Zanzalintinib Combined With Eribulin in Advanced Liposarcoma and Leiomyosarcoma

NCT06957431 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202506154
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators hypothesize that the combination of eribulin and zanzalintinib will be tolerable and lead to improved progression-free survival (PFS) as compared to eribulin alone based on historical data.

Conditions

Advanced Leiomyosarcoma; Adipocytic Sarcoma; Advanced Liposarcoma

Keywords

Sarcoma; Eribulin; Tyrosine Kinase Inhibitor

Outcome Measures

Primary Outcomes (2)

• Number of adverse events experienced by participants

  Graded using CTCAE version 5.0.

  From start of treatment through 30 days after completion of treatment (estimated to be 25 months)

• Maximum tolerated dose (MTD)/recommended phase II dose (RP2D)

  The maximum tolerated dose (MTD) is defined as the dose level immediately below the dose level at which 2 patients of a cohort (of 2 to 6 patients) experience dose-limiting toxicity during the first cycle. Dose escalations will proceed until the MTD has been reached or, if the MTD is not reached, until 6 patients have been treated successfully at the highest dose level (which will then be termed the recommended phase II dose (RP2D)).

  Through cycle 1 of treatment (each cycle is 21 days)

Secondary Outcomes (4)

• Overall response rate (ORR) by RECIST 1.1

  Through completion of treatment (estimated to be 24 months)

• Progression-free survival (PFS)

  6 months from start of treatment

• Median Overall survival (OS)

  Through completion of follow-up (estimated to be 7 years)

• Kaplan-Meier Estimate of Overall survival (OS)

  24 months from start of treatment

Study Arms (3)

Dose Level 1 (starting dose): Zanzalintinib + Eribulin

EXPERIMENTAL

Patients will receive zanzalintinib 40 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle.

Drug: Zanzalintinib; Drug: Eribulin

Dose Level 2: Zanzalintinib + Eribulin

EXPERIMENTAL

Patients will receive zanzalintinib 60 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle.

Drug: Zanzalintinib; Drug: Eribulin

Dose Level -1: Zanzalintinib + Eribulin

EXPERIMENTAL

Patients will receive zanzalintinib 20 mg by mouth once daily on Days 1 through 21 and eribulin intravenously on Days 1 and 8 of a 21-day cycle.

Drug: Zanzalintinib; Drug: Eribulin

Interventions

Zanzalintinib DRUG

Supplied by Exelixis, Inc.

Also known as: XL092

Dose Level -1: Zanzalintinib + Eribulin; Dose Level 1 (starting dose): Zanzalintinib + Eribulin; Dose Level 2: Zanzalintinib + Eribulin

Eribulin DRUG

1.1 mg/m\^2 dose.

Also known as: Halaven

Dose Level -1: Zanzalintinib + Eribulin; Dose Level 1 (starting dose): Zanzalintinib + Eribulin; Dose Level 2: Zanzalintinib + Eribulin

Eligibility Criteria

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

You may qualify if:

• Pathologically proven diagnosis of unresectable or metastatic leiomyosarcoma or adipocytic sarcoma.
• Progressed on at least 1 line of prior therapy and have received no more than 4 lines of prior therapy.
• Measurable disease per RECIST 1.1.
• At least 18 years of age.
• ECOG performance status ≤ 1
• Adequate bone marrow and organ function within 14 days before 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 collection
• Platelets ≥ 100 K/cumm without transfusion within 2 weeks of collection
• Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks of collection
• INR ≤ 1.5 x ULN and aPTT ≤ 1.2 x ULN; for subjects on Factor Xa inhibitors, this criterion does not apply.
• Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease, ≤ 3.0 x IULN)
• AST(SGOT)/ALT(SGPT)/alkaline phosphatase (ALP) ≤ 3.0 x IULN (for subjects with documented bone metastasis, ALP ≤ 5.0 x IULN)
• Serum albumin ≥ 2.8 g/dL
• Serum creatine ≤ 1.5 x IULN or calculated creatinine clearance ≥ 40 mL/min by Cockcroft-Gault
• UPCR ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine

You may not qualify if:

• Pure well-differentiated liposarcoma or low grade leiomyosarcoma.
• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
• Prior treatment with zanzalintinib.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic, or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis within 2 weeks before first dose of study treatment; 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.
• Currently receiving any other investigational agents.
• Patients with untreated brain metastases. Patients with treated brain metastases are allowed if post-treatment brain-imaging after CNS-directed therapy shows no evidence of progression and disease is 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.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to zanzalintinib or eribulin or other agents used in the study.
• Concomitant anticoagulation with warfarin or other vitamin-K antagonists, direct thrombin inhibitors, or antiplatelet agents (e.g. 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Exelixis: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Related Links

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

MeSH Terms

Conditions

Sarcoma

Interventions

eribulin

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Mia C Weiss, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mia C Weiss, M.D.

CONTACT

314-747-3096; m.c.weiss@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: April 25, 2025
• First Posted: May 4, 2025
• Study Start: October 22, 2025
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): October 31, 2033
• Last Updated: October 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)