A first-in-human dose escalation and expansion study with the SIRPa-directed monoclonal antibody BYON4228 alone and in combination with rituximab to evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy in patients with relapsed/refractory CD20 positive B-cell Non-Hodgkin*s Lymphoma (NHL)
- Conditions
- lymphomaNHSNon-Hodgkin Lymphoma10025322
- Registration Number
- NL-OMON56086
- Lead Sponsor
- Byondis Bv.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 8
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 <= 1; 4. For Part 2
only: Disease that is measurable or assessable for response per Lugano
Classification for lymphomas; 5. Laboratory measurements, blood counts (Growth
Factor (GF) support and blood transfusions are not allowed within 2 weeks prior
to this assessment): a. Hemoglobin >= 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) < 5 × upper limit of normal (ULN); b.
Total bilirubin <= 1.5 × ULN or 3.0 × ULN and primarily unconjugated if patient
has a documented history of Gilbert*s syndrome or a genetic equivalent; 7.
Laboratory measurements, renal function: Serum creatinine <= 1.5 × ULN or
calculated glomerular filtration rate (GFR) >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 (<= 2 months) archival tumor biopsy
sample is available prior to signing the ICF and the patient did not have
anticancer treatment (including steroids) since the biopsy was performed, this
could be used as the pre-treatment tumor biopsy; 10. Part 2: Willing to consent
to 1 pre-treatment and 1 on-treatment tumor biopsy. If a recent (<= 2 months)
archival tumor biopsy sample is available prior to signing the ICF and the
patient did not have anticancer treatment (including steroids) since the biopsy
was performed, this could be used as the pre-treatment tumor biopsy.
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 <= 1 or baseline, except for
toxicities not considered a safety risk for the patient at the investigator's
discretion;
2. Any contraindication to rituximab treatment;
3. History of hypersensitivity or allergic reaction to any of the excipients of
BYON4228 or rituximab which led to permanent discontinuation of the treatment;
4. Currently diagnosed or suspected CNS involvement;
5. Burkitt's lymphoma;
6. Known active or chronic (DNA or RNA positive) hepatitis B, C or E
infection or human immunodeficiency virus (HIV);
7. Red blood cell (RBC) transfusion dependence, defined as requiring
more than 2 units of RBC transfusions during the 4-week period prior to
screening;
8. Patients with active graft versus host disease (GVHD) or ongoing
immunosuppression for GVHD;
9. History of autoimmune hemolytic anemia or autoimmune
thrombocytopenia that in the investigator's opinion is likely to
jeopardize patient safety;
10. History of autoimmune disorders (including but not limited to:
Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus
erythematosus, Grave's disease) or other conditions that compromise or impair
the immune system (except for hypogammaglobulinemia) and that in the
investigator's opinion is likely to jeopardize patient safety;
11. Second malignancy, other than the one treated in this trial, in the
last 3 years before signing ICF. Except, if appropriately treated: basal
cell or localized squamous skin carcinomas, localized prostate cancer or
localized cervical cancer. Any other indolent malignancy may be allowed upon
discussion with the medical monitor;
12. History (within 6 months prior to start of BYON4228 treatment) or
presence of clinically significant cardiovascular disease such as unstable
angina, congestive heart failure, myocardial infarction, uncontrolled
hypertension, or cardiac arrhythmia requiring medication. Presence of atrial
fibrilation may be allowed upon discussion with the medical monitor;
13. Severe active infection or other severe uncontrolled systemic disease
(e.g., advanced renal disease, pulmonary, uncontrolled diabetes mellitus,
severely immunocompromised state, or metabolic disease) at screening;
14. Major surgery within 4 weeks prior to start of BYON4228 treatment;
15. Pregnancy or active breastfeeding;
16. Other condition that in the investigator's opinion is likely to
jeopardize patient safety or interfere with the patient's ability to comply
with trial requirements.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method