Relapsed or refractory multiple myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: EOS-448
Product Code: EOS884448
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: EOS884448
CAS Number: 2574438-65-4
Current Sponsor code: EOS884448
Other descriptive name:
Sponsors
iTeos Belgium SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria: Participants are eligible to be included in the study if all the following criteria are met: 1. Written informed consent signed in accordance with federal, local, and institutional guidelines, including consent for bone marrow aspirate (BMA) before and during administration of study treatment. 2. Age greater than or equal to (=) 18 years at the time of informed consent. 3. Documented diagnosis of MM. 4. Have received at least 3 prior lines of myeloma therapy including an IMiD, a proteasome inhibitor, and an anti-CD38 antibody in any order during the course of treatment for multiple myeloma (note: induction with or without bone marrow transplant and with or without maintenance therapy is considered one line) and not be candidate for regimens known to provide clinical benefit in this setting. 5. Must have progressed on their last line of myeloma therapy. 6. Measurable disease as defined by at least one of the following: a. Serum M-protein = 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for immunoglobulin A (IgA) myeloma, by quantitative IgA b. Urinary M-protein of at least 200 mg/24 hours by urine protein electrophoresis (UPEP) c. Serum free light chain (FLC) = 100 milligram per liter (mg/L), provided that FLC ratio is abnormal d. If SPEP is felt to be unreliable for routine M-protein measurement (example, for IgA or IgD MM), then quantitative immunoglobulin (Ig) levels by nephelometry or turbidometry are acceptable 7. Any non-hematological toxicities that patients had from prior treatments must have resolved to less than or equal (=) Grade 1 by C1D1 with the exception of alopecia. 8. Eastern Cooperative Oncology Group (ECOG) Performance Status of = 2. 9. Adequate hepatic function within 28 days prior to C1D1: Total bilirubin 45 mL per minute or greater using the formula of Cockroft and Gault (1976): a. CrCl (female) = (([140-age] x weight in kg)/(serum creatinine x 72)) x 0.85; b. CrCl (male) = ([140-age] x weight in kg)/(serum creatinine x 72) 11. Adequate hematopoietic function within 28 days prior to C1D1: total white blood cell count = 1,500/millimeter cube (mm^3), absolute neutrophil count (ANC) = 1,000/mm^3, hemoglobin = 8.0 g/dL. Platelet count = 75,000/mm^3 for Part 1. For Part 2: platelet count = 75,000/mm^3 for participants in whom < 50% of bone marrow nucleated cells are plasma cells, otherwise platelet count = 50,000/mm^3 12. Females of childbearing potential (FCBP) must: a. Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the participant practices true abstinence* from heterosexual contact. b. Either commit to true abstinence* from heterosexual contact or agree to use, and be able to comply with, 2 forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting study treatment, during the study treatment, and for at least 90 days after the last dose of study treatment. Contraception requirements are detailed in section 9.5 and the current version of th
Exclusion criteria
Exclusion criteria: Participants are excluded if any of the following criteria applies: 1. MM that does not express M-protein or FLC (i.e., non-secretory MM is excluded). 2. Documented active systemic amyloid light chain amyloidosis. 3. Active plasma cell leukemia. 4. Clinical evidence of central nervous system or pulmonary leukostasis, disseminated intravascular coagulation, or CNS MM. 5. Red Blood Cell transfusions and blood growth factors within 14 days of C1D1. 6. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy or plasmapheresis within 2 weeks prior to C1D1, and radio-immunotherapy within 6 weeks prior to C1D1. Patients on long-term glucocorticoids during Screening do not require a washout period. Prior radiation is permitted for treatment of fractures or to prevent fractures as well as for pain management. 7. Treatment with an investigational anti-cancer therapy within 4 weeks prior to C1D1, last infusion with CAR-T cell therapy within 12 weeks prior to C1D1. 8. Treatment with granulocyte colony-stimulating factor (G-CSF) within 4 weeks prior to C1D1. 9. History of Grade =2 pneumonitis, active autoimmune disease, or persistent immune-mediated toxicity caused by immune checkpoint inhibitor therapy of Grade =2 with the exception of residual endocrinopathy adequately substituted, vitiligo, Type 1 diabetes mellitus, or psoriasis not requiring systemic therapy. 10. Active neuropathy >Grade 2 (CTCAE v5.0). or Grade = 2 neuropathy with pain at Screening (within 28 days prior to C1D1). 11. History of life-threatening toxicity related to prior immune therapy or any toxicity that resulted in permanent discontinuation of prior immune therapy. 12. Prior autologous stem cell transplantation 470 milliseconds or any clinically significant abnormal electrocardiogram (ECG) finding at Screening. 16. Prior history of malignancies, other than MM, unless the subject has been free of the disease for = 5 years with the exception of the following noninvasive malignancies: a. Basal cell carcinoma of the skin b. Squamous cell carcinoma of the skin c. Carcinoma in situ of the cervix d. Carcinoma in situ of the breast e. Incidental histological findings of prostate cancer such as T1a or T1b using the Tumor/Node/Metastasis (TNM) classification of malignant tumors or prostate cancer that is curative 17. Uncontrolled active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose. 18. Known infection with human immunodeficiency virus (HIV). Testing is not required for eligibility. 19. Known active infection with hepatitis B (surface antigen); or infection with hepati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Dose escalation (Part 1): - To establish the safety and tolerability of EOS884448 (EOS-448) alone, and in combination with iberdomide with and without dexamethasone (DEX), in participants with relapsed/refractory multiple myeloma (RRMM) - To determine the recommended phase 2 dose (RP2D) of EOS-448 alone and the RP2D of the combination of EOS-448 with iberdomide with or without DEX in participants with RRMM. Expansion (Part 2): - Further evaluate the safety and tolerability of EOS-448 in the corresponding expansion cohorts either alone, or in combination with iberdomide with or without DEX, in participants with RRMM - Assess the clinical activity of EOS-448 in the corresponding expansion cohorts either alone or in combination with iberdomide with or without DEX in participants with R RMM;Secondary Objective: Dose escalation (Part 1): Assess the clinical activity in participants receiving EOS-448 alone or in combination with iberdomide with or without DEX in participants with RRMM All Parts: Further evaluate the clinical activity according to time-to-events of EOS-448 alone or in combination with iberdomide with or without DEX in participants with RRMM; Assess the PK and immunogenicity of EOS-448 (alone or in combination with iberdomide with or without DEX) in blood Exploratory All Parts: To further assess clinical activity in terms of overall survival;T o assess the pharmacodynamic (PD) activity of EOS-448 (alone or in combination with iberdomide with or without DEX) as well as other exploratory biomarkers in blood and bone marrow aspirate samples; To Assess Minimal Residual Disease (MRD) in complete and very good partial responders Expansion (Part 2): In Part 2 (Arms 2B and 2C), to assess PK of iberdomide (in combination with EOS-448 with or without DEX) in blood samples;Primary end point(s): - Incidence of dose limiting toxicities (DLTs), treatment emergent adverse events (TEAEs), serious adverse events (SAEs), changes in vital signs, electrocardio | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall response (stringent Complete Response [sCR] + Complete Response [CR] + Very Good Partial Response [VGPR] + Partial Response [PR]) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria - Progression-free survival (PFS), duration of response (DoR) and time to response (TTR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria - Summary measures of PK parameters of EOS-448, and incidence of anti-drug antibodies (ADA) to EOS-448;Timepoint(s) of evaluation of this end point: Table 8: Schedule of Assessment – Part 1 Table 9: Schedule of PK/PD sampling timepoints – Part 1 Table 10: Schedule of Assessment Part 2 — Expansion Table 11: Schedule of PK/PD sampling timepoints – Part 2 | — |
Countries
Belgium, France, United States
Contacts
Public ContactClinical Trials Department
iTeos Belgium SA
Outcome results
None listed