mCRPC (Metastatic Castration-resistant Prostate Cancer)Phase 2ZENITHNCT07623460
Zanzalintinib Efficacy Post Pluvicto® in Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer
A Phase 2 study testing Zanzalintinib in people with mCRPC (Metastatic Castration-resistant Prostate Cancer), run by Stuthi Perimbeti.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- mCRPC (Metastatic Castration-resistant Prostate Cancer)
- What is being tested?
- Zanzalintinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Sep 2031
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Aspartate aminotransferase (AST) ≤ 3 × ULN
- Alanine aminotransferase (ALT) ≤ 3 × ULN
- Alkaline Phosphatase (ALP) ≤ 3 × ULN; ≤ 5x ULN for subjects with documented bone metastasis; ≤ 10 x ULN for subjects with CRPC and bone metastasis if predominantly bone-specific ALP
- International Normalized Ratio (INR) ≤ 1.5 x upper limit of normal (ULN)
- Activated Partial Thromboplastin Time (aPTT) ≤ 1.2 x upper limit of normal (ULN)
- Males able to father a child who are sexually active with female of childbearing potential and their partners must be willing to abstain from heterosexual activity or to use an effective method(s) of contraception as outlined in Section 5.3.
- Ability of the subject to understand and comply with study procedures for the entire length of the study, as determined by the enrolling physician or protocol designee.
Who cannot join
- 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.
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- 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:
- 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).
- Uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic or > 90 mm Hg diastolic despite optimal antihypertensive treatment.
- Stroke (including transient ischemia attack [TIA]), myocardial infection, or other clinically significant arterial thrombotic and/or ischemic event within 6 months before the first dose of study treatment.
- Pulmonary embolism (PE) or deep vein thrombosis (DVT) or prior clinically significant venous events within 3 months before the first dose of study treatment.
- NOTE: Subjects with a diagnosis of DVT within 6 months are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 1 week before the first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen.
- NOTE: Subjects who do not require prior anticoagulation therapy may be eligible but must be discussed and approved by the sponsor-investigator.
- Gastrointestinal (GI) disorders including those associated with a high risk of perforation or fistula formation: i. Tumor invading the GI tract from external viscera. ii. Active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, or acute pancreatitis.
- Acute obstruction of the bowel, gastric outlet, or pancreatic or biliary duct within 6 months before the first dose unless cause of obstruction is definitively managed and subject is asymptomatic.
- Abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before the first dose. NOTE: Complete healing of an intra-abdominal abscess must be confirmed before the first dose of study treatment.
- Known gastric or esophageal varices. vi. Ascites, plural effusion, or pericardial fluid requiring drainage in the last 28 days.
- Clinically significant hematuria, hematemesis, or hemoptysis of > 0.5 teaspoon (2.5 mL) of red blood, or other history of significant bleeding (e.g. pulmonary hemorrhage) within 84 days (12 weeks) before the first dose of study treatment.
- Symptomatic cavitating pulmonary lesion(s) or endobronchial disease (asymptomatic or radiated lesions allowed).
- Lesions invading major blood vessel including, but not limited to, inferior vena cava, pulmonary artery, or aorta. NOTE: Subjects with intravascular tumor extension (eg. Tumor thrombus in renal vein or inferior V. cava) may be eligible following sponsor-investigator approval.
- Other clinically significant disorders that would preclude safe study participation.
- Active infection requiring systemic therapy. NOTE: Subjects receiving prophylactic antimicrobial treatments (antibiotics, antimycotic, antiviral) are eligible for the study.
- Known infection with acute or chronic hepatitis B or C, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness. NOTE: Subjects with HIV/AIDS may be eligible if they meet all of the following criteria:
- On stable anti-retroviral therapy ii. CD4+ T cell count ≥ 200/µL iii. Undetectable viral load NOTE: To be eligible, participants taking CYP inhibitors (eg. zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 28 days (4 weeks) prior to the first dose. CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider.
- Serious non-healing wound/ulcer/bone fracture. NOTE: non-healing wounds or ulcers are permitted if due to tumor-associated skin lesions.
- Malabsorption syndrome. e. Pharmacologically uncompensated, symptomatic hypothyroidism. f. Moderate to severe hepatic impairment (Child-Pugh B or C). g. Requirement for hemodialysis or peritoneal dialysis. h. History of solid organ or allogenic stem cell transplant.
- Major surgery (eg. GI surgery, removal or biopsy of brain metastasis) within 56 days (8 weeks) prior to the first dose of treatment. Minor surgery (eg. simple excision, tooth extraction) within 5 days before the first dose of study treatment. Complete wound healing from major or minor surgery must have occurred at least prior to the first dose of study treatment.
- NOTE: Fresh tumor biopsies should be performed at least 5 days before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior surgical procedures, including biopsies, are not eligible.
- Corrected QT interval calculated by the Fridericia formula (QTcF) > 480 ms within 14 days per electrocardiogram (ECG) before first dose of study treatment.
- NOTE: Triplicate ECG evaluations will be performed and the average of these 3 consecutive results for QTcF will be used to determine eligibility.
- Inability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube.
- Other conditions, which in the opinion of the investigator, would compromise the safety of the patient or the patient's ability to complete the study.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: ZENITH: Zanzalintinib Efficacy Post Pluvicto® in Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer
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.
- Being tested
- Zanzalintinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZanzalintinibDrug
Also called XL092
60mg orally (PO) once daily until evidence of radiographic progression, intolerable adverse events, or withdrawal of consent.
| Study group | Role | What they receive |
|---|---|---|
| Zanzalintinib | Experimental | 60mg orally (PO) once daily Receives: Drug: Zanzalintinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (3)
PSA Response
PSA response defined as a ≥50% decline in PSA from baseline (measured twice at least 3 weeks apart) using PCWG3 criteria.
Measured: 3 years
Objective response rate
ORR will be defined as the proportion of CR+PR using PCWG3 criteria for subjects with measurable disease
Measured: 3 years
Adverse events
Adverse events as determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2026
- Study startNov 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for mCRPC (Metastatic Castration-resistant Prostate Cancer)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stuthi Perimbeti
- Sponsor type
- University, hospital or other
- Collaborators
- Exelixis, Penn State Cancer Institute
- Responsible party
- Sponsor-investigator, Stuthi Perimbeti, Hoosier Cancer Research Network
- Investigators
- Stuthi Perimbeti, MD, MPH, Principal investigator, Penn State Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07623460
- Sponsor's protocol ID
- BTCRC-GU24-692
- Acronym
- ZENITH
- Status last verified
- Nov 2026
- First submitted
- 29 May 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ZENITH: Zanzalintinib Efficacy Post Pluvicto® in Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer
- ClinicalTrials.gov ID
- NCT07623460
- Acronym / sponsor ID
- ZENITH / BTCRC-GU24-692
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Stuthi PerimbetiUniversity, hospital or other
- Collaborators
- Exelixis, Penn State Cancer Institute
- Study start
- Nov 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2031 (estimated)
- First posted
- 3 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zanzalintinib | Experimental | Drug: Zanzalintinib60mg orally (PO) once daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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.
Key exclusion criteria (38 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZanzalintinibAlso: XL09260mg orally (PO) once daily until evidence of radiographic progression, intolerable adverse events, or withdrawal of consent. | Drug | Zanzalintinib |
Primary outcome
Radiographic progression free survival (rPFS)
Time frame: 3 years
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 secondary outcomes
PSA Response
Time frame: 3 years
Objective response rate
Time frame: 3 years
Adverse events
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
Related trials for mCRPC (Metastatic Castration-resistant Prostate Cancer)
Not yet recruitingPhase 1/2
STAR0602 With Nivolumab in Non Small Cell Lung Cancer and in Metastatic Castrate-Resistant Prostate Cancer, and STAR0602 Alone in Thymic Carcinoma
NSCLC, Non-Small Cell Lung Cancer
RecruitingObservational study
ARCTIC: Liquid Biomarkers in the Prospective Androgen Receptor Signaling Inhibitors (ARSI) Resistance Clinical Trials
Prostate Cancer, Prostate Adenocarcinoma
Active, not recruitingPhase 2
FPI-2265 (225Ac-PSMA-I&T) and Olaparib for Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Metastatic Castration-resistant Prostate Cancer
Active, not recruitingPhase 3
Talazoparib + Enzalutamide vs. Enzalutamide Monotherapy in mCRPC
mCRPC
RecruitingPhase 3
Study of Opevesostat (MK-5684) Versus Alternative NHA in mCRPC (MK-5684-003)
Prostate Cancer Metastatic
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Stuthi Perimbeti, MD, MPH principal investigator
Penn State Cancer Institute
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Zanzalintinib in people with mCRPC (Metastatic Castration-resistant Prostate Cancer), run by Stuthi Perimbeti.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Stuthi Perimbeti, MD, MPH (717-531-4800, sperimbeti@pennstatehealth.psu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Radiographic progression free survival (rPFS) (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.