LEEDS, England, Nov. 6, 2019 /PRNewswire/ -- 4D pharma plc (AIM:
DDDD), a clinical-stage pharmaceutical company leading the
development of Live Biotherapeutics, today announced preliminary
safety and clinical observations from an ongoing Phase I/II
clinical trial, in collaboration with MSD, a tradename of Merck
& Co., Inc., Kenilworth, NJ,
USA, to evaluate its lead oncology candidate, MRx0518, in
combination with MSD's anti-PD-1 therapy KEYTRUDA®
(pembrolizumab); in patients with advanced malignancies who
have previously responded and whose disease has then progressed on
PD-1/PD-L1 inhibitors. These are the first observations from an
oncology study in man involving a Live Biotherapeutic Product.
Key observations:
- Initial data from the first six patients shows MRx0518 and
KEYTRUDA® combination is well tolerated
- Induction of clinically relevant response in two out of six
patients with prior progressive disease
- Three patients withdrawn for disease related reasons (two
following diagnosis of progressive disease and one due to a disease
related adverse event)
The Phase I/II study is an open label study to evaluate the
safety and preliminary efficacy of MRx0518 and KEYTRUDA® in
patients with renal cell carcinoma (RCC), melanoma, non-small cell
lung cancer (NSCLC) and bladder cancer who have developed
resistance to PD-1/PD-L1 inhibitors. In preclinical studies,
MRx0518 has previously shown significant efficacy as a monotherapy
and as a combination treatment with checkpoint therapy. MRx0518 has
also been shown to be a potent immunostimulant and capable of
increasing the number of tumour infiltrating lymphocytes (TILs)
associated with an anti-cancer effect in preclinical cancer models.
Higher numbers of such TILs are generally considered to be a
positive prognostic indicator for the clinical outcome of
checkpoint therapies, such as KEYTRUDA®.
Whilst checkpoint therapies have emerged as potent anti-cancer
treatments, they are not effective in all patients and those who do
respond can develop resistance over time, leading to a loss of
efficacy and disease progression. The mode of action of MRx0518 has
the potential to reactivate the efficacy of checkpoint therapies
and this study has been designed to investigate this effect in
patients with advanced metastatic disease.
Eligible patients in the Phase I/II study must have progressive
disease, confirmed by two restaging scans, prior to entry into the
study. Part A of the study is intended to enrol 12 patients with
the primary outcome being to measure safety and tolerability. Part
A is carried out over three weeks and patients receive one cycle of
KEYTRUDA®, with MRx0518 being taken orally twice a day ('bid').
Following completion of the first cycle, patients are eligible to
remain on the drug combination for up to thirty-five cycles of
KEYTRUDA® (approximately two years), or until disease progression
occurs. Patients routinely have restaging scans every nine weeks.
Further information on the study is included at the foot of this
announcement.
Clinical observations from the first six patients in part A
include:
- Two patients have shown a partial response (according to the
RECIST v1.1 criteria1) with evidence of tumour shrinkage
and remain on study (with one patient being on study for over six
months)
- One additional patient has disease that is stable and remains
on study
- Two patients were withdrawn from the study due to progressive
disease
- One patient was withdrawn due to a disease-related serious
adverse event prior to the restaging scan
- The only patient currently assessed for tumour biomarkers
showed evidence of increased TIL following treatment (consent for
biomarker assessment is optional)
- No drug related serious adverse events have been noted.
Chief Scientific Officer of 4D, Dr. Alex
Stevenson, said: "We are very encouraged by these early
signals of activity for the MRx0518 and KEYTRUDA® combination in
patients with advanced disease. One third of patients who had
previously stopped responding to PD-1 inhibitors and had
progressive disease have now demonstrated a clinical benefit. There
is also an initial signal in one patient suggesting that treatment
is able to increase the number of tumour infiltrating lymphocytes
in a clinical setting, which is consistent with our preclinical
findings. Although more work will be required to establish the
robustness of the responses observed and their frequency in a
larger number of patients, we are pleased to be able to report
these initial results – the first from an oncology study involving
a Live Biotherapeutic Product. The open label study is ongoing and
we will be reviewing data on a continual basis to optimise our
future development strategy for MRx0518 in these indications.
"These initial findings further support our continued investment
into our oncology franchise. We plan to take MRx0518 into
additional clinical studies involving different tumour types and
settings, either in combination or as a monotherapy. The next study
with MRx0518, in combination with radiotherapy in pancreatic
cancer, is planned to commence at MD Anderson before the end of the
year. In addition, we continue to develop new Live Biotherapeutic
candidates, with distinct modes of action, for oncology
applications. The first of these, MRx1299, is currently in GMP
manufacturing development."
Notes:
1 Response Evaluation Criteria in Solid
Tumours
This announcement contains inside information as defined in
Article 7 of the Market Abuse Regulation No. 596/2014 ("MAR"). The
person responsible for making this announcement for the Company is
Duncan Peyton. Upon the publication
of this announcement, this inside information is now considered to
be in the public domain.
About 4D
Founded in February 2014, 4D is a
world leader in the development of Live Biotherapeutics, a novel
and emerging class of drugs, defined by the FDA as biological
products that contain a live organism, such as a bacterium, that is
applicable to the prevention, treatment or cure of a disease. 4D
has developed a proprietary platform, MicroRx®, that rationally
identifies Live Biotherapeutics based on a deep understanding of
function and mechanism. 4D's Live Biotherapeutic Products are
orally delivered single strains of bacteria that are naturally
found in the healthy human gut. The Company has four clinical
studies in progress, namely a Phase II clinical study of BLAUTIX®
in Irritable Bowel Syndrome, a Phase I/II study of MRx0518 in
combination with KEYTRUDA® (pembrolizumab) in solid tumours, a
Phase I study of MRx0518 in a neoadjuvant setting for patients with
solid tumours and a Phase I/II study of MRx-4DP0004 in asthma.
Preclinical-stage programmes include candidates for CNS disease
such as Parkinson's disease and other neurodegenerative conditions.
The Company has a research collaboration with MSD, a tradename of
Merck & Co., Inc., Kenilworth,
NJ, USA, to discover and develop Live Biotherapeutics for
vaccines.
For more information, refer to
https://www.4dpharmaplc.com.
About MRx0518
MRx0518 is a single strain Live Biotherapeutic Product in
development for the treatment of cancer. It is delivered as an oral
capsule and stimulates the body's immune system, directing it to
produce cytokines and immune cells that are known to attack
tumours. It is currently being evaluated in two clinical trials in
cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy study
in a variety of solid tumours and is being conducted at Imperial
College (London, UK).
MRx0518-I-002 is in combination with KEYTRUDA® (pembrolizumab) in
collaboration with MSD, a tradename of Merck & Co., Inc.,
Kenilworth, NJ, USA.
About MRx0518-I-002 clinical trial
MRx0518-I-002 (NCT03637803) is a Phase I/II open label, safety
and preliminary efficacy study of MRx0518 in combination with
KEYTRUDA® (pembrolizumab) in patients with solid tumours (non-small
cell lung cancer, renal cell carcinoma, bladder cancer or melanoma)
who have previously progressed on anti PD-1/PD-L1 therapy. Subjects
are treated with intravenous KEYTRUDA® every three weeks and one
capsule twice daily of MRx0518. Treatment continues as long as
clinically relevant, until disease progression, unacceptable
adverse events or withdrawal of consent up to a maximum of 35
cycles of KEYTRUDA®.
Part A is being conducted in 12 patients (of any of the four
tumour types) and Part B will be conducted in up to 30 patients of
each tumour type, giving an overall total of up to 132
patients.