Phase I/II Open-Label Study to Assess Safety, Tolerability and Preliminary Efficacy of the CLEVER-1 Antibody Bexmarilimab in Combination With Azacitidine or Azacitidine/Venetoclax in Patients With Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia or Acute Myeloid Leukemia BEXMAB

What's the purpose of this trial?

This is a study to assess the safety of increasing dose levels of bexmarilimab when combined with standard of care (SoC) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML); Phase 1 aims to identify the recommended phase 2 dose (RP2D) of bexmarilimab based on safety, tolerability and pharmacological activity; Phase 2 will investigate the preliminary efficacy of the combination treatment in selected indications from Phase 1.

This trial is currently open and accepting patients.

What will happen during the trial?

You may be able to join this trial if you:

The following criteria is a partial list of reasons why patients may be eligible to participate in this clinical trial. Further evaluation with a medical professional is required.

Inclusion Criteria:

* Patient ≥ 18 years of age who presents with one of the following conditions:

* Morphologically confirmed diagnosis of MDS with revised International Prognostic Scoring System (rIPSS) risk categories: intermediate, high and very high.
* Morphologically confirmed diagnosis of CMML-2 with indication for azacitidine treatment.
* CMML and MDS patient with response failure to HMA or therapy regimen including HMA.
* Morphologically confirmed diagnosis of r/r AML following at least 1 line of prior therapies with indication for azacitidine treatment.
* Morphologically confirmed diagnosis of AML in patients unfit for induction therapy with indication for azacitidine-venetoclax treatment.
* Leukocyte count \< 20 x10\^9/L (\< 25 x10\^9/L for newly diagnosed AML). Hydroxycarbamide use is permitted to meet this criterion in MDS and AML but not in CMML.
* Adequate renal function.
* Adequate liver function.

Exclusion Criteria:

* Patient with acute promyelocytic leukemia (APL) or myeloproliferative CMML as defined by leukocyte count \> 13 x10\^9/L.
* Eastern Cooperative Oncology Group (ECOG) performance status \>2 (except newly diagnosed AML where ECOG 3 is allowed for patients \< 75 years).
* Allogeneic transplantation less than 6 months prior screening.
* Patient with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia).
* The patient requires systemic corticosteroid (≥10 mg/day prednisone or equivalent) or other immunosuppressive treatment.
* Less than 21 days since the last dose of intravenous anticancer chemotherapy or less than 14 days or five half-lives (whichever is shorter) from a small molecule targeted therapy or oral anticancer chemotherapy before the first study treatment.
* Any immunotherapy or investigational therapy within preceding 28 days from the first study treatment.
* Pregnant or lactating women.
* History of chronic ulcers or clinically relevant liver disease leading to Child Pugh Score C or higher.

Additional Trial Information

Phase 1/2

Enrollment: 181 patients (estimated)

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Published Results

Encouraging Efficacy Observed in Bexmab Study: A Phase 1/2 Study to Assess Safety and Efficacy of Bexmarilimab in Combination with Standard of Care in Myeloid Malignancies

November 28, 2023

As of 25 July 2023, 22 patients have been enrolled in the doublet (MDS n=5; MDS HMA failed n=5; r/r AML n=12). Baseline characteristics are shown in Table 1. 8/10 MDS/MDS HMA-failed patients were of high to very high risk based on rIPSS; of the r/r AML 7/12 patients had adverse risk based on ELN 2017. The median number of prior therapies for the MDS HMA-failed patients was 1 (range 1-2). The median number of prior therapies for the r/r AML patients was 2 (range 1-4) with all patients having failed prior HMA-containing therapies and 7/12 having received prior HMA plus venetoclax.

The majority of observed adverse events (AE) were Grade 1-2 and no dose limiting toxicities have been reported. As of 25 July 2023, a total of 10 BEX related AEs have been reported (8% of all treatment emergent AEs) with four of these events of ≥ Grade 3, two being immune related (capillary leak syndrome and hemophagocytic lymphohistiocytosis).

Sustained target engagement of soluble Clever-1 of up to 75% compared to baseline was seen at all tested dose levels in patient blood. Activity of BEX in patient BM was demonstrated using receptor binding assays with BEX treatment resulting in decreased blast Clever-1 expression at all dose levels of the doublet cohort. Increased immune activation as measured using HLA expression and T/NK cell numbers in patient BM was observed after BEX treatment across indications. Up to 2-3-fold increase of CD8 T and NK cells in the BM of BEX treated patients was observed.

Preliminary efficacy shows objective responses in 8/15 evaluable patients across all tested BEX doses. Four were observed in patients with prior HMA-failure and four patients stayed on treatment > 6 months. Clinical activity for frontline MDS was seen as one complete remission (CR), marrow CR (mCR) and hematologic improvement for platelets (HI-P); for MDS with HMA failure as one CR, mCR and partial remission (PR); for r/r AML as two incomplete CRs (CRi). Based on accumulating data, responses are observed between end Cycle 1 and end Cycle 4 for all BEX doses.

Conclusion

Combining BEX plus azacitidine is well-tolerated and shows efficacy across indications. Additional clinical and pharmacodynamic data of the completed Ph1 of the study will be presented during the meeting. Ph2 of BEX plus azacitidine will open in the 2 nd half of 2023 in HMA-failed r/r AML and/or higher risk MDS patients.

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Trial Links

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Trial Locations

All Trial Locations

View all clinical trial locations sorted by state.

California

City of Hope Comprehensive Cancer Center Beckman Research Institute

Duarte, CA

Open and Accepting

Connecticut

Yale Cancer Center Smilow Cancer Hospital at Yale-New Haven

New Haven, CT

Open and Accepting

North Carolina

UNC Lineberger Comprehensive Cancer Center University of North Carolina

Chapel Hill, NC

Not Yet Accepting

Texas

MD Anderson Cancer Center The University of Texas

Houston, TX

Open and Accepting
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