Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma

NCT07283731 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2025-0952NCI-2025-09246
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

To learn if zanzalintinib and pembrolizumab can help to control select subtypes of advanced/metastatic soft-tissue sarcoma (UPS, MFS, HGPS, and HGUS

Conditions

Phase 2; Zanzalintinib; Pembrolizumab; Advanced/Metastatic; Soft-Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Single Arm

EXPERIMENTAL

Treatment with Zanzalintinib + Pembrolizumab

Drug: Zanzalintinib; Drug: Pembrolizumab

Interventions

Zanzalintinib DRUG

Given by po

Single Arm

Pembrolizumab DRUG

Given by iv

Single Arm

Eligibility Criteria

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

You may not qualify if:

• Prior treatment with immune checkpoint inhibitors (ICIs)
• 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.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the exception of alopecia.
• Participants with clinically relevant ongoing complications from prior radiation therapy are not eligible. Additionally, if participants have received radiation therapy within 4 weeks or systemic therapy with radionucleotides within 6 weeks they are not eligible.
• Participants who are receiving any other investigational agents, as well as cytotoxic or biological systemic anticancer therapy including investigational treatments within 4 weeks of initiating study treatment are excluded.
• 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 of deteriorating cardiovascular disorders • Congestive heart failure New York Heart Association Class 3 or 4, unstable angina pectoris, new-onset angina, serious cardiac arrhythmias (eg, ventricular flutter, ventricular fibrillation, Torsade's de pointes).
• Uncontrolled hypertension defined as sustained blood pressure (BP) \> 140 mm Hg systolic or \> 90 mm Hg diastolic despite optimal antihypertensive treatment.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Exelixis: collaborator

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Sarcoma

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type

Study Officials

• Michael S Nakazawa, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Michael S Nakazawa, MD

CONTACT

(713) 410-3409; msnakazawa@mdanderson.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

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: December 16, 2025
• Study Start (Estimated): June 2, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2030
• Last Updated: April 17, 2026

Record last verified: 2026-04

Locations

US (1)