Zanzalintinib and MO-03 for the Treatment of Metastatic Renal Cell Cancer After Progression on Immunotherapy

NCT07578025 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: 24926NCI-2026-02916P30CA033572
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well zanzalintinib and MO-03 works for the treatment of renal cell cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and that is growing, spreading, or getting worse (progression) after receiving immunotherapy. Zanzalintinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. MO-03 is a type of medication called a microbiome-based immunomodulator. It helps control some of the bacteria found in the gut which may make the zanzalintinib more effective. Giving zanzalintinib with MO-03 may be effective for treating metastatic renal cell cancer after progression on immunotherapy.

Conditions

Stage IV Renal Cell Cancer AJCC v8; Metastatic Clear Cell Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate

  Will be calculated as the number of patients with complete or partial response (per Response Evaluation Criteria in Solid Tumors version 1.1) divided by the total number of treated/evaluable subjects.

  Up to 2 years

Secondary Outcomes (11)

• Change in gut microbiota composition in stool

  From baseline to week 12

• Microbial diversity

  From baseline to week 12

• Proportion of circulating regulatory T cells

  At baseline, week 9, 13, 17 and 25

• Proportion of circulating myeloid-derived suppressor cells

  At baseline, week 9, 13, 17 and 25

• Cytokine levels

  At baseline, week 9, 13, 17 and 25

Study Arms (1)

Treatment (zanzalintinib and MO-03)

EXPERIMENTAL

Patients receive XL092 PO QD and MO-03 PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Study treatment may continue after progression if the Investigator believes that the subject is still receiving clinical benefit. Patients undergo CT scan, bone scan, and blood and urine sample collection throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: C. butyricum CBM 588 Probiotic Strain Capsule Formulation MO-03; Procedure: Computed Tomography; Drug: Zanzalintinib

Interventions

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (zanzalintinib and MO-03)

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (zanzalintinib and MO-03)

C. butyricum CBM 588 Probiotic Strain Capsule Formulation MO-03 DRUG

Given PO

Also known as: CBM588 Capsule Formulation MO-03, CBM588 Capsule MO-03, Clostridium butyricum CBM 588 Probiotic Strain Capsule Formulation MO-03, Clostridium butyricum CBM 588 Probiotic Strain Capule MO-03, Clostridium butyricum MIYAIRI 588 Capsule Formulation MO-03, MO 03, MO-03, MO03

Treatment (zanzalintinib and MO-03)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (zanzalintinib and MO-03)

Zanzalintinib DRUG

Given PO

Also known as: Multi-kinase Inhibitor XL092, XL 092, XL-092, XL092

Treatment (zanzalintinib and MO-03)

Eligibility Criteria

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

You may qualify if:

• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Gender: Males and females are eligible
• Any ethnicity or race
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Histologically confirmed renal cell carcinoma with a clear-cell histology
• Patients must have received one or two prior lines of systemic therapy for metastatic disease, which must include prior treatment with a checkpoint inhibitor and cabozantinib (not necessarily in the same line). Prior use of hypoxia-inducible factor (HIF) inhibitors or other tyrosine kinase inhibitors (TKIs) other than cabozantinib are not allowed
• Measurable metastatic disease by RECIST v 1.1 criteria
• Recovery to baseline or ≤ grade 1 severity (CTCAE v 6.0) 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 (e.g., physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ grade 2 hypomagnesemia, ≤ grade 2 neuropathy are permitted)
• White blood cell (WBC) \> 2,000/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• NOTE: Growth factor is not permitted within 14 days of absolute neutrophil count (ANC) assessment unless cytopenia is secondary to disease involvement
• Neutrophils ≥ 1,500/mm\^3 (to be performed within 14 days prior to day 1 of protocol therapy unless otherwise stated)
• NOTE: Growth factor is not permitted within 14 days of absolute neutrophil count (ANC) assessment unless cytopenia is secondary to disease involvement

You may not qualify if:

• Prior treatment with zanzalintinib
• 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, 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
• Known medical condition (e.g., chronic diarrhea or acute diverticulitis) that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results
• Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin inhibitors ) and platelet inhibitors (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
• Any complementary medications (e.g., 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 (e.g., ventricular flutter, ventricular fibrillation, Torsades de pointes).

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinoma; Carcinoma, Renal Cell

Interventions

Specimen Handling

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Sumanta K Pal

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

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: May 5, 2026
• First Posted: May 11, 2026
• Study Start (Estimated): November 28, 2026
• Primary Completion (Estimated): June 24, 2028
• Study Completion (Estimated): June 24, 2028
• Last Updated: May 11, 2026

Record last verified: 2026-05

Locations

US (1)