Patients with higher risk myelodysplastic syndrome (MDS) who have not yet been treated for their disease MedDRA version: 21.1 Level: PT Classification code 10028533 Term: Myelodysplastic syndrome System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: ALX148
Product Code: ALX148
Pharmaceutical Form: Solution for injection
INN or Proposed INN: NA
CAS Number: 2484949-51-9
Current Sponsor code: ALX148
Other descriptive name: ALX148
Conce
Sponsors
ALX Oncology Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult patients with documented diagnosis of higher risk MDS (IPSS-R score >3.5) who have had no prior exposure to hypomethylating agents or cytotoxic chemotherapy (prior use of single agent lenalidomide for low or intermediate-1 risk MDS with deletion 5q abnormality is allowed) for the treatment of MDS, and are considered appropriate candidates for single-agent AZA. 2. Bone marrow with >5% to =65 years) yes F.1.3.1 Number of subjects for this age range 78
Exclusion criteria
Exclusion criteria: 1. Patients with a history of autoimmune hemolytic anemia, autoimmune thrombocytopenia, or hemolytic transfusion reaction secondary to an acquired allo-antibody. 2. Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) for MDS or AML. If allo-HSCT was performed for another disease, patient must be at least a year post-HSCT, off all treatment for graft-versus-host disease (GVHD), and without any active GVHD. 3. Prior treatment with any anti-CD47 or anti-SIRPa agent. 4. Prior treatment with any hypomethylating agents or cytotoxic chemotherapy for MDS (except hydroxyurea up to day -1 of study and lenalidomide for low or intermediate-1 risk MDS with deletion 5q abnormality). 5. Patients with MPN/MDS overlap syndromes, including CMML. 6. Prior treatment with myeloid growth factors and erythropoiesis stimulating agents (ESAs) must be discontinued a minimum of 4-5 half-lives prior to initiation of study treatment. 7. Patients with intolerance to or who have had a severe allergic or anaphylactic reaction to antibodies or infused therapeutic proteins or patients who have had a severe allergic or anaphylactic reaction to any of the substances included in the study drug (including excipients). 8. Any experimental antibodies or live vaccines in the last 28 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. 9. Known active viral infections, including hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) related illness, or known active infection with SARS-CoV-2 (testing to be performed per local criteria). 10. Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, NYHA Class II or greater congestive heart failure, uncontrolled hypertension, cerebrovascular accident, transient ischemic attack, deep venous thrombosis (except for thrombi considered device-associated and not clinically significant), arterial thrombosis, symptomatic pulmonary embolism, or any other significant thromboembolism. Any major surgery, within 28 days prior to enrollment. 11. Current active treatment in another interventional therapeutic clinical study. 12. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate/breast/other cancer under control with hormone therapy alone, or other cancer from which the subject has been disease free for at least 2 years and felt to be at low risk for recurrence by the treating physician. 13. Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 14. Other severe acute or chronic medical or psychiatric condition, including uncontrolled systemic infection, recent (within the past year) or active suicidal ideation or behavior, or labora
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of ALX148 administered at the RP2D determined in Phase 1 in combination with AZA versus AZA alone on the investigator-assessed complete response rate (CRR) per IWG 2006 criteria in adult patients with previously-untreated higher risk MDS (IPSS-R score >3.5);Secondary Objective: • To assess the effect of ALX148 administered at the RP2D determined in Phase 1 in combination with AZA versus AZA alone on the complete response rate (CRR) per IWG 2006 criteria as determined by independent central review in adult patients with previously-untreated higher risk MDS (IPSS-R score >3.5) • To assess secondary measures of efficacy for ALX148 administered in combination with AZA versus AZA alone • To assess the safety and tolerability of ALX148 administered in combination with AZA versus AZA alone • To assess if ALX148 in combination with AZA improves global health status/quality of life (GHS/QoL) versus AZA alone based on patient reported outcome (PRO) assessment;Primary end point(s): The primary endpoint of the Phase 2 part of the study is complete response rate (CRR), assessed by investigator using IWG 2006 response criteria for MDS, defined as a best response of CR, with the final analysis to be performed after the last patient has completed 6 cycles of treatment or is considered evaluable for response.;Timepoint(s) of evaluation of this end point: In Phase 2, the final analysis to be performed after the last patient has completed 6 cycles of treatment or is considered evaluable for response. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence of marrow CR, objective response rate (ORR), hematologic improvement (HI) in erythrocytes (E), platelets (P), and neutrophils (N), red blood cell (RBC) and platelet (PLT) transfusion independence, frequency and level of measurable residual disease (MRD) • Duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), time to progression (TTP). • Percentage of patients able to proceed to allogeneic hematopoietic stem cell transplant (allo-HSCT). • Changes in global health status/quality of life (GHS/QoL) status based on patient reported outcome (PRO) assessment (Phase 2 only). • Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v. 5.0), timing, seriousness, and relationship to study therapy; • Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v. 5.0) and timing; • Pharmacokinetic parameters of ALX148 such as Cmax, Tmax, AUC, CL, and t1/2 as data permit; • Immunogenicity; Human serum ADA (anti-ALX148 antibody) samples will be analyzed for the presence or absence of anti-ALX148 antibodies.;Timepoint(s) of evaluation of this end point: Duration of response (DOR) is measured from the time measurement criteria are first met for CR, PR, mCR, CyR, or HI, until the first date that progressive disease (PD) is documented. Duration of CR is also measured from the time measurement criteria are first met for CR only, until the first date that progressive disease (PD) is documented. Patients who do not have any documentation of progression will be censored at their last tumor assessment. DOR will be evaluated in the responders population. Time to progression (TTP) is measured from start of treatment until progressive disease (PD) is documented. Patients who do not have any documentation of progression will be censored at their last tumor assessme | — |
Countries
Belgium, France, Germany, Italy, Korea, Republic of, Spain, United Kingdom, United States
Contacts
Public ContactChief Medical Officer
ALX Oncology Inc.
Outcome results
None listed