A First-in-human (FIH) Combination Treatment Study With a Single Dose Level of BMC128

NCT05354102 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: BMC128-001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the safety and tolerability of BMC128 in combination with nivolumab (a known immunotherapy) in order to investigate if administration of select elements of the intestinal microbiome may serve as a novel and effective means of improving the efficacy of anti-cancer immunotherapies.

Conditions

Non-small Cell Lung Cancer; Melanoma; Renal Cell Carcinoma

Keywords

Microbiome

Outcome Measures

Primary Outcomes (1)

• Number and severity of drug-related treatment emergent adverse events (TEAEs)

  Safety and tolerability assessments will be based on frequency, severity, and duration of treatment-related AEs, including clinically significant changes from baseline in physical examination findings, vital signs, ECOG, and safety laboratory tests. All treatment-emergent adverse events (TEAEs) will be graded using NCI Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0 or higher).

  Through study completion, an average of 1 year

Other Outcomes (1)

• The clinical effects of combined BMC128 and nivolumab treatment

  Through study completion, an average of 1 year

Study Arms (1)

BMC128 in combination with Nivolumab

EXPERIMENTAL

Four 28-day treatment cycles of the standard Nivolumab treatment protocol (480 mg on Day 1 of each cycle) together with a QD regimen of BMC128, followed by a Iong-term Nivolumab monotherapy. Prior to starting this combination treatment, patients will undergo: I. Native microbiota depletion stage - patients will be treated with oral Vancomycin 500mg in combination with Neomycin 1000mg, q6h for 72 hours. II. BMC128 monotherapy induction stage - One BMC128 capsule will be administered once daily QD for a period of 14 days.

Drug: BMC128; Drug: Nivolumab

Interventions

BMC128 DRUG

A live bio-therapeutic product composed of 4 commensal bacterial strains, natural inhabitants of the human intestinal tract.

Also known as: LBP (Live Bacteria Product)

BMC128 in combination with Nivolumab

Nivolumab DRUG

A human monoclonal antibody that blocks programmed-death-1 (PD-1). It is a type of immunotherapy and works as a checkpoint inhibitor, blocking a signal that prevents activation of T cells from attacking the cancer.

Also known as: Opdivo

BMC128 in combination with Nivolumab

Eligibility Criteria

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

You may qualify if:

• Capable of providing signed informed consent to participate in the study, and to comply with the requirements and restrictions listed in the protocol.
• ≥18 years of age at time of informed consent
• Histologically or cytologically confirmed metastatic or locally advanced unresectable clear cell renal cell carcinoma (ccRCC), cutaneous melanoma, or EGFR/ ALK wildtype adenocarcinoma-type non-small cell lung carcinoma (NSCLC).
• At least one measurable lesion per RECIST v 1.1 criteria
• Subjects must have progressed on treatment with a PD-1/PD-L1 inhibitor administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1/PDL-1 inhibitor treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of a PD-1/PD-L1 inhibitor.
• Has demonstrated disease progression after PD-1/PD-L1 therapy as defined by RECIST v1.1, iRECIST or irRECIST. The initial evidence of disease progression (PD) is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression.
• Progressive disease has been documented within 12 weeks from the last dose of a PD-1/PD-L1 inhibitor.
• Subjects must have had prior response to anti-PD1/PDL-1 as single agent or in combination with other cancer therapies, defined as at least stable disease per iRECIST, as assessed by 2 consecutive imaging ≥ 4 weeks apart, with the first one performed no earlier than 9 weeks from initiation of anti PD1/PDL-1 treatment.
• Subjects must demonstrate adequate organ functions at Screening:
• Absolute neutrophil count ≥1500/μL, platelet count ≥100,000/μL; hemoglobin ≥9.0 g/dL Note: Patients must not have received any growth factors or blood transfusions within 28 days prior to the Screening hematologic laboratory tests
• Total bilirubin \<1.5 × the upper limit of normal (ULN) (with the exception of patients diagnosed with Gilbert syndrome), Alanine aminotransferase or aspartate aminotransferase \<1.5 × ULN
• Creatinine ≤ 1.5 ULN and/or estimated glomerular filtration rate ≥ 60
• Albumin \>30 g/L (3.0 g/dL)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1

You may not qualify if:

• History of partial or complete colon resection or colonic dissemination of tumor.
• Active brain metastases or leptomeningeal disease. Subjects with asymptomatic central nervous system (CNS) metastases which have been stable (defined as without evidence of progression by magnetic resonance imaging (MRI) for at least 42 days prior to enrolment (initiation of depletion phase) and any neurologic symptoms have returned to baseline) following treatment with surgery or radiation therapy are allowed.
• Prior solid organ or hematologic transplant.
• Prior treatment with PD1/ PDL-1 inhibitor in combination with an immune-modifying microbiome agent.
• History of treatment-related immune-mediated (or immune-related) adverse reactions to immune-modulatory agents (including but not limited to anti-PD1/PD-L1 agents, anti-CTLA4 monoclonal antibodies) that caused permanent discontinuation of the agent, or that were grade 3 or 4 in severity. Subjects with grade 3-4 hypothyroidism, primary adrenal insufficiency or diabetes mellitus which are asymptomatic following adequate supplementation, will be eligible.
• Treatment with chemotherapy, immunotherapy, biologic therapy (except for denosumab and bisphosphonates), or other investigational agents \<21 days of enrolment (initiation of depletion phase)
• Palliative radiotherapy within 14 days or less from enrolment.
• Comorbidity requiring corticosteroid therapy (\>10mg prednisone/day or equivalent) within 7 days of enrolment. Physiologic replacement doses are allowed if they are ≤10mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Inhaled, intranasal or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder.
• Significant cardiac disease; New York Heart Association classification for chronic heart failure III-IV, symptomatic coronary artery disease, significant ventricular arrhythmias, myocardial infarction within 6 months, unstable, poorly controlled angina pectoris
• Active, known or suspected autoimmune disease that has required systemic treatment within the past 2 years (i.e., with use of disease-modifying agents, corticosteroids or immunosuppressive drugs), except for replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.).
• Note: corticosteroids given within 24 hours of an imaging study for purposes of pre-medication in subjects with hypersensitivity to radiologic contrast agents are allowed
• Serious active infection requiring systemic therapy
• Subject has completed a course of antibiotics within the four weeks prior to enrollment
• Subjects, who, in the opinion of the investigator, have predisposing risk factors for recurrent infections requiring systemic antibiotic treatment (i.e., fistulae, obstructing pulmonary mass, non-healing wound)
• A known psychiatric or substance abuse disorder that would interfere with the subject's ability to cooperate with the requirements of the trial

Sponsors & Collaborators

• Biomica Ltd.: lead

Study Sites (1)

Rambam MC

Haifa, Israel

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Melanoma; Carcinoma, Renal Cell

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; 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

Study Officials

• Ruth Perets, Dr.

  Rambam MC

  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

Model Details: One dose level of BMC128 will be investigated in combination with Nivolumab using a 3+3 model (Part A), followed by an expansion cohort (part B)

Study Record Dates

• First Submitted: April 20, 2022
• First Posted: April 29, 2022
• Study Start: May 1, 2022
• Primary Completion: May 1, 2024
• Study Completion: November 1, 2025
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)