Zanzalintinib in Men With Aggressive Variant Prostate Cancer

NCT07218666 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN-GU23-655
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multi-center single arm phase II study to evaluate the antitumor activity of zanzalintinib 60mg orally (PO) once daily in subjects with AVPC. Zanzalintinib may continue until radiographic progression (or beyond), intolerable adverse events, or withdrawal of consent. As long as the subject is clinically stable, subjects may receive study treatment even after radiographic progression, until they are no longer clinically benefiting from the study treatment in the opinion of the treating Investigator, or they need subsequent systemic anticancer treatment or other urgent tumor directed medical intervention to prevent life-threatening complications. This study will use a 2-stage group-sequential design for enrollment. The first stage will consist of enrolling 15 subjects. No more than 5 of the first 15 subjects can have received chemotherapy in the castrate- resistant setting.

Conditions

Aggressive Variant Prostate Carcinoma

Outcome Measures

Primary Outcomes (2)

• Radiographic progression free survival (rPFS)

  For soft tissue lesions, rPFS is defined as the date of Cycle 1 Day 1 to date of radiologic progression of soft tissue lesions per RECIST 1.1 or death whichever occurs first.

  6 months

• Radiographic progression free survival (rPFS)

  For bone lesions, rPFS is defined as the date of Cycle 1 Day 1 to date of progression of bone lesions per PCWG3 criteria or death whichever occurs first.

  6 months

Secondary Outcomes (6)

• Adverse Events

  4 years

• Overall Survival

  4 years

• Objective response rate (ORR)

  4 years

• Duration of response (DoR)

  4 years

• Quality of life (QOL)

  4 years

Study Arms (1)

Zanzalintinib

EXPERIMENTAL

Zanzalintinib 60mg orally (PO) will be given once daily in subjects with AVPC.

Drug: Zanzalintinib

Interventions

Zanzalintinib DRUG

Zanzalintinib 60mg orally (PO) once daily in

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 prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 within 14 days prior to registration.
• Histological or cytologically proven prostate cancer
• Must have had evidence of metastatic disease (AJCC v.8 M1 disease) based on conventional CT/MRI and/or bone scan. This will be defined as:
• Bone metastases detected by CT, radionuclide 99Tc- methylene bisphosphonate bone scan, or MRI as defined by PCWG3 criteria, OR
• Non-pelvic lymph node metastases (measurable lymph nodes above the aortic bifurcation; lymph nodes are measurable if the short axis diameter is ≥15 mm) detected on CT or MRI as defined by RECIST version 1.1. Subjects with regional lymph node metastases only (N1, below the aortic bifurcation) will not be eligible for the study; OR
• Visceral or soft tissue metastases detected on CT or MRI as defined by RECIST version 1.1. Soft tissue/visceral lesions are measurable if the long axis diameter is ≥10 mm.
• Bilateral orchiectomy or ongoing androgen deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist/antagonist (surgical or medical castration), with serum testosterone \< 50 ng/ dL (\< 1.73 nmol/L) at screening.
• Must have progressed during or after at least one second-generation androgen receptor pathway inhibitor (abiraterone acetate, enzalutamide, apalutamide, darolutamide) given for castration-sensitive locally advanced (T3 or T4) or metastatic castration-sensitive prostate cancer (CSPC), M0 castrate- resistant prostate cancer (CRPC), or metastatic CRPC.
• Note: Subjects may have previously received taxane-based chemotherapy for metastatic castration-sensitive prostate cancer (mCSPC), and sipuleucel-T, olaparib, Pluvicto (Lutetium (177Lu) vipivotide tetraxetan), and/or radium-223 for castrate -resistant prostate cancer. The number of patients who have received both taxanes and/or platinum in a CRPC setting will be limited to 5/15 in the first stage and thereby sponsor investigator approval is required prior to enrollment of patients who meet above criteria.
• Presence of at least one of the following:
• Presence of visceral metastases or high-volume disease (\> 4 sites of metastases) on conventional imaging (CT/MRI/bone scan) with a PSA ≤ 5.
• Predominantly lytic bone metastasis.
• Bulky (≥5 cm) lymphadenopathy OR bulky (≥5 cm) high-grade (Gleason ≥8) tumor mass in the prostate/pelvis.

You may not qualify if:

• Pure small cell carcinoma of the prostate.
• Prior treatment with zanzalintinib.
• Imminent or established spinal cord compression based on clinical and/or imaging findings.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study drug.
• Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 2 weeks of start of investigational agent and during the study. Concomitant use of megestrol acetate or leuprolide is permitted. The anti-androgen abiraterone is permitted up to 1 week prior to the first dose of study drug. Other types of hormonal therapies with similar use require prior approval of the Sponsor Investigator.
• Radiation therapy for bone metastasis within 2 weeks or any other radiation therapy within 4 weeks before first dose of study drug. Systemic treatment with radionuclides within 6 weeks before first dose of study drug are not permitted. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible.
• Known brain metastases or cranial epidural disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) and stable for at least 4 weeks before first dose of study drug. Note: Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of enrollment. Note: Base of skull lesions without definitive evidence of dural or brain parenchymal involvement are allowed.
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors) and platelet inhibitors (eg, clopidogrel). Note: Subjects must discontinue prohibited oral anticoagulants within 3 days or 5 half-lives prior to first dose of study drug, whichever is longer.
• The following anticoagulants are allowed:
• 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, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study drug without clinically significant hemorrhagic complications from the anticoagulation regimen.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study drug.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• a. Unstable deteriorating cardiovascular disorders: i. Congestive heart failure New York Heart Association 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

• Deepak Kilari: lead
• Exelixis: collaborator
• Medical College of Wisconsin: collaborator

Study Officials

• Deepak Kilari, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Deepak Kilari, MD

CONTACT

414-805-3666; dkilari@mcw.edu

Allison Lipps

CONTACT

317-634-5842; alipps@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: October 16, 2025
• First Posted: October 20, 2025
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 21, 2025

Record last verified: 2025-10