Study of MRx0518 and Avelumab in Patients With Urothelial Carcinoma

NCT05107427 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: MRx0518-004
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief 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 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.

Conditions

Urothelial Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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)

  Through study completion, an average of 1 year

• 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

  All patients after 6 months

Secondary Outcomes (6)

• Progression-free survival (PFS)

  Through study completion, an average of 1 year

• Objective response rate (ORR)

  Through study completion, an average of 1 year

• Objective progressive disease (PD)

  Through study completion, an average of 1 year

• Time to response

  Through study completion, an average of 1 year

• Overall survival (OS)

  Through study completion, an average of 1 year

Study Arms (1)

MRx0518 + Avelumab

EXPERIMENTAL

Subjects will receive 1 capsule of MRx0518 BID throughout the treatment period and IV infusion of Avelumab every 2 weeks in 4-week cycles

Drug: MRx0518; Biological: Avelumab 20 mg/mL Intravenous Solution (IV)

Interventions

MRx0518 DRUG

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.

MRx0518 + Avelumab

Avelumab 20 mg/mL Intravenous Solution (IV) BIOLOGICAL

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

Also known as: BAVENCIO ®, MSB0010718C

MRx0518 + Avelumab

Eligibility Criteria

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

You may qualify if:

• 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).
• 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:

You may not qualify if:

• 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.
• 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);

Sponsors & Collaborators

• 4D pharma plc: lead

Study Sites (3)

University of California Irvine

Irvine, California, 92697, United States

Location

University of Texas Southwestern

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

avelumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Amishi Y Shah, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 8, 2021
• First Posted: November 4, 2021
• Study Start: March 1, 2022
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2023
• Last Updated: April 18, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)