CBM588 Capsules in Combination With Nivolumab and Ipilimumab for the Treatment of Advanced Stage Kidney Cancer

NCT06399419 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 23554NCI-2024-03079P30CA033572
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, best dose, and effectiveness of CBM588 in combination with nivolumab and ipilimumab in treating patients with kidney cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). CBM588 is a live biotherapeutic that may help improve the effects of immunotherapy. Nivolumab and ipilimumab are monoclonal antibodies that may interfere with the ability of tumor cells to grow and spread by enhancing the ability of the body's immune cells to attack tumor cells. CBM588 in combination with nivolumab and ipilimumab may be safe, tolerable, and/or effective in treating patients with advanced stage kidney cancer.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• Dose limiting toxicity (DLT)

  Toxicities at least possibly related to study agent will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.

  Up to 28 days

• Maximum tolerated dose (MTD)

  MTD estimate will be the highest dose with the occurrence of DLT in no more than 1 out of 6 of the patients.

  Up to 28 days

• Incidence of adverse events (AEs)

  AEs will be graded using CTCAE. Summaries will be provided overall and by dose group. The number and percentage of subjects reporting treatment-emergent AEs (TEAE) will be summarized overall and by the worse CTCAE grade, with a breakdown by dose. The number and percentage of subjects reporting TEAEs considered related to each study drug will be summarized.

  Up to 3 years

Secondary Outcomes (8)

• Progression free survival (PFS)

  From enrollment to progression or death, assessed up to 3 years

• Overall response rate (ORR)

  Up to 3 years

• Change in stool microbial diversity

  Baseline to week 12 of therapy

• Change in abundancies of gut microbiome species

  Baseline to week 12 of therapy

• Metabolic pathways

  Baseline to week 12 of therapy

Study Arms (1)

Treatment (CBM588 capsules, nivolumab, ipilimumab)

EXPERIMENTAL

Patients receive CBM588 PO BID on days 1-21, nivolumab IV over 30 minutes and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles. Patients then receive CBM588 PO BID on days 1-28 and nivolumab IV on day 1. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT, bone scan and blood sample collection throughout the study. Patients may optionally undergo MRI on study.

Procedure: Biospecimen Collection; Procedure: Bone Scan; Biological: CBM588 Capsules; Procedure: Computed Tomography; Biological: Ipilimumab; Procedure: Magnetic Resonance Imaging; Biological: Nivolumab

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Treatment (CBM588 capsules, nivolumab, ipilimumab)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Treatment (CBM588 capsules, nivolumab, ipilimumab)

CBM588 Capsules BIOLOGICAL

Given PO

Also known as: CBM588, Clostridium butyricum MIYAIRI 588, C. butyricum MIYAIRI 588, C. butyricum strain MIYAIRI 588

Treatment (CBM588 capsules, nivolumab, ipilimumab)

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, tomography

Treatment (CBM588 capsules, nivolumab, ipilimumab)

Ipilimumab BIOLOGICAL

Given IV

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

Treatment (CBM588 capsules, nivolumab, ipilimumab)

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

Treatment (CBM588 capsules, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

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

Treatment (CBM588 capsules, nivolumab, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principle investigator (PI) approval
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Age ≥ 18 years
• Histologically confirmed renal cell carcinoma with clear cell renal cell carcinoma component or sarcomatoid component
• Advanced (not amenable to curative surgery or radiation therapy) or metastatic (American Joint Committee on Cancer \[AJCC\] stage IV) renal cell carcinoma with intermediate- or poor-risk disease by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria
• No prior systemic therapy for renal cell carcinoma (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 by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• Absolute neutrophil count (ANC) ≥ 1500/uL without granulocyte colony-stimulating factor support
• White blood cell count ≥ 2500/uL
• Platelets ≥ 100,000/uL without transfusion

You may not qualify if:

• Prior treatment with ipilimumab and/or nivolumab
• Current use, or intent to use, probiotics, yogurt, or bacterial fortified foods during the period of treatment
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• 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 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
• 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:
• Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days before first dose of study treatment. Note: Inhaled, intranasal, intra-articular, or topical steroids are permitted. Adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent are permitted. Transient short-term use of systemic corticosteroids for allergic conditions (e.g., contrast allergy) is also allowed
• Active infection requiring systemic treatment. Acute or chronic hepatitis B or C infection, known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness requiring systemic treatments, or known positive test for tuberculosis infection where there is clinical or radiographic evidence of active mycobacterial infection
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
• Malabsorption syndrome
• Uncompensated/symptomatic hypothyroidism

Sponsors & Collaborators

• Osel, Inc.: lead
• City of Hope Medical Center: collaborator
• Miyarisan Pharmaceuticals, Co., Ltd.: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

RECRUITING

Related Publications (5)

• 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 BACKGROUND

• Tomita Y, Ikeda T, Sakata S, Saruwatari K, Sato R, Iyama S, Jodai T, Akaike K, Ishizuka S, Saeki S, Sakagami T. Association of Probiotic Clostridium butyricum Therapy with Survival and Response to Immune Checkpoint Blockade in Patients with Lung Cancer. Cancer Immunol Res. 2020 Oct;8(10):1236-1242. doi: 10.1158/2326-6066.CIR-20-0051. Epub 2020 Jul 14.

  PMID: 32665261 BACKGROUND

• Tomita Y, Goto Y, Sakata S, Imamura K, Minemura A, Oka K, Hayashi A, Jodai T, Akaike K, Anai M, Hamada S, Iyama S, Saruwatari K, Saeki S, Takahashi M, Ikeda T, Sakagami T. Clostridium butyricum therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors. Oncoimmunology. 2022 May 27;11(1):2081010. doi: 10.1080/2162402X.2022.2081010. eCollection 2022.

  PMID: 35655708 BACKGROUND

• Tomita Y, Sakata S, Imamura K, Iyama S, Jodai T, Saruwatari K, Hamada S, Akaike K, Anai M, Fukusima K, Takaki A, Tsukamoto H, Goto Y, Motozono C, Sugata K, Satou Y, Ueno T, Ikeda T, Sakagami T. Association of Clostridium butyricum Therapy Using the Live Bacterial Product CBM588 with the Survival of Patients with Lung Cancer Receiving Chemoimmunotherapy Combinations. Cancers (Basel). 2023 Dec 21;16(1):47. doi: 10.3390/cancers16010047.

  PMID: 38201474 BACKGROUND

• Paz Del Socorro T, Oka K, Boulard O, Takahashi M, Poulin LF, Hayashi A, Chamaillard M. The biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorgammat+Treg and PD-1 blockade efficacy. Gut Microbes. 2024 Jan-Dec;16(1):2315631. doi: 10.1080/19490976.2024.2315631. Epub 2024 Feb 22.

  PMID: 38385162 BACKGROUND

MeSH Terms

Conditions

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

Interventions

Specimen Handling; Ipilimumab; CTLA-4 Antigen; Magnetic Resonance Spectroscopy; 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)

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

Study Officials

• Alex Chehrazi-Raffle, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2024
• First Posted: May 3, 2024
• Study Start: June 19, 2024
• Primary Completion (Estimated): October 19, 2026
• Study Completion (Estimated): October 19, 2026
• Last Updated: May 30, 2024

Record last verified: 2024-05

Locations

US (1)