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Urothelial CarcinomaPhase 2AVENUNCT05107427

Study of MRx0518 and Avelumab in Patients With Urothelial Carcinoma

A Phase 2 study testing MRx0518 and Avelumab 20 mg/mL Intravenous Solution (IV) in people with Urothelial Carcinoma, run by 4D pharma plc at 3 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This is an open-label, switch maintenance study of MRx0518 and Avelumab in patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) whose disease did not progress after 4 to 6 cycles of first-line platinum-containing chemotherapy and who have residual measurable disease according to Response… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Urothelial Carcinoma
What is being tested?
MRx0518 and Avelumab 20 mg/mL Intravenous Solution (IV)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
3 sitesUnited States
Study dates
1 Mar 2022to Apr 2023
Phase
Phase 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 informed consent.
  • Age ≥18 years at the time of consent.
  • Histologically confirmed unresectable locally advanced or metastatic transitional cell carcinoma of the urothelium.
  • Documented Stage IV disease (per American Joint Committee on Cancer/International Union for Cancer Control Tumor Node Metastasis (TNM) system, 7th edition) (AJCC 2012) at the start of first-line chemotherapy.
  • Prior first-line chemotherapy consisting of at least 4 but not more than 6 cycles of gemcitabine + cisplatin and/or gemcitabine + carboplatin and/or dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) with last dose received no less than 4, and no more than 10 weeks prior to date of first study treatment dose.
  • No evidence of PD during or following first-line chemotherapy (ie, ongoing PR or SD per RECIST v1.1).
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  • At least 1 measurable lesion per RECIST v1.1 after completion of first-line chemotherapy.
  • Willing to undergo mandatory de novo tumor biopsies at baseline and Cycle 3 in the absence of existing biopsy material without intervening therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Adequate bone marrow function, including:
  • Absolute neutrophil count (ANC) ≥1500/mm^3 or ≥1.5 × 10^9/L;
  • Platelets ≥100,000/mm^3 or ≥100 × 10^9/L;
  • Hemoglobin ≥9 g/dL (may have been transfused).
  • Adequate renal function, defined as estimated creatinine clearance ≥30 mL/min (creatinine clearance should be calculated per institutional standard).
  • Adequate liver function, including:
  • Total serum bilirubin ≤1.5 × upper limit of normal (ULN);
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN, or, for patients with documented metastatic disease to the liver, AST, and ALT ≤5 × ULN.
  • Serum pregnancy test (for female of childbearing potential) negative at screening.
  • Female patients of childbearing potential who are, in the opinion of the investigator, sexually active and at risk of pregnancy, must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment.
  • Willing to follow protocol-specific contraceptive guidance for the duration of the study

Who cannot join

  • Persisting toxicity related to prior therapy NCI-CTCAE Grade >1) at the time of enrollment; however, alopecia, sensory neuropathy Grade ≤2 is acceptable; or other grade ≤2 AEs not constituting a safety risk based on the investigator's judgment are acceptable.
  • Prior immunotherapy with IL-2, interferon (IFN)-α, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
  • Prior adjuvant or neoadjuvant systemic therapy within 12 months of enrollment.
  • Known symptomatic central nervous system (CNS) metastases requiring steroids. Patients with previously diagnosed CNS metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable.
  • CR to the preceding platinum-based chemotherapy for locally advanced or metastatic disease received systemic antibiotics within 2 weeks prior to first dose.
  • Received systemic antibiotics within 2 weeks prior to first dose.
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  • Prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen for this study.
  • Female patients who are pregnant or breastfeeding.
  • Allergy to amoxicillin/clavulanic acid, erythromycin, and imipenem.
  • Known inability for oral intake of capsules.
  • Active infection requiring systemic therapy.
  • Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis, or uncontrolled asthma (ie, 3 or more features of asthma symptom control per the Global Initiative for Asthma 2015).
  • Known prior or suspected hypersensitivity to study medications or any component in their formulations.
  • Use of immunosuppressive medication within 7 days prior to first dose of study treatment, EXCEPT the following:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection);
  • System corticosteroids at physiologic doses ≤10 mg/day of prednisone or equivalent;
  • Steroids as premedication for hypersensitivity reactions (eg, computerized tomography [CT] scan premedication).
  • Diagnosis of prior immunodeficiency or organ transplant requiring immunosuppressive therapy.
  • Positive test for HIV infection or known AIDS.
  • Evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
  • Vaccination with live vaccines within 4 weeks prior to the first dose of study treatment and while on study is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines). Vaccination with approved COVID-19 vaccines is permitted any time prior to and/or during the study except the days of Avelumab administration.
  • Diagnosis of any other malignancy within 5 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast or cervix, low grade (Gleason ≤6) prostate cancer on surveillance without any plans for treatment intervention (eg, surgery, radiation, or castration), or prostate cancer that has been adequately treated with prostatectomy or radiotherapy and currently with no evidence of disease or symptoms.
  • Participating in other studies involving investigational drug(s) within 4 weeks prior to enrollment. Observational studies are permitted.
  • Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
  • Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication.
  • Patients who are investigational site staff members directly involved in the conduct of the study and their family members, or site staff members otherwise supervised by the investigator.
  • Other severe acute or chronic medical conditions including but not limited to colitis, inflammatory bowel disease, pneumonitis, and pulmonary fibrosis; psychiatric condition including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California Irvine

    Irvine, California, 92697

Other trials in United States

About this study

Official title: A Phase 2 Switch Maintenance Study of MRx0518 and Avelumab in Patients With Unresectable Locally Advanced or Metastatic Urothelial Carcinoma Who Did Not Progress on First-Line Platinum-Containing Chemotherapy

This is an open-label, switch maintenance study of MRx0518 and Avelumab in patients with unresectable locally advanced or metastatic urothelial carcinoma (UC) whose disease did not progress after 4 to 6 cycles of first-line platinum-containing chemotherapy and who have residual measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Up to 30 patients will be enrolled.

Patients enrolled in this study will be treated with IV Avelumab every 2 weeks and MRx0518 daily during the treatment period. Patients will receive the study treatment until disease progression (PD), patient withdrawal, or unacceptable toxicity.

Read the detailed description

Inclusion in the study must occur ≥4 but <10 weeks after the date of last dose of first-line chemotherapy. Post-chemotherapy confirmatory scan(s) for eligibility must be performed within 28 days prior to inclusion in the study to assess response status following first-line chemotherapy. Patients with ongoing partial response (PR) or stable disease (SD) (per RECIST v1.1) and who have measurable disease (per RECIST v1.1) are eligible for the study.

Being tested
MRx0518, Avelumab 20 mg/mL Intravenous Solution (IV)
Medical subject headings
Carcinoma, Transitional Cell

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.

  • Avelumab 20 mg/mL Intravenous Solution (IV)Biological

    Also called BAVENCIO ®, MSB0010718C

    Avelumab is an IV administered monoclonal antibody that blocks the interaction of programmed death ligand-1 (PD-L1) with its receptors PD-1 and B7.1 on T cells and antigen-presenting cells, and has been shown to activate adaptive and innate immune functions.

    The study dosing regimen is 800 mg (four 20mL vials of 20mg/mL solution) for IV infusion once every two weeks

Study groups in NCT05107427
Study groupRoleWhat they receive
MRx0518 + AvelumabExperimentalSubjects will receive 1 capsule of MRx0518 BID throughout the treatment period and IV infusion of Avelumab every 2 weeks in 4-week cycles
Receives: Drug: MRx0518; Biological: Avelumab 20 mg/mL Intravenous Solution (IV)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of MRx0518 and Avelumab combination treatment

    Safety of MRx0518 and Avelumab combination treatment assessed by adverse events (AEs) as graded by National Cancer Institute (NCI) Common Terminology (CTCAE V5.0)

    Measured: Through study completion, an average of 1 year

  2. Landmark PFS at 6 months from the date of first dose of study treatment for all patients

    Landmark PFS at 6 months from the date of first dose of study treatment for all patients. PFS events are death due to any cause or PD as determined by the investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Measured: All patients after 6 months

Secondary outcomes (6)

  1. Progression-free survival (PFS)

    PFS defined as the time from the date of first dose of study treatment until the earliest date of PD as determined by the investigator assessment of radiographic disease per RECIST v1.1 or death due to any cause, whichever occurs first

    Measured: Through study completion, an average of 1 year

  2. Objective response rate (ORR)

    ORR, defined as the percentage of patients having complete response (CR) or partial response (PR), as determined by investigator assessment of radiographic disease per RECIST v1.1.

    Measured: Through study completion, an average of 1 year

  3. Objective progressive disease (PD)

    Duration of response, defined as the time from the first partial response (PR) or complete response (CR) in this study to the date of first documented objective PD.

    Measured: Through study completion, an average of 1 year

  4. Time to response

    Time to response, defined as the time from first dose of study treatment to first documented objective tumor response of PR or better as determined by investigator assessment of radiographic disease per RECIST v1.1, which is subsequently confirmed.

    Measured: Through study completion, an average of 1 year

  5. Overall survival (OS)

    OS defined as the time from first dose of study treatment to the date of death due to any cause

    Measured: Through study completion, an average of 1 year

  6. Disease Control Rate (DCR)

    DCR, defined as the percentage of patients having CR, PR, or stable disease (SD) determined by investigator assessment of radiographic disease according to RECIST v1.1.

    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.

  1. First posted4 Nov 2021
  2. Study start1 Mar 2022
  3. Primary completionApr 2023 (estimated)
  4. Study completionApr 2023 (estimated)

Why it stopped: Sponsor unable to proceed

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05107427
Sponsor's protocol ID
MRx0518-004
Acronym
AVENU
Status last verified
Apr 2023
First submitted
8 Oct 2021
Last updated
18 Apr 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MRx0518 and Avelumab 20 mg/mL Intravenous Solution (IV) in people with Urothelial Carcinoma, run by 4D pharma plc at 3 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 20 inclusion and 27 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: withdrawn, as of the sponsor's last update on 18 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 phase mean?

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 withdrawn before enrolling participants, so there are no results.

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?

Safety of MRx0518 and Avelumab combination treatment (time frame: Through study completion, an average of 1 year). 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?

On the ClinicalTrials.gov record for NCT05107427.

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 18 Apr 2023.

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