26 August 2020
4D pharma announces comprehensive clinical benefit data from Part A of combination trial of MRx0518 and Keytruda®
42% disease control rate exceeds predefined threshold for expansion
Leeds, UK, August 26, 2020 - 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, today announces the complete clinical benefit analysis from Part A of its Phase I/II clinical trial of Live Biotherapeutic candidate MRx0518 in combination with immune checkpoint inhibitor (ICI) Keytruda® (pembrolizumab), the anti-PD-1 therapy of MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, in heavily pre-treated patients with solid tumours.
In 12 patients with metastatic renal cell carcinoma (mRCC) and metastatic non-small cell lung cancer (mNSCLC), the combination of MRx0518 with KEYTRUDA achieved a disease control rate (DCR) of 42%, with five of 12 patients experiencing a clinically meaningful benefit from the combination. Three patients experienced partial responses (PR), defined as target tumour shrinkage of 30% or greater - an objective response rate (ORR) of 25%. MRx0518 in combination with KEYTRUDA induced durable stable disease (SD) of six months or greater in an additional two patients (17%). Median duration of treatment for the five patients experiencing clinical benefit is now 13.2 months, with four of these patients currently ongoing.
As previously reported, MRx0518 demonstrated a highly favourable safety profile, with no treatment-related serious adverse events (SAEs) or drug discontinuations and, importantly, no increase of immune-related adverse events (irAEs) commonly associated with ICI therapy.
Prof. Jaap Verweij, Emeritus Professor of Medical Oncology, at Erasmus University Medical Center in Rotterdam, the Netherlands, former chair of the Response Evaluation Criteria in Solid Tumors (RECIST) working group, and an advisor to the Company said, “Having been a clinical investigator on over 150 early stage trials with a wide variety of anti-cancer agents, I believe that these results are extremely encouraging, particularly given the novelty of the approach and the durability of clinical benefit observed.”
Dr Alex Stevenson, Chief Scientific Officer, 4D pharma, commented, “The disease control rate observed in part A of the study, at 42%, far exceeds the 10% threshold for success agreed with our partner MSD for the cohort expansion phase, boding well for the outcome of the ongoing Part B of the study. This is ground-breaking for the microbiome in immuno-oncology. Considering the advanced stage of disease of the patients in the study, end of line patients who have previously failed on a checkpoint inhibitor and have little to no remaining treatment options, these results are very promising.”
He added, “We believe that, while this is a small study, these efficacy and safety results in such a difficult-to-treat population are notable. To achieve these results while maintaining a very clean safety profile is to our knowledge unparalleled, and particularly significant in oncology where there is all too often the unfortunate trade-off between treatment and quality of life, and patients often elect to interrupt or stop treatment completely due to adverse side effects."
Following successful completion of the Part A safety phase, the Part B cohort expansion phase of the trial is enrolling at multiple sites, and will assess the clinical benefit of the combination of MRx0518 and KEYTRUDA in addition to safety, in up to 30 additional patients per tumour type. The study is open-label and 4D pharma expects to make periodic announcements on progress and updated results as appropriate.
The trial is enrolling heavily pre-treated metastatic patients with selected solid tumours refractory to ICIs. Eligible patients must have experienced at least stable disease on previous ICI therapy (as a monotherapy or combination) but eventually progressed, as confirmed by two radiological scans ≥4 weeks apart in the absence of rapid clinical progression and within 12 weeks of last dose of ICI. Patients are treated with 1 capsule of MRx0518 twice daily and pembrolizumab every 3 weeks for up to 35 cycles (approximately 2 years) or until disease progression. Tumour response is assessed every 9 weeks per the RECIST 1.1 criteria. The primary objective of Part B is to evaluate safety of the combination. Secondary objectives were to evaluate efficacy via overall response rate (ORR), duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS).
MRx0518 is 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 three 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 patients who have previously progressed on anti PD-1 therapies. The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA.MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer.
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 AEs or withdrawal of consent up to a maximum of 35 cycles of KEYTRUDA.
Part A was conducted in 12 patients and Part B will be conducted in up to 30 patients of each tumour type.
The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA.
For more information on the trial, see https://clinicaltrials.gov/ct2/show/NCT03637803.
Founded in February 2014, 4D pharma 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 six clinical studies in progress, namely a Phase II clinical study of BLAUTIX® in Irritable Bowel Syndrome (IBS), 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, a Phase I study of MRx0518 in patients with pancreatic cancer, a Phase I/II study of MRx-4DP0004 in asthma, and a Phase II study of MRx-4DP0004 in patients hospitalised with COVID-19. Preclinical-stage programs 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.
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