On February 3, 2021 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs) – a novel class of drug derived from the microbiome, reported progress on activities in its development program for lead immuno-oncology single strain Live Biotherapeutic candidate MRx0518 (Press release, 4d Pharma, FEB 3, 2021, View Source [SID1234574576]).
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"4D pharma has continued to make excellent progress with the MRx0518 development program on multiple fronts. We have generated additional safety and efficacy data, building on the positive data from both the monotherapy and KEYTRUDA combination studies last year. This clinical and development progress has been achieved in spite of the headwinds of COVID-19," said Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma. "As 4D pharma extends its leading position in this exciting and rapidly maturing field, we see the next 12 months as being instrumental for the space. We look forward to generating more clinical data from our ongoing studies of MRx0518 in multiple different tumor types and treatment settings. This will support 4D pharma’s continued productive engagement with regulatory authorities to develop the clinical strategy to bring this novel therapeutic to patients suffering from a range of cancers."
MRx0518 in Combination with KEYTRUDA
MRx0518 is in an ongoing Phase I/II clinical trial in combination with immune checkpoint inhibitor (ICI) Keytruda (pembrolizumab), MSD’s anti-PD-1 therapy, in patients with advanced malignancies who have previously progressed on ICI therapy. This study is comprised of two parts – Part A, an initial safety phase assessing dose-limiting toxicities of the combination, and the Part B cohort expansion phase to assess clinical benefit in addition to safety. In May 2020 the successful completion of Part A and initiation of Part B was announced.
24 additional patients across five active US sites have now been treated in Part B of this ongoing study. The safety review following the first Part B cohort of 10 renal cell carcinoma (RCC) patients has been completed indicating no dose limiting toxicities. A total of 12 patients with RCC, nine patients with non-small cell lung cancer (NSCLC) and three bladder cancer patients have been enrolled in Part B to date. Recruitment will continue up to a total of 30 patients in each of these indications.
Target tumor reductions in Part B patients have been observed as patients reach the first scheduled restaging timepoint (nine weeks). These include the first signals of anti-tumor activity for the combination in bladder cancer, adding to the previously reported activity in RCC and NSCLC in patients in Part A.
Three Part A patients with RCC and NSCLC that were previously reported to have experienced clinical benefit continue on the study. Two of these patients have now been treated for over 18 months and have had further target tumor reductions or extended disease control since the last update. Efficacy of the combination continues to be evaluated on an ongoing basis.
Following the positive results of Part A in RCC and NSCLC, the new tumor cohorts added to Part B of the study are now open to recruitment. Patients with advanced malignancies resistant to ICI therapy, including triple-negative breast cancer, head and neck squamous cell carcinoma and microsatellite instability-high/mismatch repair deficient cancers, are now eligible for inclusion. Enrolment for the trial is expected to complete in Q4 2021.
MRx0518 with Radiation in Pancreatic Cancer
Five patients are now enrolled in this Phase I trial. The study is designed to evaluate safety and efficacy in 15 patients receiving treatment with MRx0518 and hypofractionated radiation prior to surgery for pancreatic cancer. This study will generate valuable data to assess the relationship between systemic and tumor biomarkers, as well as clinical outcomes. Study treatment is well tolerated to date. Enrolment continues and we anticipate receiving initial data from this clinical trial in 2021.
MRx0518 in Neoadjuvant Setting Monotherapy
The previously reported 17 patients in the completed Part A of this Phase I study continue in the follow up phase for survival outcomes. Biomarker and safety data from the study were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting 2020, demonstrating systemic immune and tumor microenvironment modulation following two to four weeks of treatment with MRx0518. Additional biomarker analyses are underway to further investigate the immune response induced by MRx0518. These additional results may inform an optimization of Part B of this study.
About MRx0518
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 tumors. It is currently being evaluated in three clinical trials in cancer patients. MRx0518-I-001 (NCT03934827) is a neoadjuvant monotherapy study in a variety of solid tumors and is being conducted at Imperial College (London, UK). MRx0518-I-002 (NCT03637803) 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 (NCT04193904) is in combination with preoperative radiotherapy in resectable pancreatic cancer.