Results from the melanoma cohort the MATINS trial will be shared at the 18th Congress of the European Association of Dermato-Oncology.
Compelling results from the melanoma cohort in the ongoing phase 1/2 MATINS (Macrophage Antibody to Inhibit Immune Suppression, NCT03733990) trial will be presented at the 18th Congress of the European Association of Dermato-Oncology (EADO) to be held in Seville, Spain, April 21 to April 23, 2022. This announcement comes from a press release by thecoordinators of the trial, Faron Pharmaceuticals Ltd.1
The MATINS study is researching bexmarilimab (Clevegen) as a monotherapy treatment. The melanoma cohort within the study is 1 of the 10 advanced treatment-resistant solid tumor types included in part 2 of the study, which consists of 110 patients. Data from 11 melanoma patients, including the cohort of 10 patients in part 2 and 1additional patient with same dosing regimen from part 1, who were refractory to checkpoint inhibition are being presented at the congress.
Of the 11 patients, 4 experienced clinical benefit with 1 patient experiencing a partial response after 2 cycles of bexmarilimab. This patient displayed a reduced tumor growth by 40% from baseline but was discontinued before a confirmatory scan was performed. In part 2, 3 patients had stable disease with a clinical benefit rate (CBR) of 30%.
Patients who experienced clinical benefit following treatment in part 2 were estimated to have a 12-month survival of 100% vs a 12-month survival of 33.3% for patients who showed no CBR.
All patients were treated with 1mg/kg of bexmarilimab monotherapy every 3 weeks. The median number of previous treatment lines was 3, and the median age of patients was 60.
Bexmarilimab targets tumor associated macrophages, which are known to be immunosuppressive, make up nearly 50% of the tumor mass, and limit the efficacy of currently approved cancer immunotherapies, including anti PD-1/L1. Melanoma is among 5 different tumor types from the original 10 studied to have shown the strongest CBR of 30%. CBR is defined as partial response or stable disease. After treatment with bexmarilimab, the strong CBR of other tumor types were found ingastric cancer (30%), cholangiocarcinoma (30%), hepatocellular carcinoma (40%) and breast cancer (40%).
A preliminary biomarker analysis, including the melanoma cohort, showed that patients were more likely to experience clinical benefit following treatment with bexmarilimab if they had higher intra-tumoral Clever-1 positivity, low baseline levels of serum interferon gamma (IFNy), and tumor necrosis factor alpha. A rise in serum IFNy levels was seen during treatment among patients who experienced clinical benefit. IFNy is a necessary pro-inflammatory cytokine for response to checkpoint inhibitors like PD-1/L1, highlighting bexmarilimab's combination potential.
"This rate of clinical benefit is particularly striking when you consider these are heavily pre-treated patients, all of whom were refractory to currently approved checkpoint inhibitor therapy," said Marie-Louise Fjällskog, MD, PhD, chief medical officer of Faron. "Bexmarilimab's ability to ignite an immune response in these patients means that it may serve as a catalyst for the immune system allowing initially checkpoint inhibitor resistant patients to become responsive to PD-1/L1 blockade."
"Additionally, the biomarker analysis among melanoma patients is consistent with our broader analyses and suggests that two cytokines, which can be measured by a standard blood test as part of a patient's routine care, could hold the key to understanding which patients will gain the greatest benefit from this novel immunotherapy. Knowing which patients are most likely to respond to treatment is key to both the development process and the successful roll out of new therapeutic approaches."