Non-small Cell Lung CancerPhase 1NCT05354102
A First-in-human (FIH) Combination Treatment Study With a Single Dose Level of BMC128
A Phase 1 study testing BMC128 and Nivolumab in people with Non-small Cell Lung Cancer and Melanoma, run by Biomica Ltd. at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer, Melanoma, Renal Cell Carcinoma
- What is being tested?
- BMC128 and Nivolumab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteIsrael
- Study dates
- 1 May 2022to Nov 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
- Female subjects of childbearing potential should have a negative urine pregnancy test within 72 hours prior to enrolment (enrolment = start of depletion phase). If urine pregnancy results cannot be confirmed as negative, a SERUM β-HCG pregnancy test is required. Subjects of childbearing potential are those who have not been surgically sterilized or those age < 60 y who have not been free from menses for ≥2 years.
- Female subjects of childbearing potential must be willing to use 2 methods of birth control starting from the start of the induction phase or be surgically sterile, or abstain from heterosexual activity throughout the course of the study and 120 days after the last dose of study medication
- Male subjects with female partners of childbearing potential should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
Who cannot join
- 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)
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- 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
- Receipt of a live-virus vaccination within 28 days of enrolment. COVID-19 vaccine is not mandatory. However, patients who have been vaccinated against COVID-19 prior to study entry, should have completed the primary series of vaccination (initial two doses of the vaccine) at least 3 days before enrolment.
- Known HIV infection, or active infection with hepatitis B or C
- History of (non-infectious) pneumonitis that required steroids or has current active pneumonitis
- Known additional malignancy either progressing or requiring active treatment (except for non-melanoma skin cancer, in situ cervical cancer or prostate intraepithelial neoplasia) within the last 2 years.
- Female subjects who are breastfeeding
- Known intolerance or hypersensitivity to study drugs
- Known intolerance or hypersensitivity to oral vancomycin or neomycin
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Known inability to orally ingest capsules
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label Study to Evaluate the Safety and Tolerability of BMC128 in Combination With Nivolumab in Patients With Non-small Cell Lung Cancer (NSCLC), Melanoma or Renal Cell Carcinoma (RCC)
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.
Read the detailed description
This phase 1, first-in-human, proof-of-concept, open-label, combination treatment study is designed to profile the safety and tolerability of BMC128 in combination with Nivolumab, its effect on the intestinal microbiome and the anti-tumor immune and inflammatory responses and its preliminary anti-tumor activity. A 14-day induction phase, in which patients will be treated with a single dose level of BMC128, will be initiated, followed by four 28-day treatment cycles of BMC128 in combination with Nivolumab. Thereafter, patients will be treated with Nivolumab as a monotherapy for up to 22 additional cycles, until disease progression (PD) or intolerable toxicity
- Conditions
- Non-small Cell Lung Cancer, Melanoma, Renal Cell Carcinoma
- Being tested
- BMC128, Nivolumab
- Keywords
- Microbiome
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Melanoma, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BMC128Drug
Also called LBP (Live Bacteria Product)
A live bio-therapeutic product composed of 4 commensal bacterial strains, natural inhabitants of the human intestinal tract.
NivolumabDrug
Also called Opdivo
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: BMC128; Drug: Nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2022
- Study start1 May 2022
- Primary completionMay 2024 (estimated)
- Study completionNov 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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)
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biomica Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ruth Perets, Dr., Principal investigator, Rambam MC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05354102
- Sponsor's protocol ID
- BMC128-001
- Status last verified
- May 2024
- First submitted
- 20 Apr 2022
- Last updated
- 7 May 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label Study to Evaluate the Safety and Tolerability of BMC128 in Combination With Nivolumab in Patients With Non-small Cell Lung Cancer (NSCLC), Melanoma or Renal Cell Carcinoma (RCC)
- ClinicalTrials.gov ID
- NCT05354102
- Acronym / sponsor ID
- BMC128-001
- Conditions
- Non-small Cell Lung Cancer, Melanoma, Renal Cell Carcinoma
- Keywords
- Microbiome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Biomica Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 May 2022 (actual)
- Primary completion
- May 2024 (estimated)
- Study completion
- Nov 2025 (estimated)
- First posted
- 29 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This phase 1, first-in-human, proof-of-concept, open-label, combination treatment study is designed to profile the safety and tolerability of BMC128 in combination with Nivolumab, its effect on the intestinal microbiome and the anti-tumor immune and inflammatory responses and its preliminary anti-tumor activity. A 14-day induction phase, in which patients will be treated with a single dose level of BMC128, will be initiated, followed by four 28-day treatment cycles of BMC128 in combination with Nivolumab. Thereafter, patients will be treated with Nivolumab as a monotherapy for up to 22 additional cycles, until disease progression (PD) or intolerable toxicity
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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)
| Arm | Type | Receives |
|---|---|---|
| BMC128 in combination with Nivolumab | Experimental | Drug: BMC128, Drug: NivolumabFour 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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:
Key exclusion criteria (24 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BMC128Also: LBP (Live Bacteria Product)A live bio-therapeutic product composed of 4 commensal bacterial strains, natural inhabitants of the human intestinal tract. | Drug | BMC128 in combination with Nivolumab |
| NivolumabAlso: OpdivoA 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. | Drug | BMC128 in combination with Nivolumab |
Primary outcome
Number and severity of drug-related treatment emergent adverse events (TEAEs)
Time frame: Through study completion, an average of 1 year
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).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ruth Perets, Dr. principal investigator
Rambam MC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BMC128 and Nivolumab in people with Non-small Cell Lung Cancer and Melanoma, run by Biomica Ltd. at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and severity of drug-related treatment emergent adverse events (TEAEs) (time frame: Through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 May 2024.