CBM588, Nivolumab, and Ipilimumab in Treating Patients With Stage IV or Advanced Kidney Cancer

NCT03829111 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: 18523NCI-2019-00248P30CA033572
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies how well CBM588 works when given together with nivolumab and ipilimumab in treating patients with kidney cancer that is stage IV or has spread to other places in the body (advanced). CBM588 is a probiotic that may help to increase the effect of immunotherapy. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving CBM588, nivolumab, and ipilimumab may work better in treating patients with kidney cancer.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Change in Bifidobacterium composition of stool

  Will be assessed for patients on both arms.

  Baseline up to week 12

Secondary Outcomes (3)

• Change in Shannon index

  Baseline up to week 12

• Best overall response

  Up to 2 years

• Progression-free survival (PFS)

  From enrollment to progression, assessed up to 2 years

Other Outcomes (4)

• Change in proportion of circulating regulatory T-cells (Tregs)

  Baseline up to 2 years

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

  Baseline up to 2 years

• Change in IL-6, IL-8, and other cytokines/chemokines levels

  Baseline up to 2 years

Study Arms (2)

Arm I (nivolumab, ipilimumab)

ACTIVE COMPARATOR

Patients receive nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, patients receive nivolumab IV over 30 minutes on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Biological: Nivolumab

Arm II (CBM588, nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive clostridium butyricum CBM 588 probiotic strain PO BID, nivolumab IV over 30 minutes on day 1, and ipilimumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Beginning in cycle 5, treatment with clostridium butyricum CBM 588 probiotic strain and nivolumab repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Clostridium butyricum CBM 588 Probiotic Strain; Biological: Ipilimumab; Biological: Nivolumab

Interventions

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, MIYAIRI 588, MIYAIRI 588 Strain of C. butyricum

Arm II (CBM588, nivolumab, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

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

Arm I (nivolumab, ipilimumab); Arm II (CBM588, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, MDX-1106, NIVO, ONO-4538, Opdivo

Arm I (nivolumab, ipilimumab); Arm II (CBM588, nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide informed consent for the trial
• Histological confirmation of RCC with a clear-cell component
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) RCC
• Intermediate or poor risk disease by International Metastatic RCC Database Consortium (IMDC) classification
• No prior systemic therapy for RCC with the following exception:
• One prior adjuvant or neoadjuvant therapy for completely resectable RCC if such therapy did not include an agent that targets PD-1 or PD-L1 and if recurrence occurred at least 6 months after the last dose of adjuvant or neoadjuvant therapy
• Eastern Cooperative Oncology Group (ECOG) performance status \< 2
• Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Any ethnicity or race
• Calculated creatinine clearance \>= 30 milliliters per minute (mL/min) per the Cockcroft and Gault formula or serum creatinine \< 1.5 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \< 3 x ULN (\< 5 x ULN if liver metastases are present)
• Total bilirubin \< 1.5 x ULN (except subjects with Gilbert syndrome, who can have total bilirubin up to 3.0 mg/dL)
• White blood cells (WBC) \> 2,000/mm\^3
• Neutrophils \> 1,500/mm\^3
• Platelets \> 100,000/mm\^3

You may not qualify if:

• Presence of untreated brain metastases. Patients with treated brain metastases must be stable for 4 weeks after completion of treatment and have documented stability on pre-study imaging. Patients must have no clinical symptoms from brain metastases and have no requirement for systemic corticosteroids amounting to \> 10 mg/day of prednisone or its equivalent for at least 2 weeks prior to first dose of study drug. Patients with known leptomeningeal metastases are excluded, even if treated
• Not recovered to =\< grade 1 toxicities related to any prior therapy before administration of study drug
• Favorable risk disease by IMDC classification
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Any active or recent history of a known or suspected autoimmune disease or recent history of a syndrome that required systemic corticosteroids (\> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Subjects with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll
• Active interstitial lung disease (ILD)/pneumonitis or history of ILD/pneumonitis requiring treatment with systemic steroids
• Baseline pulse oximetry less than 92% "on room air"
• Current use, or intent to use, probiotics, yogurt or bacterial fortified foods during the period of treatment
• Any condition requiring systemic treatment with corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses \> 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
• Uncontrolled adrenal insufficiency
• 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
• Not recovered to =\< grade 1 toxicities related to any prior therapy before administration of study drug
• Women who are pregnant or breastfeeding
• History of myocarditis or congestive heart failure (as defined by New York Heart Association functional classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry
• White blood cells (WBC) \< 2,000/mm\^3

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

Related Publications (2)

• Villemin C, Six A, Neville BA, Lawley TD, Robinson MJ, Bakdash G. The heightened importance of the microbiome in cancer immunotherapy. Trends Immunol. 2023 Jan;44(1):44-59. doi: 10.1016/j.it.2022.11.002. Epub 2022 Dec 1.

  PMID: 36464584 DERIVED

• Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, Lyou Y, Frankel P, Cui Y, Mira V, Llamas M, Hsu J, Zengin Z, Salgia N, Salgia S, Malhotra J, Chawla N, Chehrazi-Raffle A, Muddasani R, Gillece J, Reining L, Trent J, Takahashi M, Oka K, Higashi S, Kortylewski M, Highlander SK, Pal SK. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. Nat Med. 2022 Apr;28(4):704-712. doi: 10.1038/s41591-022-01694-6. Epub 2022 Feb 28.

  PMID: 35228755 DERIVED

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Ipilimumab; CTLA-4 Antigen; Nivolumab

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)

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

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: February 1, 2019
• First Posted: February 4, 2019
• Study Start: May 14, 2019
• Primary Completion: December 13, 2023
• Study Completion: December 13, 2023
• Last Updated: July 3, 2024

Record last verified: 2024-07

Locations

US (1)