Bexmarilimab Plus SOC Continues to Show Early Activity in R/R AML and MDS

Bexmarilimab (FP-1305) in combination with standard-of-care (SOC) azacitidine or azacitidine plus venetoclax (Venclexta) demonstrated early signs of efficacy in patients with relapsed or refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), according to updated data from the ongoing phase 1/2 BEXMAB study (NCT05428969).¹

Findings indicated that of 5 patients who received bexmarilimab at 6 mg/kg plus azacitidine, 3 achieved an objective response (OR) of complete remission (CR) of blasts in the bone marrow (mCR). Of these 3 patients, 1 also experienced complete blood count recovery.

Across the 3 doublet dosing cohorts of 1 mg/kg, 3 mg/kg, and 6 mg/kg, 8 of 15 ORs were reported. Notably, half of these 8 patients had standard treatment with hypomethylating (HMA) agents fail them. All patients with MDS and previous HMA failure (n = 3) achieved ORs across the dosing cohorts; 1 patient had a PR, 1 had a mCR, and 1 had a CR.

Moreover, in the triplet dosing cohort (n = 6), where patients received bexmarilimab at 1 mg/kg plus azacitidine and venetoclax, 4 patients achieved an OR.

“We are extremely encouraged by the continued efficacy signals of bexmarilimab, and the long duration of responses seen so far,” Mika Kontro, MD, PhD, associate professor at the Helsinki University Hospital Comprehensive Cancer Center and principal investigator of the BEXMAB trial, stated in a press release. “Our goal is to offer a unique hope for patients with no other treatment options in this late stage of AML and MDS.”

The BEXMAB trial enrolled patients with frontline MDS or chronic myelomonocytic leukemia (CMML), those with CMML or MDS who had a HMA fail, and those with relapsed or refractory AML to the doublet population.² The triplet population included those with newly diagnosed AML unfit for chemotherapy.

The primary objective of the study is safety and tolerability, as well as identifying the recommended phase 2 dose.

Previous data presented at the 2023 EHA Congress had a data cutoff date of April 11, 2023. At this time point, 18 patients had received treatment on the study; 13 were given the doublet and 5 were administered the triplet.

In 10 evaluable patients, the median age was 69 years (range, 52-81), and 60% were male. Regarding baseline ECOG performance status, 40% had a status of 0, 40% had a status of 1, and 20% had a status of 2. Regarding Revised International Prognostic Scoring System for MDS Risk, 10% had high-risk disease and 20% had very high–risk disease. Risk according to the European LeukemiaNet criteria for AML included favorable (10%), intermediate (40%), and adverse (20%). Forty percent of patients received 2 prior lines of therapy.

At the meeting, ORs were reported in 5 of 10 evaluable patients spanning indications, and a reduction of bone marrow blasts was noted in more than 50% of patients. Additionally, a dose proportional increase in bexmarilimab C_max, AUC_0-48h, and AUC_last was observed with the doublet regimen. Investigators also noted Clever-1 target engagement in the bone marrow of patients, and a boost in antigen presentation as well as T-cell activity.

Moreover, the addition of bexmarilimab to azacitidine was found to have acceptable tolerability, with no dose-limiting toxicities reported. No serious or grade 3 or higher adverse effects (AEs) associated with the study drug were observed. Notably, no bexmarilimab-associated AEs led to treatment discontinuation.

Treatment-related AEs (TRAEs) of any grade occurred in half of the 10 patients. The most common TRAEs were constipation (grade 1/2, 20%), nausea (10%), pyrexia (10%), and vomiting (10%).

Faron Pharmaceuticals, Ltd. shared plans to seek advice from the FDA in the third quarter of 2023.¹ In the second half of the calendar year, they anticipate moving forward with the phase 2 portion of BEXMAB in patients with AML who are refractory to SOC and in those with MDS who have experienced HMA failure.

References

1. Faron updates positive clinical data from phase I/II BEXMAB study of bexmarilimab in relapsed/refractory AML and MDS: BEXMAB study update. News release. Faron Pharmaceuticals, Ltd. July 19, 2023. Accessed July 19, 2023. https://www.faron.com/news-events/news-and-press-releases?rnsid=1703177&cid=2223
2. Kontro M, Siitonen T, Rimipilainen J, et al. A phase I/II study to assess safety, tolerability and preliminary efficacy of bexmarilimab in combination with standard of care in patients with myeloid malignancies (BEXMAB). Presented at: 2023 EHA Congress; June 8-11, 2023; Frankfurt, Germany. Abstract P542.