Investigational Anti-Clever-1 Antibody Shows Early Activity in Advanced Solid Tumors

Bexmarilimab, a novel anti-Clever-1 antibody, has shown signals of significant efficacy as a treatment of patients with 10 hard-to-treat solid tumors, according to an update from the phase 1/2 MATINS clinical trial (NCT03733990) announced in a press release by Faron Pharmaceuticals Oy.

“This is very exciting data supporting bexmarilimab's unique mechanism of action and adding to the accumulating evidence of bexmarilimab's broad potential across a range of hard-to-treat cancers. The early observations of survival benefit and the stark contrast in the progression of disease among patients who do not respond to bexmarilimab therapy show the clinical significance of Clever-1 as immunotherapy target and the potential patient benefit when its immune-suppressive control is removed,” said Markku Jalkanen, chief executive officer, Faron Pharmaceuticals Oy, in a statement.

Following 4 cycles of treatment with bexmarilimab, a survival benefit was observed in 10 patients who had a response to the agent. In comparison to patients who did not respond to bexmarilimab (n = 57), the overall risk of death was reduced by 88% (HR, 0.119; CI, 0.016-0.863) in responders. Contrarily, in the non-responders, development of progressive death continued and 85% died within the first 100 days.

Only 1 of the patients who responded to treatment with bexmarilimab died during the same time period with the median overall survival not yet reached. Bexmarilimab also led to an extended progression-free survival in the responders with a 93% reduction in the risk of disease progression compared with the non-responder group (HR, 0.068; CI, 0.016-0.290).

In a previous announcement, it was revealed that a signal of clinical activity was observed in only 5 of the 10 disease cohorts included in the study. Specifically, early benefit was seen in patients with colorectal cancer, cutaneous melanoma, ovarian cancer, hepatocellular cancer, and cholangiocarcinoma. Now, bexmarilimab is also achieving clinical activity in the gastric and uveal melanoma cohorts. The investigation is ongoing to determine whether patients with estrogen receptor–positive (ER+) breast cancer, pancreatic cancer, and anaplastic thyroid carcinoma derive benefit from the agent.

Previously, it was announced that patient recruitment in the MATINS trial was showing strong growth for part 2 of the study, which is the first dose-expansion phase. The target enrollment for the study is 650 patients. The lowest dose of bexmarilimab administered in the study is 0.1 mg/kg given in 3-week intervals. Dosing of bexmarilimab can escalate to as high as 10 mg/kg until the optimal dose of the agent is found.

MATINS is a first-in-human, open-label, 3-part, dose-finding, and separate cohort expansion study. The goal of the study is to determine the safety, tolerability, and preliminary efficacy of bexmarilimab in advanced solid tumors. The cancers of focus in the study include advanced melanoma, uveal melanoma, cholangiocarcinoma, gallbladder cancer, ER+ breast, gastric, ovarian, pancreatic, colorectal, liver, and anaplastic thyroid cancer in patients who have exhausted all other options of therapy and are at risk of dying from their disease.

The primary end points assessed in the study include dose-limiting toxicities, the incidence of treatment-emergent adverse events, CLEVER-1 positivity in the tumor, and objective response rate.

Patients with advanced and hard-to-treat solid tumor are eligible to enroll in MATINS given they are 18 years of age or older with a tumor sample; have 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. Those with recent cancer treatment, serious infection, brain metastases, a history of second malignancy, HIV, cytomegalovirus infection, active autoimmune disorder, prior organ transplant, or patients on dialysis or who are pregnant or breastfeeding were excluded from the study. Additional exclusion criteria for patients with hepatobiliary cancers included any prior ablative therapy, hepatic encephalopathy, ascites, and Child-Pugh score of 7 or higher.

“We look forward to gathering further data from these patient cohorts to support the design of our pivotal trials for bexmarilimab,” said Jalkanen, in the press release.

Based on the data observed, the data monitoring committee (DMC) recommended that more frequent dosing schedules be investigated in the 6 cohorts that displayed early clinical benefit. In addition, the DMC recommended evaluating higher doses of the drug.

_Reference:

_{Bexmarilimab (Clevegen) development update. News release. Faron Pharmaceuticals Oy. March 22, 2021. Accessed March 22, 2021.}