Starting soon
Phase 1
A First-in-human Study of SCTB35 in Patients With Relapse/Refractory B-cell Non-Hodgkin Lymphoma
Condition(s) studied
Non-Hodgkin Lymphoma, B-cell
Investigational drug(s) / intervention(s)
SCTB35 injection: SCTB35 will be subcutaneously administered at a dose as specified in the respective dose-escalation cohorts. Then, the RP2D and another appropriate dose of SCTB35 will be applied for the dose-expansion cohorts.
Study summary
This is a Phase I clinical study designed to evaluate the safety, tolerability, and pharmacokinetics, and preliminary efficacy of SCTB35 monotherapy, an bispecific antibody, in patients with relapsed and/or refractory B-cell non-Hodgkin lymphoma.
Eligibility
Inclusion Criteria:
Patients are eligible to be included in the study only if all the following conditions are met:
1. Age ≥ 18 years
2. Histologically or cytologically confirmed CD20+ mature B-cell neoplasm
For dose-escalation phase:
1. De novo or transformed diffuse large B-cell lymphoma (DLBCL)
2. High-grade B-cell lymphoma (HGBCL)
3. Primary mediastinal large B-cell lymphoma (PMBCL)
4. Follicular lymphoma (FL)
5. Mantle cell lymphoma
6. Small lymphocytic lymphoma (SLL)
7. Marginal zone lymphoma (MZL) (nodal, extranodal or mucosa associated)
For dose expansion phase:
1. FL cohort: histologic confirmed FL grade 1, 2, or 3a at initial diagnosis without clinical or pathological evidence of transformation
2. LBCL cohort: including histologic confirmed DLBCL, not otherwise specified (NOS), Epstein-Barr virus+ DLBCL, transformed DLBCL from indolent subtypes, HGBCL, NOS, double/triple-hit HGBCL, FL grade 3b, and PMBCL
3. For dose-escalation phase:
Relapsed, progressive and/or refractory disease after adequate systemic therapy containing at least an anti-CD20 monoclonal antibody (e.g. rituximab)
1. Patients must have exhausted or are ineligible for all standard therapeutic options
2. Patients with indolent lymphoma (FL, MZL or SLL) must have a need for treatment initiation based on symptoms and/or disease burden
For dose-expansion phase:
Relapsed, progressive and/or refractory disease following ≥ 2 prior lines of adequate systemic therapy containing at least an anti-CD20 monoclonal antibody (e.g. rituximab)
4. At least 1 measurable site of disease based on computed tomography (CT) or magnetic resonance imaging (MRI) (defined as a clearly nodal lesion with the long axis \> 1.5 cm or extranodal lesion with the long axis \> 1.0 cm). Lesions that have previously received radiotherapy can be considered measurable only after confirming the presence of progression or residual lesions. (for the dose-escalation phase: a evaluable site of disease is allowed).
5. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
6. Adequate hepatic/hematologic/renal/cardiac functions indicated by laboratory values
1. Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L within 7 days before first dose of study drug (without growth factor support). There is an exception for patients with bone marrow involvement in which case ANC must be ≥ 0.75 x 10\^9/L
2. Platelets \> 75 x 10\^9/L within 7 days before first dose of study drug (without growth factor support or transfusion). There is an exception for patients with bone marrow involvement in which case platelets must be ≥ 50 x 10\^9/L
3. Hemoglobin \> 90 g/L within 7 days before first dose of study drug (independent of growth factor support or transfusion).
4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or creatinine clearance ≥ 45 mL/min as estimated by Cockcroft-Gault equation
5. Adequate liver function indicated by: i) Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase ≤ 3 x ULN; ii) Alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase ≤ 3 x ULN; iii) Total bilirubin level ≤ 1.5 x ULN (unless documented Gilbert's syndrome).
6. Left ventricular ejection fraction ≥ 50%;
7. Expected survival time is more than 3 months
Exclusion Criteria:
A patient who conforms to any of the following criteria should be excluded from the study:
1. Any prior therapy with an bispecific antibody of the same class
2. Eligible for high dose chemotherapy with hematopoietic stem cell transplantation (HSCT)
3. Known central nervous system (CNS) involvement by lymphoma
4. Known past or current malignancy other than inclusion diagnosis, with the following exceptions:
1. Cervical carcinoma of Stage Ib or less
2. Non-invasive basal cell or squamous cell skin carcinoma
3. Non-invasive, superficial bladder cancer
4. Prostate cancer with a current prostate-specific antigen (PSA) level \<0.1 ng/mL
5. Any curable cancer with a complete response (CR) of \>2 years duration
5. Known clinically significant cardiac disease, including:
1. Onset of unstable angina pectoris or acute myocardial infarction within 6 months prior to signing Informed Consent Form (ICF)
2. Congestive heart failure prior to signing ICF (meets the criteria of New York Heart Association Classification III or IV)
3. Clinically significant arrhythmia prior to signing ICF
6. History of interstitial lung disease or uncontrolled lung diseases, or evidence of dyspnea at rest or pulse oximetry \< 93% while breathing room air.
7. Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy (including \>20mg/day prednisolone \[or equivalent\], but low-dose prednisolone is allowed). The well controlled autoimmune disease can be enrolled at investigator's discretion, including:
1. Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone
2. Patients with a history of type 1 diabetes mellitus who were well controlled (defined as a screening hemoglobin A1c \< 8% and no urinary ketoacidosis)
3. Patients with skin disease who were not treated with systemic corticosteroid
8. History of seizure disorder or confirmed progressive multifocal leukoencephalopathy (PML)
9. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)
10. Known any major episode of active infection requiring treatment with systemic antibiotics within 2 weeks prior to signing ICF
11. Positive for human immunodeficiency virus (HIV) antibody. Positive for hepatitis B antibody (except for only the positive HBsAb) with detectable hepatitis B virus (HBV) DNA. Positive for hepatitis C antibody with detectable hepatitis C virus (HCV) RNA
12. Chimeric antigen receptor T-cell (CAR-T) therapy within 100 days prior to first SCTB35 administration (only applicable for dose-expansion phase)
13. Autologous HSCT within 100 days prior to first SCTB35 administration, or any prior allogeneic HSCT or solid organ transplantation
14. Received major surgery within 4 weeks prior to first SCTB35 administration, or planned to receive major surgery during the study
15. Received any chemotherapeutic agent, other anti-cancer agent, or investigational drug (monoclonal antibody, radioimmunoconjugate, antibody-drug conjugate or otherwise) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to first SCTB35 administration
16. Exposed to live or live attenuated vaccine within 4 weeks prior to first SCTB35 administration, or planned to receive these vaccines during the study
17. Pregnancy or breast feeding. During the study and for 6 months after last administration of SCTB35, a woman of childbearing potential or a man who is sexually active with a woman of childbearing potential disagrees to practice a highly effective method of birth control.
18. Patient has any condition for that, in the opinion of the investigator, participation could prevent, limit, or confound the protocol-specified assessments
Primary outcome measure(s)
- Dose-escalation part: dose limited toxicity (DLT) — During the first cycle (21 days)
To determine the maximum tolerated dose (MTD) and/or RP2D to be studied in the dose-expansion part
- Dose-escalation part: incidence rate of adverse event (AE) — From first dose until 28 days after last dose of study drug or until study completion or participant withdrawal (up to 3 years)
To evaluate the incidence rates of treatment emergent adverse event (TEAE), treatment-related TEAE (TRAE), serious adverse event (SAE), adverse event with special interest (AESI)
- Dose-expansion part: objective response rate (ORR) — From first dose until up to 2 years
ORR is defined as the percentage of patients achieving complete response (CR) or partial response (PR) as determined by the investigator according to the Lugano Criteria 2014
Trial sites (3)
| Facility | City | Region | Status |
| Beijing Cancer Hospital |
Beijing |
Beijing Municipality |
|
| Henan Cancer Hospital |
Zhengzhou |
Henan |
|
| Tianjin Medical University Cancer Institute & Hospital |
Tianjin |
Tianjin Municipality |
|
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