4D Pharma Hits Efficacy Target in Renal Cell Carcinoma Trial

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4D pharma shared positive interim results from its Phase I/II study of a combination therapeutic for the treatment of renal cell carcinoma (RCC). The combination therapy utilizes its lead asset MRx0518 in combination with keytruda (pembrolizumab), a humanized antibody used in cancer immunotherapy treatments. 

The clinical trial began in August 2018, recruiting patients with solid tumors who have progressed on a prior immune checkpoint inhibitor (ICI), a type of drug that blocks checkpoint proteins made by immune system cells that “protect” malignant cells. Patients with non-small cell lung cancer, RCC, bladder cancer and melanoma who developed progressive disease even after being heavily treated were considered. 

Patients enrolled in the trial receive an IV infusion of pembrolizumab once every three weeks and take one capsule of MRx0518 twice daily after receiving their first infusion. The treatment period can last for up to 35 cycles or approximately two years. 

4D pharma announced Wednesday that in Part B of the study, which enrolled 20 patients with RCC, four of the first 16 evaluable patients have achieved clinical benefit when dosed with the combination therapy. The patients have achieved at least six months of stable disease, meeting the primary efficacy endpoint ahead of complete enrollment. MRx0518 was also safe and well-tolerated in those dosed. 

Alex Stevenson, chief scientific officer at 4d Pharma, told BioSpace that he is excited about the trial's results so far.

"The primary endpoint for Part B set by 4D pharma and our collaborators Merck & Co. (MSD) was for more than 3 patients out of a total of up to 30 patients per tumor type group to achieve clinical benefit," Stevenson said. "Out of the first 16 evaluable RCC patients, we have already hit 4 with clinical benefit, achieving the primary in this group."

MRx0518 is a live biotherapeutic product (LBP). LBPs are orally delivered single strains of bacteria that are derived from healthy human guts. Donor cells are grown at 4D pharma’s in-house cGMP-certified manufacturing facility where they are later encapsulated for administration and selective delivery to the gut. 

Live biotherapeutic products work by harvesting the power of the gut microbiome, an environment of trillions of micro-organisms and their gene products that colonize the human gastrointestinal tract. The gut microbiome plays a huge role in many diseases by influencing modulation of the human immune system, metabolism and neurological functioning by allowing bacteria to interact with different systems of the body.  

4D pharma has been working on a variety of LBPs for clinical development by utilizing its proprietary platform MicroRx. The platform can rapidly sift through a proprietary library of bacterial isolates for therapeutic functionality by identifying strains have significant effects in the human body and then targeting those diseases that are driven by pathways that match the host-response profile of the strain. 

Stevenson explained what the data in the trial means for patients. "The clinical data for MRx0518 to date suggests a favorable risk-reward profile – we are seeing meaningful benefit in advanced, heavily pre-treated patients not responding to other available therapies, without a notable increase in adverse events or serious adverse events," he said. 

Next up for 4D pharma is discussing future steps with partners and its Genitourinary Cancers Advisory Board for the development path of MRx0518. There are also plans to discuss a pivotal study in patients with ICI-refractory RCC. Patients will still be recruited in the ongoing combination therapeutic study in RCC and other oncological groups. 

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