On March 17, 2020 4D pharma plc (AIM: DDDD), a pharmaceutical company leading the development of Live Biotherapeutics, reported an update on the previously reported interim data from an ongoing phase I/II clinical trial, in collaboration with MSD, a tradename of Merck & Co., Inc., Kenilworth, NJ, USA, to evaluate 4D pharma’s 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 (Press release, 4d Pharma, MAR 17, 2020, View Source [SID1234555662]).

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The additional data has been presented to delegates of Chardan’s virtual 2nd Annual Microbiome Medicines Summit, on March 16, 2020. The data was presented by Duncan Peyton, CEO and Alex Stevenson, CSO, 4D pharma. The presentation provides additional detail on headline interim results from the phase I/II clinical trial announced on November 6, 2019. The trial is being conducted, and data compiled at MD Anderson, University of Texas, US.

The data is the first global clinical confirmation of a live biotherapeutic product (LBP) initiating a response in cancer patients. The patients in the live biotherapeutic clinical trial had all previously received multiple lines of treatment with little efficacy, exhausting all currently approved treatment options. 4D pharma believes that the data provide evidence that adding the Company’s product, MRx0518, to the checkpoint inhibitor treatment regimen can induce tumour responses in patients who have previously become refractory to these therapies. 4D believes that, if demonstrated in larger studies, the addition of MRx0518 to checkpoint therapy will enable approved checkpoint inhibitors to work more effectively, for a longer duration, and in a wider patient population.

The phase I/II 4D pharma study is an open label trial 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. Checkpoint therapies, whilst capable of producing durable anti-tumour responses, are not effective in all patients. In addition, those who do respond can develop resistance over time, leading to disease progression. The study has been designed to investigate this effect in patients with advanced metastatic disease.

Clinical observations from the first six patients in part A were presented, including:

Two partial responses (PR) with evidence of tumor shrinkage who remain on study (one patient for over 10 months)
One patient with stable disease (SD), remains on study for over eight months
Evidence of increased tumor-infiltrating lymphocytes (TILs) following treatment
No drug related serious adverse events
Specifically, one stage IV NSCLC patient had received seven lines of therapy over nearly three years with little response. In this patient the combination of MRx0518 + KEYTRUDA achieved an overall 51% reduction in target tumors at last assessment. The patient has now been on drug for 41 weeks.

"The further interim data from the Phase I/II trial provide significant potential for fresh treatment options for oncology patients that have exhausted all other currently approved therapies," said Duncan Peyton, CEO, 4D pharma.

He added: "4D pharma is now delivering the first global clinical evidence of the therapeutic potential of oral live biotherapeutics in cancer. This confirms the significant impact of microbiome immuno-oncology to the pharmaceutical industry in providing additional treatments for patients with underserved needs and little available therapeutic options. This clinical validation of live biotherapeutics to impact diseases external to the gut significantly supports our wider clinical pipeline in other areas such as neurodegeneration and other cancers."

Recruitment for the trial continues to progress as expected, with recruitment for Part A now completed. 4D expects to announce data for all 12 Part A subjects in Q2 and to commence enrolment for Part B, which will expand the study based on the Part A data. It is expected that the study will be expanded to additional international trial locations and sites, initially in the US. 4D pharma also expects to discuss the findings from Part A and avenues for accelerated development with the regulatory agencies.