4D Pharma: successful completion of immuno-oncology study safety phase

Leeds, UK, May 11, 2020 - 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, today announces successful completion of Part A of a Phase I/II clinical trial of MRx0518 in combination with immune checkpoint inhibitor Keytruda(R) (pembrolizumab). Part A of the study evaluated the therapeutic combination in patients with advanced solid tumors who had previously shown an initial clinical benefit to PD-1/PD-L1 immune checkpoint inhibitors, but had subsequently developed secondary resistance and progressive disease.

The safety review committee for the study has evaluated data collected during the Dose Limiting Toxicity (DLT) period of the trial, the first cycle of treatment for the first 12 patients. The committee determined that it is safe to proceed to Part B of the study. Part B of the study has now commenced and will assess clinical benefit and safety, enrolling up to an additional 30 patients per tumor type cohort (up to a total of 120). Enrolment will be expanded to additional trial locations and sites. The study is open label and an update on progress is anticipated later in the year.

Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma, commented: “As with all of 4D pharma’s Live Biotherapeutics targeting a range of conditions, a good safety profile for MRx0518 was expected. It is important that this has been confirmed in Part A of this study in combination with a PD-1 immune checkpoint inhibitor. Commencing Part B of the study and expanding enrolment will enable us to build on the very encouraging preliminary signals of efficacy we have seen. These initial results indicate the potential for MRx0518 to be a game-changing immunotherapy for this particularly difficult-to-treat patient population for which all other therapeutic options have been exhausted.”

Dr. Jean-Pierre Bizzari, chair of the New Drug Advisory committee of the EORTC[1] and formerly Executive Vice-President and Head of Clinical Oncology Development at Celgene, commented: "The data from Part A of the study are very encouraging and quite promising, with the drug combination exhibiting an excellent safety profile and early signs of clinical benefit in heavily pre-treated patients with advanced metastatic disease. Further studies are warranted and I look forward to working with 4D in evaluating this treatment in a larger population of patients in Part B of the study”.

4D pharma previously reported positive interim clinical observations from Part A, in which three of the first six patients enrolled achieved a clinical benefit (complete response, partial response, or stable disease for six months or more), evidence of increased tumor-infiltrating lymphocytes (TILs) following treatment, and no drug related serious adverse events. These patients continue to show clinical benefit and have now been on study for between nine and twelve months. Further details on these patients, including treatment histories and the magnitude of responses, were presented at Chardan’s 2nd Annual Microbiome Medicines Summit in March (www.4dpharmaplc.com).

[1] The European Organisation for Research and Treatment of Cancer 

About MRx0518

MRx0518, a product of 4D's discovery platform MicroRx(R), is a single strain Live Biotherapeutic Product (LBP) 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 tumors.

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 tumors and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA(R) (pembrolizumab) in collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is a study in combination with radiotherapy in patients with 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(R) (pembrolizumab) in patients with solid tumors (non-small cell lung cancer, renal cell carcinoma, bladder cancer or melanoma) who have previously shown initial clinical benefit on anti PD-1/PD-L1 therapy, but subsequently developed progressive disease  Subjects are treated with intravenous KEYTRUDA(R) 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 (of any of the four tumor types) and Part B will be conducted in up to 30 patients of each tumor type, giving an overall total of up to 132 patients.

This study is being carried out at The University of Texas MD Anderson Cancer Center, Houston, USA, in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA. 

About 4D

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 five clinical studies in progress, namely a Phase II clinical study of BLAUTIX(R) in Irritable Bowel Syndrome (IBS), a Phase I/II study of MRx0518 in combination with KEYTRUDA(R) (pembrolizumab) in solid tumors, a Phase I study of MRx0518 in a neoadjuvant setting for patients with solid tumors, a Phase I study of MRx0518 in patients with pancreatic cancer and a Phase I/II study of MRx-4DP0004 in asthma. 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.