Adding Biotherapy or Placebo to Standard Treatment for Advanced Kidney Cancer

NCT07383441 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: S2419NCI-2026-00080U10CA180888
• Study Type: interventional
• Target: 718
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase III trial compares the effect of adding live biotherapy, MO-03, to standard of care (SOC) immunotherapy, including ipilimumab, nivolumab, axitinib, pembrolizumab, cabozantinib, and lenvatinib, to SOC immunotherapy alone in treating patients with clear cell renal cell cancer that may have spread from where it first started (primary site) to nearby tissue, lymph nodes, or distant parts of the body (advanced) or that has spread from where it first started to other places in the body (metastatic). Studies have shown that gut health (the gut microbiome) may impact the effectiveness of immunotherapy. The microbiome includes all of the bacteria and organisms naturally found in the digestive tract. MO-03, a type of biotherapy, contains material from living organisms that may help keep the digestive tract healthy and may help to increase the effect of immunotherapy. Immunotherapy with monoclonal antibodies, such as ipilimumab, nivolumab, pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Axitinib, cabozantinib, and lenvatinib are a type of angiogenesis inhibitor and tyrosine kinase inhibitor (TKI) that block certain proteins which may help keep tumor cells from growing and may also help prevent the growth of new blood vessels that tumors need to grow. Adding MO-03 to SOC immunotherapy may be more effective than SOC immunotherapy alone in treating patients with advanced or metastatic clear cell renal cell cancer.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Progression-free survival (PFS)

  A Cox model will be used to test the treatment hazard ratio with stratification factors in the model as covariates for the futility and efficacy interim analyses and the final analysis.

  From date of randomization to date of first documentation of progression, or death due to any cause, assessed up to 5 years

Secondary Outcomes (4)

• Incidence of adverse events (AEs) (Safety run-in)

  During the first 12 weeks (2 cycles [cycle length =42 days])

• Overall survival

  From date of randomization to date of death due to any cause, assessed up to 5 years

• PFS rates between the study arms

  At 12 and 24 months

• Incidence of AEs between study arms

  Up to 90 days after last dose of study treatment

Study Arms (2)

Arm 1 (MO-03, SOC immunotherapy)

EXPERIMENTAL

See Detailed Description

Drug: Axitinib; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib; Drug: Clostridium butyricum CBM 588 Probiotic Strain; Procedure: Computed Tomography; Biological: Ipilimumab; Drug: Lenvatinib; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Nivolumab and Recombinant Human Hyaluronidase; Biological: Pembrolizumab

Arm 2 (placebo, SOC immunotherapy)

PLACEBO COMPARATOR

See Detailed Description

Drug: Axitinib; Procedure: Biospecimen Collection; Procedure: Bone Scan; Drug: Cabozantinib; Procedure: Computed Tomography; Biological: Ipilimumab; Drug: Lenvatinib; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab; Drug: Nivolumab and Recombinant Human Hyaluronidase; Biological: Pembrolizumab; Drug: Placebo Administration

Interventions

Axitinib DRUG

Given PO

Also known as: AG 013736, AG-013736, AG013736, Inlyta

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Cabozantinib DRUG

Given PO

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Clostridium butyricum CBM 588 Probiotic Strain DRUG

Given PO

Also known as: C. butyricum CBM 588 Probiotic Strain, C. butyricum MIYAIRI Strain, C. butyricum Strain MIYAIRI 588, CBM 588, CBM588, Clostridium butyricum MIYAIRI 588, Clostridium butyricum MIYAIRI 588 Probiotic Strain, CLOSTRIDIUM BUTYRICUM MIYAIRI 588 STRAIN, MIYAIRI 588, MIYAIRI 588 Strain of C. butyricum

Arm 1 (MO-03, SOC immunotherapy)

Computed Tomography PROCEDURE

Undergo CT

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

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS 734016, BMS-734016, BMS734016, Ipilimumab Biosimilar CS1002, MDX 010, MDX-010, MDX-CTLA4, MDX010, Yervoy

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Lenvatinib DRUG

Given PO

Also known as: E 7080, E-7080, E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Nivolumab BIOLOGICAL

Given IV

Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Nivolumab and Recombinant Human Hyaluronidase DRUG

Given SC

Also known as: Hyaluronidase-nvhy and Nivolumab, Hyaluronidase/Nivolumab, Nivolumab and Hyaluronidase-nvhy, Nivolumab and rHuPH20, Nivolumab/Recombinant Human Hyaluronidase, Nivolumab/rHuPH20, Opdivo Qvantig

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Arm 1 (MO-03, SOC immunotherapy); Arm 2 (placebo, SOC immunotherapy)

Placebo Administration DRUG

Given PO

Arm 2 (placebo, SOC immunotherapy)

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed renal cell carcinoma (RCC) with clear cell component that is advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC at the time of registration on study
• Participants must have measurable/evaluable disease by RECIST 1.1 criteria. Participants with only bone metastases or only pleural effusions are considered evaluable disease and are eligible
• Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease must not require immediate central nervous system (CNS) specific treatment at the time of study registration or anticipated treatment during the first cycle of therapy
• Participants must not be currently enrolled or plan to participate in treatment studies while enrolled on this study
• Participants must not plan to take any over the counter probiotic supplements at time of study registration and while on protocol treatment
• NOTE: Vitamin and electrolyte or mineral supplements are permitted
• Participants must not have had prior systemic therapy for advanced or metastatic RCC or any treatment with immune based combination therapy
• NOTE: Participants can have prior neo/adjuvant treatment with an anti-PD-1, anti-PD-L1, and/or anti-CTLA-4 antibody or other therapies for any current or prior malignancy if \> 12 months prior to registration
• Participants must not be receiving steroid replacement therapy for adrenal insufficiency greater than 50 mg daily of hydrocortisone or prednisone equivalent dose at the time of registration
• Participants must not require the use of systemic corticosteroids \> 10 mg/day of prednisone or its equivalent for any reason other than replacement therapy for adrenal insufficiency
• Participants must not have received any systemic antibiotics within 7 days prior to registration
• NOTE: Uncontrolled infections must be completely resolved
• Participants must be ≥ 18 years old at the time of registration
• Participants must have a Zubrod performance status 0-2 within 28 days of registration
• Participants must be able to safely receive at least one of the standard of care regimens, per the current Food and Drug Administration (FDA)-approved package inserts, treating investigator's discretion, and institutional guidelines

Sponsors & Collaborators

• SWOG Cancer Research Network: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

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

Interventions

Axitinib; Specimen Handling; cabozantinib; Ipilimumab; CTLA-4 Antigen; lenvatinib; Magnetic Resonance Spectroscopy; Nivolumab; Hyaluronoglucosaminidase; pembrolizumab

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)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Spectrum Analysis; Chemistry Techniques, Analytical; Glycoside Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Polysaccharide-Lyases; Carbon-Oxygen Lyases; Lyases

Study Officials

• Pedro Barata

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Double blinded trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 3, 2026
• Study Start (Estimated): June 10, 2026
• Primary Completion (Estimated): January 31, 2033
• Study Completion (Estimated): January 31, 2034
• Last Updated: February 3, 2026

Record last verified: 2026-01