Bexmarilimab Derives Overall Survival Benefit in PD-1 Blockade Refractory Melanoma

Results from the melanoma cohort of the phase 1/2 MATINS show the potential of bexmarilimab monotherapy and combined with other immunotherapies across solid tumors and hematologic malignancies.

Findings from the ongoing phase 1/2 MATINS trial revealed there to be a clinical benefit derived bexmarilimab (FP-1305) with 100% overall survival (OS) at 12-months in patients with PD-1 blockade refractory melanoma patients, according to Faron Pharmaceuticals Ltd.1

Patients who had cold tumors, defined by low baseline levels of pro-inflammatory cytokines, were more likely to have clinical benefit with bexmarilimab. For the patients who derived benefit from bexmarilimab, they had a seven-fold increase in serum interferon gamma (IFNγ). This suggests that retreatment with anti-PD-1 could be beneficial.

These results come from the 22 patients enrolled in the melanoma cohort of the trial which will be presented at the 19th International Congress of The Society for Melanoma Research taking place in Edinburgh, Scotland, October 17-20, 2022.

"Checkpoint inhibitors have transformed the treatment of metastatic melanoma, but far too many patients are not benefiting from currently approved immunotherapies," said Anna Minchom, MD, consultant medical oncologist at the Royal Marsden Hospital, team leader at the Institute of Cancer Research and investigator in the MATINS trial, in the press release. "The biomarker analysis in this trial of bexmarilimab is very interesting, indicating immune activation and pointing the way for combining bexmarilimab with other immunotherapies."

The first-in-human, open-label, 3-part, dose-finding MATINS study aims to identify the efficacy, safety, and tolerability of bexmarilimab in patients with advanced solid tumors, including advanced melanoma, uveal melanoma, cholangiocarcinoma, gallbladder cancer, estrogen receptor-positive breast cancer, gastric, ovarian, pancreatic, colorectal, liver, or anaplastic thyroid cancer.2

Patients are eligible to enroll in the trial if they are aged 18 years or older with advanced or hard-to-treat solid tumors for which they have exhausted all other options of therapy and are at risk of dying from their disease. One must have a tumor sample, a life expectancy of at least 12 weeks, histologically confirmed disease, an ECOG performance status of 0 or 1, measurable disease, and adequate bone marrow, liver, and kidney function to enroll in the trial.

The primary end points of the study include dose-limiting toxicities, the incidence of treatment-emergent adverse events, and objective response rate.

In the melanoma cohort of the trial, all patients had previously failed checkpoint inhibition and were treated with bexmarilimab alone at varying dose levels. The median age of patients in the melanoma cohort was 60 and the median number of previous treatment lines was 3.

Among the 22 patients, 5 (23%) experienced clinical benefit during therapy. Of the patients who completed 12-month follow-up completed, 100% (3/3) of patients who experienced clinical benefit were alive vs 11% (1/9) of patients who did not experience clinical benefit.

For patients who experienced clinical benefit, the median OS was 457 days vs 189 days for those who did not experience clinical benefit, representing a 2.4-fold increase in OS for patients with clinical benefit. Further, the mean baseline IFNγ levels for patients who experienced clinical benefit was ¼ of the mean value of patients who did not experience a clinical benefit.

These mean levels increased significantly and remained high over the course of treatment. This shows that the immune response was activated and the tumor was converted from cold to hot. Low levels of both IFNγ and TNFα were also observed, showing to be highly predictive of clinical benefit (area under the curve 0.87; 95% CI, 0.71-1.00) At baseline, higher intratumoral CLEVER-1 levels were also observed in the patients who experienced clinical benefit.

"These data, together with our biomarker analysis, reinforce bexmarilimab's unique proposition: Its capacity to ignite immunity in heavily pre-treated, last line cancer patients who either failed on or were ineligible for treatment with currently approved immunotherapy drugs," said Marie-Louise Fjällskog, MD, PhD, chief medical officer of Faron Pharmaceuticals Ltd, in the press release. "Our development program exploring the potential of bexmarilimab across solid tumors and hematologic malignancies, both as a monotherapy and in combination with standard of care therapies, seeks to further explore this novel immunotherapy's potential as a catalyst for the immune system."

References:
  1. Faron pharmaceuticals presents results from PD-1 blockade refractory melanoma cohort of MATINS trial at 19th international congress of the society for melanoma research. News release. Faron Pharmaceuticals Ltd. October 18, 2022. Accessed October 19, 2022. https://bit.ly/3D82er0
  2. A study to evaluate safety, tolerability and preliminary efficacy of FP-1305 in cancer patients (MATINS). ClinicalTrials.gov. Updated July 14, 2022. Accessed October 19, 2022. https://clinicaltrials.gov/ct2/show/NCT03733990