Bexmarilimab Plus SOC Continues to Elicit Responses in R/R AML and HMA-Refractory MDS

The addition of bexmarilimab (FP-1305) to standard-of-care (SOC) azacitidine or azacitidine plus venetoclax (Venclexta) continued to elicit responses in patients with relapsed or refractory acute myeloid leukemia (AML) and those with myelodysplastic syndrome (MDS) who were refractory to hypomethylating agents (HMAs), according to updated data from the phase 1/2 BEXMAB study (NCT05428969).¹

The updated findings include information on a total of 22 patients who completed 2 or more cycles of treatment; of these patients, 12 had AML, 5 had treatment-naïve MDS, and 5 had HMA-refractory MDS. Notably, 8 of 11 patients achieved complete remission (CR) in the bone marrow with or without blood count recovery.

Notably, the objective response rate (ORR) was highest in the subset of patients with HMA-refractory MDS, at 80%. In the total population given the doublet (n = 22), the ORR was 50%, with the majority of patients (75%) experiencing blast reduction.

At all dose levels evaluated, bexmarilimab continues to have acceptable tolerability with no dose-limiting toxicities reported. To date, 18 treatment-related adverse effects have been reported with most being low grade; 5 cases were noted to be grade 3 or higher and included immune-related toxicities like capillary leak syndrome, hemophagocytic lymphohistiocytosis, and cryptogenic pneumonia. One case of increased liver enzymes was also observed.

“The emerging data from phase 1/2 continue to be extremely promising, showing continued good safety, encouraging efficacy, and long durations of response,” Markku Jalkanen, MD, MSc, PhD, chief executive officer of Faron Pharmaceuticals, Ltd. “These results strongly support the planned next step of beginning enrollment of the phase 2 part of the BEXMAB study.”

BEXMAB is enrolloing patients with morphologically confirmed MDS who had intermediate-, high-, or very high–risk disease by revised International Prognostic Scoring System criteria; chronic myelomonocytic leukemia (CMML)-2 who were slated to received azacitidine; CMML and MDS who did not respond to a HMA-containing regimen; relapsed or refractory AML with prior exposure to at least 1 therapy and who were indicated for azacitidine; AML that was not fit for induction treatment but was indicated for azacitidine and venetoclax.² Patients also need to be at least 18 years of age, have a leukocyte count that was under 20 x 109/L, and less than 25 x 109/L if they had newly diagnosed disease, as well as acceptable renal and liver function.

If patients have acute promyelocytic leukemia or myeloproliferative CMML or an ECOG performance status greater than 2, they will be excluded. Patients also cannot have undergone allogeneic transplantation less than 6 months before screening, nor could they have active autoimmune disorder. Other exclusion criteria include: requiring systemic corticosteroids; having received chemotherapy or small molecule therapy less than 21 days or 14 days, respectively, before study treatment was initiated; or having received immunotherapy or another investigative agent within 28 days before study treatment was started.

The phase 1 portion of the trial utilized a Bayesian Optimal Interval dose-escalation design that was comprised of 2 experimental arms: those with intermediate or high risk MDS, CMML with 10% to 19% bone marrow blasts, MDS or CMML that had progressed on an HMA, and relapsed/refractory AML; and those with newly diagnosed AML who were not candidates for induction therapy. Azacitidine was administered according to the label, bexmarilimab was evaluated at 4 dose levels given once weekly followed by once every 2 weeks.

The key objective of this portion of the study was to evaluate the safety, tolerability, and early efficacy of bexmarilimab in this population, including determining a safe and tolerable dose of the agent, and a maximum tolerated dose when the agent is paired with SOC.

Earlier data from this portion of the trial showed that of 5 patients who received bexmarilimab at 6 mg/kg plus azacitidine, 3 experienced an objective response (OR) of CR of blasts in the bone marrow (mCR); of these 3 patients, 1 also achieved complete blood count recovery.³

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 HMAs fail. All patients with MDS and HMA failure (n = 3) achieved ORs across the dosing cohorts; 1 patient experienced a partial response, 1 had a mCR, and 1 had a CR. Additionally, in the triplet dosing cohort (n = 6), where patients received bexmarilimab at 1 mg/kg plus azacitidine and venetoclax, 4 patients achieved an OR.

As of October 5, 2023, a total of 29 patients had been recruited to the doublet cohort.¹ The clinical-stage biopharmaceutical company shared plans to begin phase 2, the dose-expansion portion of the research, in the fourth quarter of 2023.

This will utilize a Simon’s 2-stage design for each indication selected to proceed from phase 1. The key objectives will be to further examine the safety and preliminary efficacy of bexmarilimab given at the recommended phase 2 dose in combination with SOC in patients with HMA-refractory MDS and relapsed/refractory AML.^1,2

This phase will begin with dose optimization and is anticipated to enroll between 28 and 32 participants who will be randomized between 2 selected doses.1 The number of clinical sites throughout the United States is expected to increase from 2 to 5 to boost recruitment.

Recently, in August 2023, the FDA granted an orphan drug designation to bexmarilimab for use as a potential therapeutic option in patients with AML.⁴

References

1. Faron announces positive BEXMAB study update. News release. Faron Pharmaceuticals, Ltd. October 11, 2023. Accessed October 11, 2023. https://otp.tools.investis.com/clients/uk/faron2/rns/regulatory-story.aspx?cid=2223&newsid=1724404
2. A study to assess safety, tolerability and preliminary efficacy of bexmarilimab in combination with standard of care in patients with hematological malignancies (BEXMAB). ClinicalTrials.gov. Updated June 23, 2023. Accessed October 11, 2023. https://clinicaltrials.gov/study/NCT05428969
3. 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 October 11, 2023. https://www.faron.com/news-events/news-and-press-releases?rnsid=1703177&cid=2223
4. Faron receives FDA orphan drug designation for bexmarilimab in acute myeloid leukemia. News release. Faron Pharmaceuticals. August 29, 2023. Accessed October 11, 2023. https://otp.tools.investis.com/clients/uk/faron2/rns/regulatory-story.aspx?cid=2223&newsid=1711777