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BRIEF TITLE: 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

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


  • Org Study ID: MRx0518-I-002
  • Secondary ID: Keynote MK3475-823
  • NCT ID: NCT03637803
  • NCT Alias:
  • Sponsor: 4D pharma plc - Industry
  • Source: 4D pharma plc

Brief Summary

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).

Overal Status Start Date Phase Study Type
Recruiting January 10, 2019 Phase 1/Phase 2 Interventional

Primary Outcomes:

Primary Outcome 1 - Measure: Part A: To assess the safety and tolerability of MRx0518 in combination with pembrolizumab through the collection of adverse events

Primary Outcome 1 - Time Frame: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)

Primary Outcome 2 - Measure: Part B: To assess safety and tolerability of MRx0518 in combination with pembrolizumab through the collection of adverse events

Primary Outcome 2 - Time Frame: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)

Primary Outcome 3 - Measure: Part B: To assess the clinical benefit of MRx0518 in combination with pembrolizumab

Primary Outcome 3 - Time Frame: Baseline to treatment discontinuation up to a maximum of 35 treatment cycles (one cycle = 21 days)

Condition:

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

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/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:

1. Has received at least 2 doses of a PD-1/PD-L1 inhibitor.

2. 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.

3. 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.

Exclusion Criteria:

- 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.

- 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
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Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Official Information

Name: Shubham Pant, MD

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Clinical Operations

Phone: +441138950130

Email: clinicaltrials@4dpharmaplc.com

Location

Facility Status Contact
MD Anderson Cancer Center
Houston, Texas 77030
United States
Recruiting Shubham Pant, MD