Zanzalintinib in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer

NCT06795009 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 202503049P50CA265793
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine the recommended Phase 2 dose of zanzalintinib when given in combination with paclitaxel in patients with recurrent high-grade uterine cancer. Other objectives include overall safety and tolerability as well as rates of response.

Conditions

Uterine Cancer; Endometrial Cancer

Keywords

Recurrent endometrial cancer; AXL/GAS6; p53 mutation; High risk

Outcome Measures

Primary Outcomes (1)

• Recommended Phase 2 dose (RP2D)

  Through completion of first cycle (each cycle is 21 days) of all enrolled patients (estimated to be 48 months and 3 weeks)

Secondary Outcomes (4)

• Frequency and severity of treatment-emergent adverse events

  From start of treatment through 30 days after last dose of zanzalinitinib (estimated to be 7 months)

• Overall response rate (ORR)

  After 3 cycles of treatment (each cycle is 21 days - estimated to be 63 days)

• Progression-free survival (PFS)

  From start of treatment through completion of follow-up (estimated to be 5.5 years)

• Overall survival (OS)

  From start of treatment through completion of follow-up (estimated to be 5.5 years)

Study Arms (3)

Dose Level 2 (Starting Dose): Zanzalintinib + Paclitaxel

EXPERIMENTAL

Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression.

Drug: Zanzalintinib; Drug: Paclitaxel

Dose Level 3: Zanzalintinib + Paclitaxel

EXPERIMENTAL

Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression.

Drug: Zanzalintinib; Drug: Paclitaxel

Dose Level 1 (Reduction): Zanzalintinib + Paclitaxel

EXPERIMENTAL

Patients will initiate paclitaxel on a 21-day cycle with the addition of zanzalintinib given on the same schedule. Dosing of zanzalintinib is dictated by the dose escalation schema. After 3 cycles, patients will be assessed for disease response. Patients who have progression will not continue on treatment. Patients who have a partial or complete response or stable disease will continue on treatment for another 3 cycles of paclitaxel + zanzalintinib at the assigned dose. Patients will be assessed for response again at the end of 6 cycles and may continue on treatment if they have partial response or stable disease. Up to 9 cycles of treatment with paclitaxel + zanzalintinib may be given. At the end of the 9 cycles, patients with a SD or PR can continue on maintenance zanzalintinib until progression. Patients with complete response after cycle 6 or 9 will continue single agent zanzalintinib as maintenance therapy until progression.

Drug: Zanzalintinib; Drug: Paclitaxel

Interventions

Zanzalintinib DRUG

Taken by mouth.

Also known as: XL092

Dose Level 1 (Reduction): Zanzalintinib + Paclitaxel; Dose Level 2 (Starting Dose): Zanzalintinib + Paclitaxel; Dose Level 3: Zanzalintinib + Paclitaxel

Paclitaxel DRUG

175 mg\^m2 intravenous over 3 hours.

Also known as: Taxol

Dose Level 1 (Reduction): Zanzalintinib + Paclitaxel; Dose Level 2 (Starting Dose): Zanzalintinib + Paclitaxel; Dose Level 3: Zanzalintinib + Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Diagnosis of recurrent, FIGO grade 3 endometrioid, serous, or mixed high grade uterine or endometrial cancer or uterine carcinosarcoma. Patients must have experienced either prior progression on a platinum-based therapy or intolerance to platinum. Patients with dMMR or MSI-H tumors or targetable HER2 alterations are required to have received prior therapy with appropriate targeted agents.
• prior lines of anti-cancer therapy are allowed.
• Subjects who have received prior treatment with trastuzumab, pembrolizumab, or dostarlimab can enroll in the study. Use of these agents together or as maintenance therapy is considered 1 regimen.
• Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy are permitted)
• Patients must have disease that cannot be managed by local therapy targeted at the tumor site (i.e. surgery, radiation therapy).
• Measurable disease by RECIST 1.1.
• At least 18 years of age.
• ECOG performance status ≤ 2.
• Adequate bone marrow and organ function within 14 days prior to first dose of study treatment, as defined below:
• Absolute neutrophil count ≥ 1.5 K/cumm without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection.
• Platelets ≥ 100 K/cumm ) without transfusion within 2 weeks of screening laboratory sample collection.
• Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks prior to screening laboratory sample collection.
• Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3 x ULN).
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN. For subjects with documented bone metastasis ALP ≤ 5 x ULN. Serum creatinine \< 1.5 x ULN OR calculated or measured creatinine clearance ≥ 40 mL/min (using Cockcroft-Gault equation)
• INR ≤ 1.5 x IULN

You may not qualify if:

• Any prior treatment with zanzalintinib
• A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment, or any prior treatment with any tyrosine kinase inhibitor (TKI) or any prior treatment with bevacizumab.
• Receipt of any other (non-study) cytotoxic chemotherapy, radiation, targeted treatment, or immunotherapy (including investigational) within 4 weeks prior of start of study treatment.
• Receipt of any other investigational agents or has received an investigational agent within 4 weeks of start of study treatment.
• Radiation therapy for bone metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before first dose of study treatment. 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 treatment. 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).
• Allowed anticoagulants are the following:
• 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 treatment 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 first dose of study treatment, whichever is longer.
• Any complementary medications (eg, herbal supplements or traditional Chinese medicines) to treat the disease under study within 2 weeks before first dose of study treatment.
• The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
• Unstable or deteriorating cardiovascular disorders:
• 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).

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Cancer Institute (NCI): collaborator
• Exelixis: collaborator

Study Sites (4)

University of California, San Francisco

San Francisco, California, 94143, United States

NOT YET RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

University of New Mexico

Albuquerque, New Mexico, 87106, United States

NOT YET RECRUITING

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

NOT YET RECRUITING

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Uterine Neoplasms; Endometrial Neoplasms

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• David G Mutch, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David G Mutch, M.D.

CONTACT

314-362-3181; mutchd@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2025
• First Posted: January 27, 2025
• Study Start: October 17, 2025
• Primary Completion (Estimated): November 30, 2029
• Study Completion (Estimated): April 30, 2035
• Last Updated: December 11, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)