lymphoma NHS Non-Hodgkin Lymphoma
Conditions
Interventions
BYON4228 will be given by intravenous infusion. Different doses of BYON4228
will be given to different patients. The first patient will receive the lowest
dose 7 mg and will be escalated for the fol
Sponsors
Byondis Bv.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: 1. Male or female, age >= 18 years at the time of signing informed consent; 2. Patient with: a. Part 1 only: (Aggressive or indolent) B-cell NHL expressing CD20 by immunohistochemistry (IHC) or flow cytometry, R/R to at least 2 prior lines of therapy or autologous CAR-T cell therapy; b. Part 2 cohort A only: Histologically confirmed aggressive B cell NHL (e.g., DLBCL, MCL) expressing CD20 by IHC or flow cytometry, R/R to frontline therapy, or second line salvage regimens or autologous hematopoietic cell transplantation, or autologous CAR-T therapy; c. Part 2 cohort B only: Histologically confirmed indolent B-cell NHL (e.g., marginal zone, follicular lymphoma (Grade 1-3a) expressing CD20 by IHC or flow cytometry, R/R to at least 2 prior lines of therapy; For both parts: autologous hematopoietic stem cell transplantation (HSCT) and autologous CAR-T cell therapy (if more than 3 months prior to start IMP), and allogeneic HSCT (if more than 6 months prior to start IMP) are allowed as prior lines. 3. Eastern Cooperative Oncology Group (ECOG) performance status = 8.5 g/dL (> 5.28 mmol/L); b. Absolute neutrophil count (ANC) >= 1.0 × 109/mL; c. Platelet counts >= 50 × 109/mL; If bone marrow involvement: >= 25 × 109/mL; 6. Laboratory measurements, hepatic function: a. Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) 30 mL/min/1.73 m2 (calculated with CKD-EPI formula); 8. Females of childbearing potential must be willing to use a highly effective method of contraception during the study and for 12 months after the last dose of rituximab or for 6 months after the last dose of BYON4228, whichever takes longer; 9. Part 1: Willing to consent to 1 pre-treatment tumor biopsy. If a recent (
Exclusion criteria
Exclusion criteria: 1. Having been treated with: a. CD47 or SIRPa targeting agents at any time; b. Other anticancer therapy including investigational agents within 2 weeks prior to start of BYON4228 treatment or within 4 times the elimination half-life (up to a maximum of 4 weeks) whichever is longer. Note: treatment with hormonal therapy with LHRH agonists for localized prostate cancer, and treatment with bisphosphonates and RANKL inhibitors are not criteria for exclusion; c. Radiotherapy within 1 week prior to start of BYON4228; d. Autologous HSCT or CAR-T cell therapy within 3 months prior to start IMP, or allogeneic HSCT within 6 months prior to start IMP. In addition, the patient must have sufficiently recovered from any treatment-related toxicities or CTCAE Grade
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoints The primary endpoint for Part 1 of the trial is: • Incidence of dose limiting toxicity (DLT), or • Optimal biological dose (OBD). The primary endpoint for Part 2 of the study is: • Objective response rate (ORR). Optimal biological dose (OBD) is defined as the dose level where no DLTs were experienced, providing maximal target engagement over the full dosing interval (28 days for the 4-weekly cohorts, 14 days for the 2-weekly cohorts) an acceptable benefit/risk profile for all evaluable patients in the dose-cohort. Objective response rate (ORR) is defined as the percentage of patients with a best overall tumor response of complete response (CR) or partial response (PR) according to the Lugano classification. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety endpoints The endpoints related to safety include: • Incidence and severity of (serious) AEs; • Changes in vital signs and weight; • Changes in ECOG performance status; • Changes in laboratory parameters; • Percentage of patients with confirmed anti-BYON4228 and anti-rituximab antibodies; • Number of patients with dose modifications due to AEs. Efficacy endpoints Preliminary efficacy will be assessed by: • ORR (Part 1); • Clinical benefit rate (CBR); • Number of patients with CR, PR, stable disease (SD) and progressive disease (PD); • Best percent change in target lesion measurements; • Time to response; • Duration of response (DOR); • Progression-free survival (PFS); • Overall survival (OS). Clinical benefit rate (CBR) is defined as the percentage of patients with CR, PR, SD or non-CR/non-PD (SD or non-CR/non-PD for 6 or more months). Time to response (TTR) is defined as the time from first day of IMP treatment to first observation of CR or PR. Duration of response (DOR) is defined as the duration from first observation of response (CR or PR) to the time of disease progression or death from any cause. Progression-free survival (PFS) is defined as the time from first day of IMP treatment to disease progression or death from any cause. All above described responses will be calculated using the Lugano classification first and subsequently using the LYRIC criteria. Overall survival (OS) is defined as the time from first day of IMP treatment to death from any cause. 14.2.3. Pharmacokinetic endpoints PK endpoints will include standard parameters such as Cmax, tmax, area under the curve (AUC), Cmin (trough-levels), terminal half-life (t*), volume of distribution, and drug clearance. 14.2.4. Other endpoints The exploratory pharmacodynamic and predictive biomarker endpoints will include, but are not limited to: • SIRPa receptor occupancy (RO) on peripheral blood monocytes over time; • Tumor DNA/RNA whole exome sequencing; • Bl | — |
Countries
Netherlands
Outcome results
None listed