Zanzalintinib for Advanced Urothelial Carcinoma Progressing After Prior Therapy

NCT07185945 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU23-633
• Study Type: interventional
• Target: 44
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase II, single arm study. All subjects will receive Zanzalintinib 60 mg orally once daily until progression per RECIST 1.1 or intolerable toxicities or patient/investigator decision to discontinue study therapy. Radiology imaging will be performed every 8 weeks for 3 timepoints then every 12 weeks thereafter. A window of ± 7 days may be applied to all study visits to accommodate observed holidays, inclement weather, scheduling conflicts etc.

Conditions

Advanced Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR is defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST1.1.

  24 months

Secondary Outcomes (4)

• Progression-free survival (PFS)

  24 months

• Duration of Response (DOR)

  24 months

• Overall survival (OS)

  24 months

• Number of Participants with Adverse Events

  24 months

Study Arms (1)

Zanzalintinib

EXPERIMENTAL

All subjects will receive Zanzalintinib 60 mg orally once daily until progression per RECIST 1.1 or intolerable toxicities or patient/investigator decision to discontinue study therapy.

Drug: Zanzalintinib

Interventions

Zanzalintinib DRUG

60 mg orally once daily

Zanzalintinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• 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 ≤ 2 within 28 days prior to registration.
• Histologically confirmed predominant urothelial carcinoma (T4b, N0, M0; any T, N1-N3, M0; any T, any N, M1). American Joint Committee on Cancer (AJCC) v8 staging manual. NOTE: must be locally advanced unresectable or metastatic.
• Measurable disease according to RECIST 1.1 within 28 days prior to registration.
• Progressive disease by RECIST 1.1 following 1 to 3 lines of prior therapy. NOTE: prior lines of therapy must include Enfortumab Vedotin (EV) \[unless ineligible for EV\] and PD(L)1 inhibitor \[unless ineligible for PD(L)1 inhibitor\]. Prior platinum-based chemotherapy and other agents are allowed but not required.
• Prior cancer treatment must be completed ≥ 28 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen to Grade ≤ 1 or baseline. NOTE: Alopecia and sensory neuropathy of Grade ≤ 2 are acceptable.
• Demonstrate adequate organ function as defined in the table below. All screening labs to be obtained within 14 days prior to registration.
• Absolute Neutrophil Count (ANC) ≥ 1,500/mm3
• Platelets (Plt) ≥ 100,000/mm3 (without transfusion within 14 days of screening laboratory sample collection)
• Hemoglobin (Hgb) ≥ 8 g/dL (without transfusion within 14 days of screening laboratory sample collection)
• Calculated creatinine clearance1 ≥ 40 mL/min
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3.0 × ULN for patients with Gilbert's disease
• Aspartate aminotransferase (AST) ≤ 3 × ULN or ≤ 5 x ULN with liver metastases
• Alanine aminotransferase (ALT) ≤ 3 × ULN or ≤ 5 x ULN with liver metastases

You may not qualify if:

• More than 3 lines of prior therapy (prior cisplatin-based perioperative chemotherapy within 1 year prior to subsequent therapy or registration, whichever comes first) and/or prior perioperative PD1 inhibitor within 12 weeks prior to subsequent therapy (or registration, whichever comes first) is considered a line of therapy).
• Prior receipt of a VEGF inhibitor.
• Prior receipt of zanzalintinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 28 days before registration.
• Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational therapy) within 28 days prior to Cycle 1 Day 1.
• Concomitant anticoagulation with oral anticoagulants (eg, warfarin, direct thrombin inhibitors ) and platelet inhibitors (eg, clopidogrel) are allowed only if:
• 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 7 days before registration without clinically significant hemorrhagic complications from the anticoagulation regimen.
• NOTE: Subjects must have discontinued oral anticoagulants within 3 days or 5 half-lives prior to registration, whichever is longer.
• Administration of a live, attenuated vaccine within 30 days before Cycle 1 Day 1.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 14 days before registration.
• Pharmacologically uncompensated, symptomatic hypothyroidism
• Current symptomatic central nervous system (CNS) metastases. NOTE: Patients with previously diagnosed CNS metastases are eligible if they have completed treatment and recovered from the acute effects of radiation therapy or surgery prior to registration, have tapered corticosteroid treatment to 10 mg/day or less and are neurologically stable.
• Deep vein thrombosis or pulmonary embolism or prior clinically significant venous events per investigator discretion within 12 weeks prior to registration. NOTE: Subjects with a diagnosis of deep vein thrombosis (DVT) beyond 1 month earlier are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 7 days prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen. Subjects with a diagnosis of DVT within 24 weeks are allowed if asymptomatic and stable at screening and are on a stable dose of the anticoagulant for at least 7 days prior to registration without clinically significant hemorrhagic complications from the anticoagulation regimen.
• Unstable or deteriorating cardiovascular disorders:

Sponsors & Collaborators

• Guru Sonpavde: lead
• Exelixis: collaborator
• Advent Health: collaborator

Study Officials

• Guru Sonpavde, MD

  Advent Health Orlando

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Guru Sonpavde, MD

CONTACT

407-303-2038; guru.sonpavde.md@adventhealth.com

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: September 15, 2025
• First Posted: September 22, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): March 1, 2029
• Last Updated: December 23, 2025

Record last verified: 2025-12