OncologyPhase 1/2NCT03637803
Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors
A Phase 1/2 study testing MRx0518 and Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA] in people with Oncology and Solid Tumor, run by 4D pharma plc at 5 sites in United States.
Trial summary
This is an open label, safety and preliminary efficacy study of MRx0518 in combination with pembrolizumab in patients with solid tumours (non small cell lung cancer, renal cell carcinoma, bladder cancer or melanoma). Subjects will be treated with IV pembrolizumab every 3 weeks and 1 capsule twice daily of MRx0518. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Oncology, Solid Tumor, Non Small Cell Lung Cancer
- What is being tested?
- MRx0518 and Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 63 participants
- Where
- 5 sitesUnited States
- Study dates
- 10 Jan 2019to 8 May 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
- Willing and able to provide written informed consent/assent for the trial.
- ≥18 years of age on day of signing informed consent.
- Histological or cytological evidence of advanced and/or metastatic or recurrent NSCLC, renal cell carcinoma, bladder cancer or melanoma.
- At least one measurable lesion per RECIST v 1.1 criteria.
- Failure to respond or intolerance to standard therapy or for whom no appropriate therapies are known to provide clinical benefit (per the judgement of the Investigator).
- 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/PD-L1 inhibitor treatment progression is defined by meeting all of the following criteria:
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- 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.
- Have adequate organ function
- Be willing to provide archival tissue
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Female subjects of childbearing potential should have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for ≥2 years.
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 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
- Subjects who failed to show any response to initial treatment with PD-1/PD-L1 inhibitor (i.e. no Response or no Stable Disease).
- Has active brain metastases or leptomeningeal disease. Subjects with asymptomatic CNS metastases which have been stable (defined as without evidence of progression by MRI for at least 28 days prior to initiation of therapy and any neurologic symptoms have returned to baseline) following treatment with surgery or radiation therapy are allowed.
- Prior solid organ or hematologic transplant.
- Treatment-related immune-mediated (or immune related) AEs from 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 treated with chemotherapy, immunotherapy, biologic therapy, or other investigational agent within <5 times the half-life of the agent or <21 days (whichever is shorter) of starting study drug. Continuation of hormone replacement therapy is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a GnRH agonist), ovarian, or breast cancer are not exclusionary.
- Subjects treated with tyrosine kinase inhibitor therapy or completed palliative radiotherapy <14 days from initiation of therapy.
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- Comorbidity requiring corticosteroid therapy (>10mg prednisone/day or equivalent) within 7 days of starting experimental therapy. 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 or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder.
- Significant cardiac dysfunction, 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 in 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
- Has a serious active infection requiring systemic therapy
- Subjects who have completed a course of antibiotics within the two weeks prior to dosing
- Has 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 planned treatment start
- Known HIV infection, or active infection with hepatitis A, B or C
- Has a history of (non-infectious) pneumonitis that required steroids or has current active pneumonitis
- Known additional malignancy either progressing r 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
- Subjects who are allergic to amoxicillin/clavulanic acid, erythromycin and imipenem
- 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
- Has a known inability for oral intake of capsules
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Houston Methodist Cancer Center
Houston, Texas, 77030
MD Anderson Cancer Center
Houston, Texas, 77030
University of Kansas Medical Center
Kansas City, Kansas, 66160
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Summit Cancer Center
Spokane, Washington, 99208
About this study
Official title: A Phase I/II Open Label, Safety And Preliminary Efficacy Study of MRx0518 In Combination With Pembrolizumab In Patients With Advanced Malignancies Who Have Progressed On PD-1/PD-L1 Inhibitors
This is an open label, safety and preliminary efficacy study of MRx0518 in combination with pembrolizumab in patients with solid tumours (non small cell lung cancer, renal cell carcinoma, bladder cancer or melanoma).
Subjects will be treated with IV pembrolizumab every 3 weeks and 1 capsule twice daily of MRx0518. Treatment will continue as long as clinically relevant, until disease progression, unacceptable AEs or withdrawal of consent up to a maximum of 35 cycles (approx. 2 years).
- Conditions
- Oncology, Solid Tumor, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Melanoma, Bladder Cancer
- Being tested
- MRx0518, Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]
- Keywords
- MK-3475, pembrolizumab, MRx0518, PD-1 Inhibitor, Oncology, Live Biotherapeutic Product
- Medical subject headings
- Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Renal Cell, Melanoma, Urinary Bladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRx0518Drug
MRx0518 is a live biotherapeutic product consisting of a lyophilised formulation of a proprietary strain of bacterium. The study dosing regimen is one capsule two times per day for the duration of the treatment period.
Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]Drug
Also called MK3475, Pembrolizumab, Keytruda
Pembrolizumab is a potent humanised immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD1) receptor , thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). The study dosing regimen is 200mg (two 4ml vials of 25mg/ml solution) for IV infusion once every three weeks.
| Study group | Role | What they receive |
|---|---|---|
| MRx0518 with pembrolizumab | Experimental | Subjects will receive IV infusion of pembrolizumab once every 3 weeks until disease progression, unacceptable AEs or withdrawal of consent up to a maximum of 35 cycles (approx. 2 years). Starting on the day of first pembrolizumab dose, subjects will take one capsule of MR0518 twice daily until the end of the treatment period. Receives: Drug: MRx0518; Drug: Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: To assess the safety and tolerability of MRx0518 in combination with pembrolizumab through the collection of adverse events
Adverse events will be assessed as per CTCAE v4
Measured: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Part B: To assess safety and tolerability of MRx0518 in combination with pembrolizumab through the collection of adverse events
Adverse events will be assessed as per CTCAE v4
Measured: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Part B: To assess the clinical benefit of MRx0518 in combination with pembrolizumab
To determine preliminary evidence of anti-tumor activity
Measured: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Secondary outcomes (1)
Antitumour effect
Antitumour effect is assessed through tumour imaging and measurement of lesions per RECIST and iRECIST (ORR, DOR, DCR, PFS)
Measured: Baseline and every 3 weeks until treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2018
- Study start10 Jan 2019
- Primary completion8 May 2023
- Study completion8 May 2023
Why it stopped: Sponsor insolvency
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for OncologyStudies 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
- Masking
- None (open label)
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- 4D pharma plc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Shubham Pant, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03637803
- Sponsor's protocol ID
- MRx0518-I-002
- Other IDs
- Keynote MK3475-823
- Status last verified
- May 2023
- First submitted
- 3 Aug 2018
- Last updated
- 1 Jun 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Open Label, Safety And Preliminary Efficacy Study of MRx0518 In Combination With Pembrolizumab In Patients With Advanced Malignancies Who Have Progressed On PD-1/PD-L1 Inhibitors
- ClinicalTrials.gov ID
- NCT03637803
- Acronym / sponsor ID
- MRx0518-I-002
- Conditions
- Oncology, Solid Tumor, Non Small Cell Lung Cancer, Renal Cell Carcinoma, Melanoma, Bladder Cancer
- Keywords
- MK-3475, pembrolizumab, MRx0518, PD-1 Inhibitor, Oncology, Live Biotherapeutic Product
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor insolvency
- Enrolment
- 63 participants (actual)
- Lead sponsor
- 4D pharma plcIndustry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 10 Jan 2019 (actual)
- Primary completion
- 8 May 2023 (actual)
- Study completion
- 8 May 2023 (actual)
- First posted
- 20 Aug 2018 (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.
This is an open label, safety and preliminary efficacy study of MRx0518 in combination with pembrolizumab in patients with solid tumours (non small cell lung cancer, renal cell carcinoma, bladder cancer or melanoma).
Subjects will be treated with IV pembrolizumab every 3 weeks and 1 capsule twice daily of MRx0518. Treatment will continue as long as clinically relevant, until disease progression, unacceptable AEs or withdrawal of consent up to a maximum of 35 cycles (approx. 2 years).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MRx0518 with pembrolizumab | Experimental | Drug: MRx0518, Drug: Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]Subjects will receive IV infusion of pembrolizumab once every 3 weeks until disease progression, unacceptable AEs or withdrawal of consent up to a maximum of 35 cycles (approx. 2 years). Starting on the day of first pembrolizumab dose, subjects will take one capsule of MR0518 twice daily until the end of the treatment period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Willing and able to provide written informed consent/assent for the trial.
- ≥18 years of age on day of signing informed consent.
- Histological or cytological evidence of advanced and/or metastatic or recurrent NSCLC, renal cell carcinoma, bladder cancer or melanoma.
- At least one measurable lesion per RECIST v 1.1 criteria.
- Failure to respond or intolerance to standard therapy or for whom no appropriate therapies are known to provide clinical benefit (per the judgement of the Investigator).
Key exclusion criteria (21 listed)
- Subjects who failed to show any response to initial treatment with PD-1/PD-L1 inhibitor (i.e. no Response or no Stable Disease).
- Has active brain metastases or leptomeningeal disease. Subjects with asymptomatic CNS metastases which have been stable (defined as without evidence of progression by MRI for at least 28 days prior to initiation of therapy and any neurologic symptoms have returned to baseline) following treatment with surgery or radiation therapy are allowed.
- Prior solid organ or hematologic transplant.
- Treatment-related immune-mediated (or immune related) AEs from 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 treated with chemotherapy, immunotherapy, biologic therapy, or other investigational agent within <5 times the half-life of the agent or <21 days (whichever is shorter) of starting study drug. Continuation of hormone replacement therapy is permitted. Stable regimens of hormonal therapy i.e. for prostate cancer (e.g. leuprolide, a GnRH agonist), ovarian, or breast cancer are not exclusionary.
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 |
|---|---|---|
| MRx0518MRx0518 is a live biotherapeutic product consisting of a lyophilised formulation of a proprietary strain of bacterium. The study dosing regimen is one capsule two times per day for the duration of the treatment period. | Drug | MRx0518 with pembrolizumab |
| Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]Also: MK3475, Pembrolizumab, KeytrudaPembrolizumab is a potent humanised immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD1) receptor , thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). The study dosing regimen is 200mg (two 4ml vials of 25mg/ml solution) for IV infusion once every three weeks. | Drug | MRx0518 with pembrolizumab |
Primary outcome
Part A: To assess the safety and tolerability of MRx0518 in combination with pembrolizumab through the collection of adverse events
Time frame: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Adverse events will be assessed as per CTCAE v4
Part B: To assess safety and tolerability of MRx0518 in combination with pembrolizumab through the collection of adverse events
Time frame: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Adverse events will be assessed as per CTCAE v4
Part B: To assess the clinical benefit of MRx0518 in combination with pembrolizumab
Time frame: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
To determine preliminary evidence of anti-tumor activity
1 secondary outcome
Antitumour effect
Time frame: Baseline and every 3 weeks until treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Results and safety
The study was stopped early (reason given: Sponsor insolvency). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2023.
- 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.
Shubham Pant, MD principal investigator
M.D. Anderson Cancer Center
5 sites 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 MRx0518 and Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA] in people with Oncology and Solid Tumor, run by 4D pharma plc at 5 sites in United States.
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 15 inclusion and 21 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: stopped early, as of the sponsor's last update on 1 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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?
The study was stopped early (reason given: Sponsor insolvency). 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?
Part A: To assess the safety and tolerability of MRx0518 in combination with pembrolizumab through the collection of adverse events (time frame: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)). The study lists 3 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 1 Jun 2023.