radiographic progression, intolerable adverse events, or withdrawal of consent. Two interim analyses will be performed; a safety interim analysis to be performed for the first 5 evaluable subjects, and a futility interim analysis to be performed for the first 15 evaluable subjects.

Conditions

mCRPC (Metastatic Castration-resistant Prostate Cancer)

Outcome Measures

Primary Outcomes (1)

• Radiographic progression free survival (rPFS)

  rPFS is defined as the duration of time from Cycle 1 Day 1 to the date of radiographic progression per Prostate Cancer Working Group 3 (PCWG3) criteria or death due to any cause, whichever occurs first.

  3 years

Secondary Outcomes (3)

• PSA Response

  3 years

• Objective response rate

  3 years

• Adverse events

  3 years

Study Arms (1)

Zanzalintinib

EXPERIMENTAL

60mg orally (PO) once daily

Drug: Zanzalintinib

Interventions

Zanzalintinib DRUG

60mg orally (PO) once daily until evidence of radiographic progression, intolerable adverse events, or withdrawal of consent.

Also known as: XL092

Zanzalintinib

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of 0-2.
• Metastatic Castrate Resistant Prostate Cancer (mCRPC) with histologically/cytologically confirmed adenocarcinoma without small cell histology.
• Prior cancer treatment must be completed at least 14 days prior to registration NOTE: Antiandrogen agent, against LHRH axis, such as Leuprolide or institutional equivalent, Relugolix, Degarelix etc. are to be continued during the course of the treatment.
• Must have recovered from adverse effects of any prior oncologic treatment (e.g. prior surgery, radiotherapy, or other antineoplastic therapy). CTCAE adverse events ≤ grade 1 are acceptable. CTCAE adverse events grade 2 or greater may be acceptable as determined by the treating Investigator.
• Patients must have had at least one dose of prior Pluvicto therapy for prostate adenocarcinoma. Patients must have received PARP inhibitor if the tumor has BRCA 1 or 2 pathogenic mutations prior to enrolling on this study unless intolerant or contraindicated per treating investigator.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 14 days prior to registration.
• Platelets (Plt) ≥ 100,000 /mm3 without transfusion within 14 days of sample collection
• Absolute Neutrophil Count (ANC) ≥ 1.5 K/mm3 without granulocyte colony-stimulating factor support within 14 days of sample collection
• Hemoglobin (Hgb) ≥ 9g/dL without transfusion within 14 days of sample collection
• Serum Creatinine OR Calculated creatinine clearance (Cockcroft-Gault formula will be used to calculate creatinine clearance) ≤ 1.5 x ULN
• ≥ 40 mL/min (≥ 0.67 mL/sec)
• Urine protein OR Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine or 24-hour urine protein \<1.5 g.
• Total Bilirubin ≤ 1.5 × upper limit of normal (ULN) ≤ 3 × ULN for subjects with Gilbert's disease

You may not qualify if:

• Receipt of chemotherapy in the mCRPC disease state. NOTE: Prior exposure and any number of lines of chemo (including docetaxel) during hormone naïve or castrate sensitive state of the cancer is allowed.
• Any other active malignancy or diagnosis of another malignancy within 2 years before first dose of study treatment requiring systemic treatment, except for superficial skin cancers, or localized, low grade tumors deemed cured and not treated with systemic therapy.
• NOTE: Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial as approved by the Principal Investigator.
• Known central nervous system (CNS) metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 28 days before the first dose of study treatment.
• NOTE: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of registration. Base of skull lesions without definitive evidence of dural or brail parenchymal involvement are allowed.
• Treatment with any investigational drug within 14 days prior to registration.
• History of severe allergic anaphylactic reactions or hypersensitivity to zanzalintinib or any of their excipients such as Cabozantinib.
• Prior treatment with Zanzalintinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 14 days before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic (such as systemic Immune Checkpoint Inhibitors) or other systemic anticancer therapy (including investigational) within 28 days before the first dose of study treatment. NOTE: The antiandrogen abiraterone is permitted up to 7 days prior to the first dose of study treatment. Concomitant use of megestrol acetate or leuprolide/Relugolix/ Degarelix/ Equivalent drugs such as Eligard etc. per institutional guidelines is permitted. Other types of hormonal therapies with similar use require prior approval from the sponsor-investigator.
• Radiation therapy for bone metastasis within 14 days, any other radiation therapy within 28 days before the first dose of study treatment. Systemic treatment with radionuclides within 42 days before the first dose of study treatment.
• Active treatment with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct Xa inhibitor betrixaban or platelet inhibitors (e.g., clopidogrel) within 5 days of registration. Allowed anticoagulants include: prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH), therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, apixaban. Allowed also in patients with known brain metastases who are on a stable dose of the anticoagulant for at least 1 week prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor
• Uncontrolled, significant intercurrent or recent illness including, but not limited to the following conditions:
• a. Unstable or deteriorating cardiovascular disorders: i. Congestive heart failure New York Heart Association Class 3 or 4, class 2 or higher, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg. ventricular flutter, ventricular fibrillation, Torsades de pointes).
• ii. Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.

Sponsors & Collaborators

• Stuthi Perimbeti: lead
• Exelixis: collaborator
• Penn State Cancer Institute: collaborator

Study Officials

• Stuthi Perimbeti, MD, MPH

  Penn State Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stuthi Perimbeti, MD, MPH

CONTACT

717-531-4800; sperimbeti@pennstatehealth.psu.edu

Amber Ryba

CONTACT

317-634-5842; aryba@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: June 3, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): September 1, 2031
• Last Updated: June 3, 2026

Record last verified: 2026-05