None listed
Conditions
Sponsors
Faron Pharmaceuticals Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent. 2. Projected life expectancy of at least 12 weeks. 3. Male or female patients = 18 years of age who present with one of the following conditions: a. Morphologically confirmed diagnosis of MDS based on 2016 WHO classification with indication for azacitidine treatment based on local standard medical practice with one of the following risk categories based on the rIPSS: i. Very high (> 6 points) ii. High (> 4.5 - = 6 points) iii. Intermediate (> 3 - = 4.5 points). b. Morphologically confirmed diagnosis of CMML based on 2016 WHO classification with 10-19 % marrow blasts with indication for azacitidine treatment based on local standard medical practice. c. CMML and MDS patients who presents with failure to achieve response to therapy with HMA or therapy regimen including HMA. Failure is considered if the patient has not achieved CR or mCR response after 4 cycles of therapy or the disease is progressing (increasing bone marrow blast count with decreasing blood counts) during treatment with HMA. d. Morphologically confirmed diagnosis of relapsed or refractory AML (except acute promyelocytic leukemia) following at least 1 line of prior therapy with indication for azacitidine treatment based on local standard medical practice. e. Morphologically confirmed diagnosis of AML in patients unfit for induction therapy with indication for azacitidine-venetoclax treatment based on local standard medical practice. Specific criteria for non-eligibility for induction chemotherapy: ? Patient must be = 75 years of age OR ? = 18 to 74 years of age and ineligible for intensive chemotherapy meeting at least one of the criteria following: • Clinically significant comorbidities, as documented by at least 1 of the following: o Left ventricular ejection fraction (LVEF) = 50%. o Lung diffusion capacity for carbon monoxide (DLCO) = 65% of expected. o Forced expiratory volume in 1 second (FEV1) = 65% of expected. o Chronic stable angina or congestive heart failure controlled with medication. o Eastern Cooperative Oncology Group (ECOG) performance status 2 or 3. ? Other contraindication(s) to anthracycline therapy (must be documented); creatinine clearance =30 mL/min to 1.5 to = 3.0 × upper limit of normal (ULN). ? Adverse risk genetics and/or TP53 mutation associated with poor outcome with standard chemotherapy. ? Antecedent MDS treated previously with standard chemotherapy and/or allogeneic transplantation. 4. Leukocyte count =65 years) yes F.1.3.1 Number of subjects for this age range 172
Exclusion criteria
Exclusion criteria: 1. Patient has acute promyelocytic leukemia (APL). 2. Myeloproliferative CMML as defined by leukocyte count > 13 x109/L. Of note, the use hydroxycarbamide is not allowed to meet this criterion in patients with CMML. 3. ECOG >2 (except newly diagnosed AML where ECOG 3 is allowed for patients = 18 to 74 years). 4. Patient has known active central nervous system (CNS) involvement with myeloid malignancy (note: CSF or radiological investigations are not required without clinical suspicion). Patients with prior history of CNS involvement may be eligible if they had 2 consecutive lumbar punctures negative for CNS leukemia prior to enrollment and no clinical signs of active or progressive CNS leukemia. 5. Patient with human immunodeficiency virus (HIV) infection or active hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. 6. Patient has cardiovascular disability status of New York Heart Association Class >2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in palpitations, fatigue, dyspnea, or anginal pain. 7. Patient has a chronic respiratory disease that requires continuous oxygen use; evidence of other clinically significant condition(s) that in the opinion of the investigator would adversely affect his/her participation in this study; active or poorly controlled systemic infection requiring therapy (viral, bacterial, or fungal); or graft versus host disease requiring treatment with immunosuppressants or steroids = 10mg prednisolone or equivalent. 8. Allogeneic transplantation less than 6 months prior screening. 9. Patient has a history of other malignancies prior to study entry, with the exception of previous malignancy confined and surgically resected (or treated with other modalities) with curative intent and have not recurred within 2 years after the last therapy prior to study treatment. Of note, patients on maintenance therapy such as tamoxifen for breast cancer or other maintenance approaches would be eligible as long as the malignancy did not recur within 2 years prior to study treatment. 10. Patient with active auto-immune disorder (except type I diabetes, celiac disease, hypothyroidism requiring only hormone replacement, vitiligo, psoriasis, or alopecia). 11. The patient requires systemic corticosteroid (=10 mg/day prednisone or equivalent) or other immunosuppressive treatment. Topical, nasal, inhaled and ophthalmic steroids are allowed. 12. Use of live (attenuated) vaccines for 30 days prior to the start of study treatment, during treatment, and until last visit. 13. 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 administration. 14. Major surgery within 4 weeks of the first dose of study treatment (procedures like insertion of a central venous access device are not considered as major surgery). 15. Any immunotherapy or investigational therapy within preceding 4 weeks from the first study treatment administration and during the study. 16. Pregnant or lactating women. 17. Women of child-bearing potential (WOCBP), unless they are using highly effective methods of contraception *) for at least 1 month prior to first dose of study treatment and agreement to use such a method during study participation and for an additional 12 weeks after stopping
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I 1.To determine the safety and tolerability of bexmarilimab in combination with SoC treatment to identify the recommended dose for expansion (RDE). Phase II 1.To evaluate the preliminary clinical efficacy of bexmarilimab at recommended phase 2 dose (RP2D) in combination with SoC.;Secondary Objective: Phase I 1.To assess preliminary clinical efficacy of bexmarilimab in combination with SoC treatment. 2.To characterize the pharmacokinetic (PK) profile of bexmarilimab in combination with SoC treatment. 3.To assess the immunogenicity of bexmarilimab. Phase II 1.To further evaluate the extended safety and tolerability of bexmarilimab at RDE/one dose level below the RDE/RP2D in combination with SoC treatment. 2.To investigate additional preliminary efficacy parameters of bexmarilimab in combination with SoC. 3. To characterize the pharmacokinetic (PK) profile of bexmarilimab in combination with SoC treatment. 4.To assess the immunogenicity of bexmarilimab. ;Primary end point(s): Phase I 1.Reporting of incidence and frequency of dose limiting toxicities (DLTs), and frequency and severity of adverse events (AE), SAEs and laboratory abnormalities. Phase II 1.Preliminary efficacy will be investigated per indication as follows: oComplete response (CR) rate for MDS and CMML-2. oOverall response rate (ORR) for MDS and CMML failure to prior HMA. oCR for r/r AML. oCR rate for newly diagnosed AML. ;Timepoint(s) of evaluation of this end point: -During the whole DLT period (28 days) for safety parameters -AEs during the whole study -Response assessments for preliminary efficacy done end of cycle 1 to cycle 6, followed by every 3 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I 1. Clinical efficacy measures include disease-specific response criteria and progression and survival analyses. 2. PK samples at defined timepoints of single and repeat bexmarilimab administration and derived PK parameters. 3. Anti-bexmarilimab antibody detection. Phase II 1. Frequency and severity based on NCI-CTCAE v 5.0 grading of adverse events (AE), SAE and laboratory abnormalities. 2. Extended preliminary efficacy to include disease-specific response criteria and progression and survival analyses. 3. Anti-bexmarilimab antibody (immunogenicity) detection. ;Timepoint(s) of evaluation of this end point: -PK done throughout the study in Phase I and Phase II pre-dose and post-dose timepoints. -Progression and survival to be followed up to 24 months after first study drug dose (every 3 months) -ADA: aligned with PK sampling throughout the study. -AEs during the whole study -Response assessments for preliminary efficacy done at the end of cycle 1 to cycle 6, followed by every 3 months. | — |
Countries
Finland, United States
Contacts
Public ContactRegulatory Affairs
Faron Pharmaceuticals Ltd.
Outcome results
None listed