A First-in-human Study of SCTB35 in Patients With Relapse/Refractory B-cell Non-Hodgkin Lymphoma

A Phase Ia/Ib Dose-escalation and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SCTB35 in Patients With CD20+ Relapse/Refractory B-cell Non-Hodgkin Lymphoma

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Hodgkin Lymphoma, B-cell
• Intervention / Treatment: Drug: SCTB35 injection

Detailed Description

This is the first-in-human study of SCTB35, containing the dose-escalation and dose-expansion parts. The escalation cohorts will be enrolled to explore the maximum tolerated dose and recommended phase II dose (RP2D). A Safety Monitoring Committee (SMC) will review the accumulated safety data and other available data, and make a recommendation to each dose level of SCTB35 in the escalation cohorts. The expansion cohorts will be initiated after the RP2D is confirmed, and to further compare the preliminary efficacy and safety of SCTB35 at two dose levels that appropriately recommended by SMC.

• Study Type: Interventional
• Enrollment (Estimated): 76
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Junfan Ma, Ph.D; Phone Number: 86-010-58628288; Email: junfan_ma@sinocelltech.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital
      • Contact: Yuqin Song, M.D.; Phone Number: 010-88196118; Email: SongYQ_VIP@163.com
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
      • Contact: Keshu Zhou, M.D.; Phone Number: 13674902391; Email: dr_zkshu23810@163.com
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute & Hospital
      • Contact: Lanfang Li, M.D.; Phone Number: 18622221613; Email: lilanfangmeng@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SCTB35; SCTB35 injection is subcutaneously given every week for the first 4 cycles, and thereafter every 3 weeks. Cycles will be repeated every 3 weeks until disease progression, study discontinuation, or death, whichever occurs first.	Drug: 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.; Other Names: none other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-escalation part: incidence rate of adverse event (AE)	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)	From first dose until 28 days after last dose of study drug or until study completion or participant withdrawal (up to 3 years)
Dose-expansion part: objective response rate (ORR)	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	From first dose until up to 2 years
Dose-escalation part: dose limited toxicity (DLT)	To determine the maximum tolerated dose (MTD) and/or RP2D to be studied in the dose-expansion part	During the first cycle (21 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-escalation part: ORR	ORR is defined as the percentage of patients achieving CR or PR as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-escalation part: CR rate (CRR)	CR rate is defined as the percentage of patients with CR as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-escalation part: duration of response (DOR)	DOR is defined as the time from first documented objective response to PD or death due to any cause, whichever occurs first, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-escalation part: progression-free survival (PFS)	PFS is defined as the time from first dose to first documented PD or death due to any cause, whichever occurs first, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-escalation part: time to response (TTR)	TTR is defined as the time from first dose to first documented objective response observed for patients who achieved a CR or PR, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-escalation part: overall survival (OS)	OS is defined as the time from first dose to death due to any cause	From first dose until up to 5 years
Dose-escalation part: blood concentrations of SCTB35	The pharmacokinetics of SCTB35 will be analyzed based on the drug concentrations at respective timepoints in the blood samples (or blood derivative)	From first dose until up to 2 years
Dose-escalation part: anti-drug antibodies of SCTB35	Blood samples (or blood derivative) will be screened for antibodies binding to SCTB35	From first dose until up to 2 years
Dose-expansion part: CRR	CR rate is defined as the percentage of patients with CR as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-expansion part: DOR	DOR is defined as the time from first documented objective response to PD or death due to any cause, whichever occurs first, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-expansion part: PFS	PFS is defined as the time from first dose to first documented PD or death due to any cause, whichever occurs first, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-expansion part: TTR	TTR is defined as the time from first dose to first documented objective response observed for patients who achieved a CR or PR, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-expansion part: OS	OS is defined as the time from first dose to death due to any cause	From first dose until up to 5 years
Dose-expansion part: AE	To evaluate the incidence rates of TEAE, TRAE, SAE, AESI	From first dose until up to 2 years
Dose-expansion part: blood concentrations of SCTB35	The pharmacokinetics of SCTB35 will be analyzed based on the drug concentrations at respective timepoints in the blood samples (or blood derivative)	From first dose until up to 2 years
Dose-expansion part: anti-drug antibodies of SCTB35	Blood samples (or blood derivative) will be screened for antibodies binding to SCTB35	From first dose until up to 2 years
Dose-escalation part: best of overall response (BOR)	BOR is defined as the percentage of patients achieving best response from the first dose to first documented disease progression (PD) or new anticancer therapy, whichever occurs first, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years
Dose-expansion part: BOR	BOR is defined as the percentage of patients achieving best response from the first dose to first documented PD or new anticancer therapy, whichever occurs first, as determined by the investigator according to the Lugano Criteria 2014	From first dose until up to 2 years

Collaborators and Investigators

• Sponsor: Sinocelltech Ltd.
• Investigators: Principal Investigator: Yuqin Song, M.D., Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Non-Hodgkin Lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: SCTB35-X101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No