Clinical Trials /

Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors

NCT03637803

Description:

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).

Related Conditions:
  • Bladder Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: MRx0518 and Pembrolizumab Combination 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 Inhibitors

Clinical Trial IDs

  • ORG STUDY ID: MRx0518-I-002
  • SECONDARY ID: Keynote MK3475-823
  • NCT ID: NCT03637803

Conditions

  • Oncology
  • Solid Tumor
  • Non Small Cell Lung Cancer
  • Renal Cell Carcinoma
  • Melanoma
  • Bladder Cancer

Interventions

DrugSynonymsArms
MRx0518MRx0518 with pembrolizumab
Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]MK3475, Pembrolizumab, KeytrudaMRx0518 with pembrolizumab

Purpose

This is a single center, 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).

Trial Arms

NameTypeDescriptionInterventions
MRx0518 with pembrolizumabExperimentalSubjects 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.
  • MRx0518
  • Pembrolizumab 25 MG/1 ML Intravenous Solution [KEYTRUDA]

Eligibility Criteria

        Inclusion Criteria:

          -  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 inhibitor administered either
             as monotherapy, or in combination with other checkpoint inhibitors or other therapies.
             PD-1 inhibitor treatment progression is defined by meeting all of the following
             criteria:

               1. Has received at least 2 doses of a PD-1 inhibitor.

               2. Has demonstrated disease progression after PD-1 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.

               3. Progressive disease has been documented within 12 weeks from the last dose of a
                  PD-1 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.

        Exclusion Criteria:

          -  Subjects who failed to show any response to initial treatment with PD-1 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.

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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)
Safety Issue:
Description:Adverse events will be assessed as per CTCAE v4

Secondary Outcome Measures

Measure:Antitumour effect
Time Frame:Baseline and every 3 weeks until treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)
Safety Issue:
Description:Antitumour effect is assessed through tumour imaging and measurement of lesions per RECIST and iRECIST (ORR, DOR, DCR, PFS)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:4D pharma plc

Trial Keywords

  • MK-3475
  • pembrolizumab
  • MRx0518
  • PD-1 Inhibitor
  • Oncology
  • Live Biotherapeutic Product

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