The AIM-listed firm said MRx0518 is in an ongoing Phase I/II clinical trial in combination with immune checkpoint inhibitor (ICI) Keytruda (pembrolizumab), in patients with advanced malignancies who have previously progressed on ICI therapy.
The study is comprised of two parts – Part A, an initial safety phase assessing dose-limiting toxicities of the combination which was completed in May last year, and the Part B cohort expansion phase to assess clinical benefit in addition to safety which has begun.
4D said 24 additional patients across five active US sites have now been treated in Part B of the ongoing study, adding that a safety review following the first Part B cohort of 10 renal cell carcinoma (RCC) patients has been completed indicating no dose-limiting toxicities.
The firm also said 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 and that recruitment will continue up to a total of 30 patients in each of these indications.
Meanwhile, the company said target tumour reductions in Part B patients have been observed as patients reach the first scheduled restaging timepoint of nine weeks. These included the first signals of anti-tumour activity for the combination in bladder cancer, adding to the previously reported activity in RCC and NSCLC in patients in Part A.
4D continued, saying that three Part A patients with RCC and NSCLC that were previously reported to have experienced clinical benefit continue on the study, with two of these patients having now been treated for over 18 months and have seen further target tumour reductions or extended disease control.
Following the positive results in RCC and NSCLC in Part A, the new tumour cohorts added to Part B of the study are now open to recruitment, with 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, now eligible for inclusion. Enrolment for the trial is expected to complete in the fourth quarter of 2021.
Meanwhile, 4D said five patients are now enrolled in a Phase I trial to evaluate the safety and efficacy in 15 patients of using MRx0518 and hypofractionated radiation treatment prior to surgery for pancreatic cancer.
The company said the study will generate “valuable data to assess the relationship between systemic and tumour biomarkers, as well as clinical outcomes”, adding that study treatment is well tolerated to date. 4D said enrolment is continuing and it expects to receive initial data from the trial in 2021.
Finally, the firm said 17 patients in a completed Part A of a Phase I study of MRx0518 in Neoadjuvant Setting Monotherapy are continuing in the follow-up phase for survival outcomes.
4D said biomarker and safety data from the study was presented at the Society for Immunotherapy of Cancer (SITC) Annual Meeting 2020 and demonstrated “systemic immune and tumour microenvironment modulation” following two to four weeks of treatment with MRx0518. It added that additional biomarker analyses are underway to further investigate the immune response induced by MRx0518 which it said may inform an optimisation of Part B of the study.
“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 [coronavirus]”, 4D Pharma’s chief scientific officer Alex Stevenson said in a statement.
“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 tumour 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”, the CSO added.
Shares in the company rose 4.6% to 120.8p in early trading on Wednesday.