A Trial of SHR-A1912 Combined With Other Therapies in B-cell Non-Hodgkin 's Lymphoma

Study Overview
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Brief Summary
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This study aims to evaluate the safety, PK and preliminary anti-tumour activity of SHR-A1912 combined with other therapies in patients with B-cell non-Hodgkin 's lymphoma.

Official Title
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A Phase Ib/II Study of SHR-A1912 Combined With Other Therapies in Patients With B-cell Non-Hodgkin 's Lymphoma

Conditions
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B-cell Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: SHR-A1912; R-Chemo
* Drug: SHR-A1912; R-Chemo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to18 years old; Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 1; Life expectancy >3 months; Histologically confirmed B-cell B-cell non-Hodgkin's lymphoma; Previous systematic anti-tumor therapy should meet the following requirements: 1) Relapsed and/or refractory disease after at least one (≥ 1) line of prior systemic therapy (relapsed/refractory cohort); 2) Previously untreated (naïve cohort). At least one measurable nodal lesion, defined as > 1.5 cm in its longest dimension, or one measurable extra nodal lesion, defined as > 1.0 cm in its longest diameter. Exclusion Criteria: Received autologous stem cell transplantation within 12 weeks before the first study treatment; previously received allogeneic stem cell transplantation; received Car-T cell therapy within 12 weeks before the first study treatment; History of recent major surgery or severe trauma within 4 weeks before the first study treatment; Received anti-tumour treatment within 2 weeks before the first study treatment; Central nervous system (CNS) infiltration; Active infection with HBV or HCV; History of immunodeficiency, including HIV serotest positive, or other acquired or congenital immunodeficiency diseases, and active tuberculosis; Active infection or unexplained fever>38.5℃; History of severe cardiovascular disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An open, multicenter, dose-finding and dose expansion investigational Phase Ib/II clinical trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-A1912 combined with R-Chemo (Phase 1b)<br> | Drug: SHR-A1912; R-Chemo<br>* SHR-A1912 combined with R-Chemo: SHR-A1912 + R-Chemo (Rituximab + Chemotherapy) (Phase 1b)<br>|
| Experimental: SHR-A1912 combined with R-Chemo (Phase 2)<br> | Drug: SHR-A1912; R-Chemo<br>* SHR-A1912 combined with R-Chemo: SHR-A1912 (RP2D) + R-Chemo (Rituximab + Chemotherapy) (Phase 2)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: RP2D (Recommended Phase II Dose) of SHR-A1912 combined with immunochemotherapy |  | The RP2D for Phase 2 will be selected at the end of Phase 1b, approximately 12 months | 
| Phase 1b: Incidence and severity of AE |  | Up to follow-up period, approximately 24 months] | 
| Phase 2: Objective response rate |  | assessed up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1b: Objective response rate |  | assessed up to approximately 24 months | 
| Phase 1b: Complete response rate (CRR) |  | assessed up to approximately 24 months | 
| Phase 1b: Duration of remission (DoR) |  | assessed up to approximately 24 months | 
| Phase 1b: Progression-free survival (PFS) |  | assessed up to approximately 24 months | 
| Phase 1b: Toxin binding antibody to SHR-A1912 |  | Up to follow-up period, approximately 24 months | 
| Phase 1b: Total antibody to SHR-A1912 |  | Up to follow-up period, approximately 24 months | 
| Phase 1b: Concentration of free toxin |  | Up to follow-up period, approximately 24 months | 
| Phase 1b: Anti-drug antibodies (ADA) to SHR-A1912 |  | Up to follow-up period, approximately 24 months | 
| Phase 2: Complete response rate (CRR) |  | assessed up to approximately 24 months | 
| Phase 2: Duration of remission (DoR) |  | assessed up to approximately 24 months | 
| Phase 2: Progression-free survival (PFS) |  | assessed up to approximately 24 months | 
| Phase 2: Incidence and severity of AE |  | Up to follow-up period, approximately 24 months | 
| Phase 2: Toxin binding antibody to SHR-A1912 |  | Up to follow-up period, approximately 24 months | 
| Phase 2: Total antibody to SHR-A1912 |  | Up to follow-up period, approximately 24 months | 
| Phase 2: Concentration of free toxin |  | Up to follow-up period, approximately 24 months | 
| Phase 2: Anti-drug antibodies (ADA) to SHR-A1912 |  | Up to follow-up period, approximately 24 months |