NCT05122546

Brief Summary

This phase I trial evaluates the effects of CBM588 in combination with standard therapies, nivolumab and cabozantinib, in treating patients with kidney cancer that has spread to other places in the body (advanced/metastatic). The digestive microbiome may have an effect on how patients respond to treatment, and previous research shows that a specific bacteria found in the gut (Bifidobacterium) may predispose participants to a better response to standard therapies. CBM588 is a strain of bacteria that can restore species of Bifidobacterium to the microbiome. The primary aim of this study is to determine how CBM588 changes the microbiome of patients with metastatic renal cell carcinoma. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving CBM588, nivolumab, and cabozantinib may kill more tumor cells.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
31

participants targeted

Target at P25-P50 for phase_1

Timeline
8mo left

Started Nov 2021

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress87%
Nov 2021Jan 2027

First Submitted

Initial submission to the registry

October 27, 2021

Completed
5 days until next milestone

Study Start

First participant enrolled

November 1, 2021

Completed
15 days until next milestone

First Posted

Study publicly available on registry

November 16, 2021

Completed
5.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 12, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 12, 2027

Last Updated

March 5, 2026

Status Verified

March 1, 2026

Enrollment Period

5.2 years

First QC Date

October 27, 2021

Last Update Submit

March 3, 2026

Conditions

Advanced Clear Cell Renal Cell CarcinomaAdvanced Papillary Renal Cell CarcinomaAdvanced Renal Cell CarcinomaAdvanced Sarcomatoid Renal Cell CarcinomaMetastatic Clear Cell Renal Cell CarcinomaMetastatic Papillary Renal Cell CarcinomaMetastatic Renal Cell CarcinomaMetastatic Sarcomatoid Renal Cell CarcinomaStage III Renal Cell Cancer AJCC v8Stage IV Renal Cell Cancer AJCC v8Unresectable Clear Cell Renal Cell CarcinomaUnresectable Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

  • Change in Bifidobacterium composition of stool

    Will be assessed for patients' stool sample

    Baseline to week 12 of therapy

Secondary Outcomes (7)

  • Comparison of the Shannon index (a measure of microbial diversity)

    Baseline to week 12 of therapy

  • Best overall response

    Up to 2 years

  • Progression-free survival

    From enrollment to progression, assessed up to 2 years

  • Proportion of circulating regulatory T-cells

    Baseline up to 2 years

  • Change in proportion of circulating myeloid-derived suppressor cells (MDSC)

    Baseline up to 2 years

  • +2 more secondary outcomes

Study Arms (2)

Arm 2 (CBM588, nivolumab, cabozantinib S-malate)

EXPERIMENTAL

Patients receive CBM588 PO BID, nivolumab IV over 30 minutes on day 1, and cabozantinib S-malate PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malateDrug: Clostridium butyricum CBM 588 Probiotic StrainBiological: Nivolumab

Arm I (nivolumab, cabozantinib S-malate)

ACTIVE COMPARATOR

Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib S-malate PO QD. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabozantinib S-malateBiological: Nivolumab

Interventions

Cabozantinib S-malateDRUG

Given PO

Also known as: BMS-907351, Cabometyx, Cometriq, XL-184, XL184
Arm 2 (CBM588, nivolumab, cabozantinib S-malate)Arm I (nivolumab, cabozantinib S-malate)
Clostridium butyricum CBM 588 Probiotic StrainDRUG

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, MIYAIRI 588, MIYAIRI 588 Strain of C. butyricum
Arm 2 (CBM588, nivolumab, cabozantinib S-malate)
NivolumabBIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo
Arm 2 (CBM588, nivolumab, cabozantinib S-malate)Arm I (nivolumab, cabozantinib S-malate)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histological confirmation of renal cell carcinoma (RCC) with a clear-cell, papillary or sarcomatoid component
  • Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) RCC
  • No prior systemic therapy for RCC with the following exception:
  • One prior adjuvant or neoadjuvant therapy for completely resectable RCC if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
  • Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Recovery to baseline or =\< grade 1 CTCAE v5 from toxicities related to any prior treatments unless adverse events (AE\[s\]) are clinically nonsignificant and/or stable on supportive therapy
  • Karnofsky performance status \>= 70%
  • Males and females, ages \>= 18
  • Any ethnicity or race
  • Absolute neutrophil count (ANC) \>= 1500/uL without granulocyte colony-stimulating factor support (within 14 days before first dose of study treatment)
  • White blood cell count \>= 2500/uL (within 14 days before first dose of study treatment)
  • Platelets \>= 100,000/uL without transfusion (within 14 days before first dose of study treatment)
  • Hemoglobin \>= 9 g/dL (\>= 90 g/L) (within 14 days before first dose of study treatment)
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) =\< 3 x upper limit of normal (ULN). ALP =\< 5 x ULN with documented bone metastases (within 14 days before first dose of study treatment)
  • Total bilirubin =\< 1.5 x ULN (for subjects with Gilbert's disease =\< 3 x ULN) (within 14 days before first dose of study treatment)
  • +7 more criteria

You may not qualify if:

  • Prior treatment with cabozantinib
  • Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment
  • Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
  • Known medical condition (e.g., a condition associated with 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
  • 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 or 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 prior to first dose of study treatment after radiotherapy or at least 4 weeks prior to first dose of study treatment after major surgery (e.g., removal or biopsy of brain metastasis). Subjects must have complete wound healing from major surgery or minor surgery before first dose of study treatment. Eligible subjects must be neurologically asymptomatic and without corticosteroid treatment at the time of first dose of study treatment
  • Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g., dabigatran), direct factor Xa inhibitor betrixaban, or 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 or the tumor
  • Administration of a live, attenuated vaccine within 30 days before first dose of study treatment
  • The subject has uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions:
  • Cardiovascular disorders:
  • Congestive heart failure New York Heart Association class 3 or 4, unstable angina pectoris, serious cardiac arrhythmias
  • +32 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

  • Ebrahimi H, Dizman N, Meza L, Malhotra J, Li X, Dorff T, Frankel P, Llamas-Quitiquit M, Hsu J, Zengin ZB, Alcantara M, Castro D, Mercier B, Chawla N, Chehrazi-Raffle A, Barragan-Carrillo R, Jaime-Casas S, Govindarajan A, Gillece J, Trent J, Lee PP, Parks TP, Takahashi M, Hayashi A, Kortylewski M, Caporaso JG, Lee K, Tripathi A, Pal SK. Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. 2024 Sep;30(9):2576-2585. doi: 10.1038/s41591-024-03086-4. Epub 2024 Jun 28.

    PMID: 38942995DERIVED

MeSH Terms

Conditions

Clear-cell metastatic renal cell carcinomaCarcinoma, Renal Cell

Interventions

cabozantinibNivolumab

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsKidney NeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesKidney DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Sumanta K Pal

    City of Hope Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 27, 2021

First Posted

November 16, 2021

Study Start

November 1, 2021

Primary Completion (Estimated)

January 12, 2027

Study Completion (Estimated)

January 12, 2027

Last Updated

March 5, 2026

Record last verified: 2026-03

Locations

US(1)