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

NCT ID: NCT06399419

Last Updated: 2024-05-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-19
• Study Completion Date: 2026-10-19

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.

Detailed Description

PRIMARY OBJECTIVE:

I. To evaluate the safety and tolerability of nivolumab/ipilimumab with escalating doses of Clostridium butyricum MIYAIRI 588 capsules (CBM588) in patients with metastatic renal cell carcinoma.

SECONDARY OBJECTIVES:

I. To evaluate the effect of CBM588 on the clinical efficacy of nivolumab/ipilimumab.

II. To determine the effect of CBM588 (in combination with nivolumab/ipilimumab) in modulation of the gut microbiome in patients with metastatic renal cell carcinoma.

III. To assess the effect of CBM588 on the change of metabolic pathways with the nivolumab/ipilimumab combination in patients with metastatic renal cell carcinoma.

IV. To determine the effect of CBM588 on systemic immunomodulation.

OUTLINE: This is a dose-escalation study of CBM588 followed by a dose-expansion study.

Patients receive CBM588 capsules orally (PO) twice daily (BID) on days 1-21, nivolumab intravenously (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 computed tomography (CT), bone scan and blood sample collection throughout the study. Patients may optionally undergo magnetic resonance imaging (MRI) on study.

After completion of study treatment, patients are followed up once a year.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (CBM588 capsules, nivolumab, ipilimumab)

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.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo blood sample collection

Bone Scan

Intervention Type: PROCEDURE

Undergo bone scan

CBM588 Capsules

Intervention Type: BIOLOGICAL

Given PO

Computed Tomography

Intervention Type: PROCEDURE

Undergo CT

Ipilimumab

Intervention Type: BIOLOGICAL

Given IV

Magnetic Resonance Imaging

Intervention Type: PROCEDURE

Undergo MRI

Nivolumab

Intervention Type: BIOLOGICAL

Given IV

Interventions

Biospecimen Collection

Undergo blood sample collection

Intervention Type: PROCEDURE

Bone Scan

Undergo bone scan

Intervention Type: PROCEDURE

CBM588 Capsules

Given PO

Intervention Type: BIOLOGICAL

Computed Tomography

Undergo CT

Intervention Type: PROCEDURE

Ipilimumab

Given IV

Intervention Type: BIOLOGICAL

Magnetic Resonance Imaging

Undergo MRI

Intervention Type: PROCEDURE

Nivolumab

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; Bone Scintigraphy; CBM588; Clostridium butyricum MIYAIRI 588; C. butyricum MIYAIRI 588; C. butyricum strain MIYAIRI 588; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized axial tomography (procedure); Computerized Tomography; Computerized Tomography (CT) scan; CT; CT Scan; tomography; Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody; BMS-734016; Ipilimumab Biosimilar CS1002; MDX-010; MDX-CTLA4; Yervoy; 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; ABP 206; BCD-263; BMS-936558; CMAB819; MDX-1106; NIVO; Nivolumab Biosimilar ABP 206; Nivolumab Biosimilar BCD-263; Nivolumab Biosimilar CMAB819; ONO-4538; Opdivo

Eligibility Criteria

Inclusion Criteria

• 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
• Hemoglobin ≥ 8 g/dL
• 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
• Total bilirubin ≤ 1.5 x ULN (for subjects with Gilbert's disease ≤ 3 x ULN)
• Serum albumin ≥ 2.8 g/dl
• Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test < 1.3 x the laboratory ULN
• Serum calculated creatinine clearance ≥ 50mL/min using the Cockcroft-Gault equation
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (e.g., barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 5 months after the last dose of nivolumab for women with childbearing potential, and 7 months after the last dose of nivolumab for men
• Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes. In addition, females < 55 years-of-age must have a serum follicle stimulating (FSH) level > 40 mIU/mL to confirm menopause).

• Note: Documentation may include review of medical records, medical examinations, or medical history interview by study site

Exclusion Criteria

• 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
• Moderate to severe hepatic impairment (Child-Pugh B or C)
• Requirement for hemodialysis or peritoneal dialysis
• History of solid organ or allogenic stem cell transplant
• Other clinically significant disorders that would preclude safe study participation

• Any active, known, or suspected autoimmune disease will be excluded, with the following exceptions:

• Type 1 diabetes mellitus
• Hypothyroidism only requiring hormone replacement
• Skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment
• Conditions not expected to recur in the absence of an external trigger
• Pregnant or lactating females
• Inability to swallow tablets/capsules or unwillingness or inability to receive IV administration
• Previously identified allergy or hypersensitivity to components of the study treatment formulations or history of severe infusion-related reactions to monoclonal antibodies. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption are also excluded
• Any other active malignancy at time of first dose of study treatment or diagnosis of another malignancy within 3 years prior to first dose of study treatment that requires active treatment, except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast
• Exclusion of subjects with a 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
• Exclusion of subjects whose baseline pulse oximetry is less than 92% on room air
• Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

City of Hope Medical Center

OTHER

Sponsor Role: collaborator

Miyarisan Pharmaceuticals, Co., Ltd.

UNKNOWN

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Osel, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alex Chehrazi-Raffle, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Site Status: RECRUITING

Countries

United States

Facility Contacts

Alex Chehrazi-Raffle, MD

Role: primary

achehraziraffle@coh.org

626-218-4772

References

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.

Reference Type: BACKGROUND

PMID: 35228755 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 32665261 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 35655708 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38201474 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 38385162 (View on PubMed)

Other Identifiers

NCI-2024-03079

Identifier Type: REGISTRY

Identifier Source: secondary_id

23554

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23554

Identifier Type: -

Identifier Source: org_study_id

NCT06414642

Identifier Type: -

Identifier Source: nct_alias