Melanoma Stage IVPhase 1/2NCT04521075
A Phase Ib Trial to Evaluate the Safety and Efficacy of FMT and Nivolumab in Subjects With Metastatic or Inoperable Melanoma, MSI-H, dMMR or NSCLC
A Phase 1/2 study testing Fecal Microbial Transplantation by capsules in people with Melanoma Stage IV and Unresectable Melanoma, run by Ella Therapeutics Ltd at 1 site in Israel.
Trial summary
A Phase Ib trial to evaluate the safety and efficacy of Fecal Microbial Transplantation (FMT) in combination with Nivolumab in subjects with metastatic or inoperable melanoma, microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR) cancer, or Non-Small Cell Lung Cancer (NSCLC) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma Stage IV, Unresectable Melanoma, NSCLC Stage IV
- What is being tested?
- Fecal Microbial Transplantation by capsules
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Nov 2020to 1 Jul 2023
- Phase
- Phase 1/2
- 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
- Age and gender: 18 and older, all genders
- Signed written informed consent . Participants must be willing to participate in the study and provide written and signed informed consent (ICF) for the study.
- Participants must be willing and able to complete all study specific procedures and visits
- Diagnosis:
- For NSCLC patients Histologically or cytologically confirmed metastatic or locally advanced non-small cell lung cancer not amenable to curative treatment that have a confirmed progression on anti-PD-1/PDL1 therapy:
- Subjects may have had a maximum of one prior line of therapy after failure of anti-PD-1/ Programmed death-ligand 1 (PDL1) therapy Received a platinum based chemotherapy for non-small cell lung cancer; or, Subjects with a documented activating mutation {e.g., against epidermal growth factor receptor (EGFR), against rearranged anaplastic lymphoma kinase (ALK), Proto-oncogene tyrosine-protein kinase (ROS)} must have received the appropriate targeted therapy.
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- For Melanoma patients Histologically confirmed unresectable or metastatic melanoma not amenable to curative treatment that have a confirmed progression on anti-PD-1/PD-L1 therapy: a. Subjects may have had a maximum of one prior line of therapy after failure of anti-PD-1/PDL1 therapy b. Subjects with a documented B-Raf (BRAF) mutation must have received the appropriate targeted therapy
- For MSI-H/dMMR patients -Histologically confirmed MSI-H/dMMR metastatic solid tumors including the following indications: colorectal adenocarcinoma, gastric adenocarcinoma, esophageal adenocarcinoma, endometrial carcinoma, ovarian carcinoma, pancreatic ductal adenocarcinoma and urothelial carcinoma that had a confirmed progression on anti-PD-1/PD-L1-based therapy.
- Biopsies Patients must agree to study biopsies at two time points: a. Pretreatment and on treatment gut biopsies. b. Pretreatment and on treatment tumor biopsies.
- Measurable disease by RECIST v1.1.
- Patient status: a. Eastern Cooperative Oncology Group (ECOG) status of 0-1 b. Liver function: Total bilirubin ≤ 2 Upper limit of normal (ULN), Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) ≤ 2.5 ULN (or < 5 in case of present liver metastasis) c. Neutrophils ≥ 1,000/mm3, platelets ≥ 100,000/mm3, Hb>8 g/dL d. Serum creatinine ≤ 1.5 ULN e. International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5x ULN
- Pregnancy a. Negative urine or serum pregnancy test within 72 hours prior to receiving first dose of study procedure in women of childbearing potential. b. Use of an effective contraceptive method throughout the entire treatment period and up to 6 months after the completion of treatment in both males and females of child bearing potential.
Who cannot join
- Medical Conditions :
- 1.1 History of chronic or active colitis 1.2. Tumor involvement of the esophagus, stomach, small intestine or colo-rectum. Note: not applicable for patients with MSI-H or dMMR colorectal , gastric or esophageal adenocarcinoma 1.3. Has a current active or a past known additional malignancy within the last 5 years.
- 1.4. Has an active or a documented history of autoimmune disease that required treatment in the past 2 years.
- 1.5. Known food allergy to eggs, nuts, peanuts 1.6. Known allergy to neomycin,vancomycin or metronidazole 1.7. Pregnant or breastfeeding women 1.8. Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) 1.9 Has known history of or is positive for hepatitis B or Hepatitis C.
- Prior/Concomitant Therapy and medical procedure 2.1 Has ongoing immune-related adverse effects from previous immunotherapy treatments that are of Grade ≥2, excluding endocrine adverse effects 2.2 Immunosuppressive chronic treatments. Patients treated with Prednisone ≤10mg per day may be included.
- 2.3 Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with i.v. antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to the start of Day 1 2.4 Medical condition that requires chronic treatment with antibiotics 2.5 Vaccination with live vaccines within 28 days prior to start of Cycle 1, Day 1.
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- 2.6 Has received major surgery (within 28 days prior to the start of Cycle 1, Day 1), other than for diagnosis. Patient must have recovered from all surgery-related toxicities.
- 2.7 Patient has a known intolerance to anti-PD-L1 or anti-PD1.
- Prior/Concurrent Clinical Study Experience 3.1 Participation in another clinical trial with anti-neoplastic intervention up to 14 days prior to study entry
- Other Exclusions 4.1 Any other serious uncontrolled medical condition (including active bleeding or non-healing wound) 4.2 Has known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the study.
Trial locations and contacts
1 site in 1 country.
Israel1 site, 1 recruiting
- Recruiting
Sheba Medical Center
Ramat Gan
Meital Bar, Bar Meital <Meital.Bar@sheba.health.gov.il>
Nili Golan, Nili.Golan@sheba.health.gov.il
About this study
Official title: A Phase Ib Trial to Evaluate the Safety and Efficacy of Fecal Microbial Transplantation (FMT) in Combination With Nivolumab in Subjects With Metastatic or Inoperable Melanoma, Microsatellite Instability-high (MSI-H) or Mismatch-repair Deficient (dMMR) Cancer, or Non-Small Cell Lung Cancer (NSCLC)
A Phase Ib trial to evaluate the safety and efficacy of Fecal Microbial Transplantation (FMT) in combination with Nivolumab in subjects with metastatic or inoperable melanoma, microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR) cancer, or Non-Small Cell Lung Cancer (NSCLC)
Read the detailed description
This study is a Phase I single-center adaptive design study to evaluate the safety and efficacy of FMT in combination with Nivolumab for adult subjects with treatment-refractory or inoperable melanoma, MSH-H, dMMr or NSCLC.
FMT will be conducted with fecal capsules, originating from patients that have achieved a durable complete response with immune checkpoint inhibitors. The study will evaluate the safety and efficacy of the combination of FMT with Nivolumab, a human immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1 (anti PD-1) treatment and explore different biomarkers.
- Conditions
- Melanoma Stage IV, Unresectable Melanoma, NSCLC Stage IV
- Being tested
- Fecal Microbial Transplantation by capsules
- Medical subject headings
- Melanoma, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fecal Microbial Transplantation by capsulesBiological
Also called Nivolumab
Cohorts A and B - Patients will receive 30 oral capsules per administration for two consecutive days (Days 1-2) Cohort C - Patients will receive FMT via colonscopy (Day 1), followed the day after by adnistration of 12 oral capsules (Day 2)
Combination cycles: 6 combined cycles Q2W of FMT maintenance followed by treatment with anti-PD1. Anti-PD-1 will be administered at least one day and up to 3 days after the FMT.
Maintenance of FMT by oral capsules: 12 capsules per administration. Anti PD-1 therapy: A dose of 240 mg Nivolumab will be administrated by intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm | Experimental | Combination treatment: anti PD1 + FMT by capsules Receives: Biological: Fecal Microbial Transplantation by capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of FMT-related Adverse Events
Number of patients with adverse events that emerged post FMT. The AE severity grading scale for the NCI-CTCAE (v5.0) will be used for assessing AE severity
Measured: 3 years
Overall Response Rate (ORR)
Number of patients with objective responses divided by the total number of evaluable patients, according to imaging studies (RECIST 1.1) and iRECIST
Measured: 3 years
Secondary outcomes (6)
Changes in immune activation in the gut
Immune activation in gut is defined as a 20% or more increase in cluster of differentiation 68 (CD68) cell counts pre and post FMT
Measured: 3 years
Changes in immune activation in the tumor
Changes in the relative abundance of different immune cell population (such as the proportion of cluster of differentiation 8 (CD8) and T cell in the tumor pre and post FMT
Measured: 3 years
Progression-free survival (PFS)
Duration of progression free status evaluated according to imaging studies (RECIST 1.1) and iRECIST.
Measured: 3 years
To assess Overall survival (OS)
The proportion of patients remaining alive from initiation of study treatment until completion of two year follow-up from End of Treatment (EOT)
Measured: 3 years
To assess Duration of response (DoR)
Time from initial response to disease progression or death among patients who have experienced a Complete Response (CR) or Partial Response (PR) according to RECIST v1.1
Measured: 3 years
Incidence of immune related toxicities induced by anti-PD-1
Number and Grade of immune related Adverse events (irAE) reported that emerged post anti-PD1 treatment
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2020
- Study start1 Nov 2020
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Jul 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma Stage IVStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Stage I: Cohort A: Fifteen Melanoma patients will be treated with FMT capsules originating from 5 different donors. Cohort B: Two NSCLC patients will be treated with FMT capsules originating from 2 different donors. Cohort C: Three MSI-H or dMMR patients will be treated with FMT via colonoscopy and capsules combined with anti-PD-1 (Nivolumab). An interim analysis will be conducted following completion of recruitment of 15 patients. Based on the interim analysis, the abovementioned independent cohorts will be expanded to include additional patients as Stage II: Cohort A expansion will include 15 melanoma patients Cohort C expansion will include seven MSI-H or dMMR patients. Patients will be treated with FMT originating from selected donors, combined with anti-PD-1 (Nivolumab).
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ella Therapeutics Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Guy Ben-Betzalel, MD, Principal investigator, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04521075
- Sponsor's protocol ID
- 6735-19
- Status last verified
- Aug 2021
- First submitted
- 13 Aug 2020
- Last updated
- 16 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Trial to Evaluate the Safety and Efficacy of Fecal Microbial Transplantation (FMT) in Combination With Nivolumab in Subjects With Metastatic or Inoperable Melanoma, Microsatellite Instability-high (MSI-H) or Mismatch-repair Deficient (dMMR) Cancer, or Non-Small Cell Lung Cancer (NSCLC)
- ClinicalTrials.gov ID
- NCT04521075
- Acronym / sponsor ID
- 6735-19
- Conditions
- Melanoma Stage IV, Unresectable Melanoma, NSCLC Stage IV
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Ella Therapeutics LtdIndustry (pharma, biotech, devices)
- Study start
- 1 Nov 2020 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Jul 2023 (estimated)
- First posted
- 20 Aug 2020 (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.
A Phase Ib trial to evaluate the safety and efficacy of Fecal Microbial Transplantation (FMT) in combination with Nivolumab in subjects with metastatic or inoperable melanoma, microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR) cancer, or Non-Small Cell Lung Cancer (NSCLC)
Detailed description
This study is a Phase I single-center adaptive design study to evaluate the safety and efficacy of FMT in combination with Nivolumab for adult subjects with treatment-refractory or inoperable melanoma, MSH-H, dMMr or NSCLC.
FMT will be conducted with fecal capsules, originating from patients that have achieved a durable complete response with immune checkpoint inhibitors. The study will evaluate the safety and efficacy of the combination of FMT with Nivolumab, a human immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1 (anti PD-1) treatment and explore different biomarkers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Stage I: Cohort A: Fifteen Melanoma patients will be treated with FMT capsules originating from 5 different donors. Cohort B: Two NSCLC patients will be treated with FMT capsules originating from 2 different donors. Cohort C: Three MSI-H or dMMR patients will be treated with FMT via colonoscopy and capsules combined with anti-PD-1 (Nivolumab). An interim analysis will be conducted following completion of recruitment of 15 patients. Based on the interim analysis, the abovementioned independent cohorts will be expanded to include additional patients as Stage II: Cohort A expansion will include 15 melanoma patients Cohort C expansion will include seven MSI-H or dMMR patients. Patients will be treated with FMT originating from selected donors, combined with anti-PD-1 (Nivolumab).
| Arm | Type | Receives |
|---|---|---|
| Treatment Arm | Experimental | Biological: Fecal Microbial Transplantation by capsulesCombination treatment: anti PD1 + FMT by capsules |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age and gender: 18 and older, all genders
- Signed written informed consent . Participants must be willing to participate in the study and provide written and signed informed consent (ICF) for the study.
- Participants must be willing and able to complete all study specific procedures and visits
- Diagnosis:
- For NSCLC patients Histologically or cytologically confirmed metastatic or locally advanced non-small cell lung cancer not amenable to curative treatment that have a confirmed progression on anti-PD-1/PDL1 therapy:
Key exclusion criteria (10 listed)
- Medical Conditions :
- 1.1 History of chronic or active colitis 1.2. Tumor involvement of the esophagus, stomach, small intestine or colo-rectum. Note: not applicable for patients with MSI-H or dMMR colorectal , gastric or esophageal adenocarcinoma 1.3. Has a current active or a past known additional malignancy within the last 5 years.
- 1.4. Has an active or a documented history of autoimmune disease that required treatment in the past 2 years.
- 1.5. Known food allergy to eggs, nuts, peanuts 1.6. Known allergy to neomycin,vancomycin or metronidazole 1.7. Pregnant or breastfeeding women 1.8. Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) 1.9 Has known history of or is positive for hepatitis B or Hepatitis C.
- Prior/Concomitant Therapy and medical procedure 2.1 Has ongoing immune-related adverse effects from previous immunotherapy treatments that are of Grade ≥2, excluding endocrine adverse effects 2.2 Immunosuppressive chronic treatments. Patients treated with Prednisone ≤10mg per day may be included.
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 |
|---|---|---|
| Fecal Microbial Transplantation by capsulesAlso: NivolumabCohorts A and B - Patients will receive 30 oral capsules per administration for two consecutive days (Days 1-2) Cohort C - Patients will receive FMT via colonscopy (Day 1), followed the day after by adnistration of 12 oral capsules (Day 2) Combination cycles: 6 combined cycles Q2W of FMT maintenance followed by treatment with anti-PD1. Anti-PD-1 will be administered at least one day and up to 3 days after the FMT. Maintenance of FMT by oral capsules: 12 capsules per administration. Anti PD-1 therapy: A dose of 240 mg Nivolumab will be administrated by intravenous infusion. | Biological | Treatment Arm |
Primary outcome
Incidence of FMT-related Adverse Events
Time frame: 3 years
Number of patients with adverse events that emerged post FMT. The AE severity grading scale for the NCI-CTCAE (v5.0) will be used for assessing AE severity
Overall Response Rate (ORR)
Time frame: 3 years
Number of patients with objective responses divided by the total number of evaluable patients, according to imaging studies (RECIST 1.1) and iRECIST
6 secondary outcomes
Changes in immune activation in the gut
Time frame: 3 years
Changes in immune activation in the tumor
Time frame: 3 years
Progression-free survival (PFS)
Time frame: 3 years
To assess Overall survival (OS)
Time frame: 3 years
To assess Duration of response (DoR)
Time frame: 3 years
Incidence of immune related toxicities induced by anti-PD-1
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2021.
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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.
Guy Ben-Betzalel, MD principal investigator
Sheba Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Fecal Microbial Transplantation by capsules in people with Melanoma Stage IV and Unresectable Melanoma, run by Ella Therapeutics 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 12 inclusion and 10 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 16 Aug 2021. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Elizbeth Tarshish, Msc (+972-504048559, elizabeth@ellatherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of FMT-related Adverse Events (time frame: 3 years). The study lists 2 primary outcomes in all. 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 16 Aug 2021.