Pembrolizumab and MRx0518 Shows Clinical Benefit in Patients With RCC

The clinical benefit of pembrolizumab (Keytruda) and MRx0518 has been demonstrated in patients with renal cell carcinoma that have progressed on a prior immune checkpoint inhibitor (ICI), meeting the primary efficacy end point in part B of a study examining the combination in patients with solid tumors that have progressed on a prior immune checkpoint inhibitor (ICI), according to an announcement by 4D pharma plc.¹

Data come from the ongoing study (NCT03637803) of MRx0518 in combination with the anti-PD-1 therapy, pembrolizumab, being conducted to examine the combinations safety and efficacy in patients with solid tumors who have previously experienced clinical benefit on prior ICI therapy and subsequently developed progressive disease.²

"Today’s results in renal cell carcinoma, meeting the predefined primary efficacy endpoint early in this difficult to treat population, marks another important step forward for MRx0518 and the increasing importance of the microbiome in cancer treatment," said Alex Stevenson, MD, chief scientific officer, 4D pharma plc, in the press release. "Meeting the primary efficacy endpoint for this group is crucial for the future development of MRx0518, and these data are highly informative for our strategy going forward as we determine next steps in RCC."

The phase 1/2, open label study aims to enroll around 132 participants who will be treated with pembrolizumab intravenously every 3 weeks in addition to 1 capsule twice a day of MRx0518 starting on the day of first pembrolizumab dose. Treatment will continue as long as clinically relevant, until disease progression, unacceptable AEs or withdrawal of consent up to a maximum of 35 cycles.

Enrollment in the study is open to patients aged 18 and older with histological or cytological evidence of advanced or metastatic or recurrent non-small cell lung cancer, RCC, bladder cancer or melanoma. Other requirements include that they must have at least one measurable lesion per RECIST v 1.1 criteria, failure to respond or intolerance to standard therapy or for whom no appropriate therapies are known to provide clinical benefit, has previously received at least 2 doses of a PD-1/PD-L1 inhibitor, has demonstrated disease progression after PD-1/ PD-L1 therapy, and has adequate organ function.

Primary end points of the trial include assessing the safety and tolerability of the combination of MRx0518 and pembrolizumab through the collection of adverse events and assessing the combination's clinical benefit. The key secondary end points are antitumor effect with other outcomes including biomarkers of treatment effect in blood and tumors, microbiota and metabolome, and overall survival.

Part B of the study currently has enrolled 20 patients with RCC. Out of the first 16 evaluable patients, 4 have achieved clinical benefit and at least 6 months of stable disease. MRx0518 continues to be safe and well tolerated.

4D pharma plc plans on discussing next steps regarding the development path of MRx0518 and a potentially pivotal study in patients with ICI-refractory RCC, and the study will continue to recruit patients in the RCC and 3 tumor groups, with potential expansion into other types of ICI resistance, according to the press release.

REFERENCES:

4D pharma announces positive interim results from the phase I/II study of the combination of MRx0518 and KEYTRUDA (pembrolizumab) for the treatment of renal cell carcinoma. News release. Business Wire; March 23, 2022. Accessed March 24, 2022. https://bit.ly/3DoA0Xl

Live Biotherapeutic Product MRx0518 and Pembrolizumab Combination Study in Solid Tumors. Clinicaltrials.gov. Accessed March 24, 2022. https://clinicaltrials.gov/ct2/show/NCT03637803?term=MRx0518&draw=2&rank=3