A Phase I/II Study of CM355 in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL)

Study Overview
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Brief Summary
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A Phase I/II Open-Label, Single-Arm, Multicenter Clinical Study of CM355 in Patients With R/R B-NHL

Detailed Description
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This is a phase I/II open-label, single-arm, multicenter study in China to evaluate the safety, tolerability, and efficacy of CM355 in patients with R/R B-NHL. In the study, patients will not be screened for CD20 expression, but they must have a diagnosis of B-NHL that is expected to express CD20. After enrollment, tumor samples will be collected for retrospective analysis of CD20 expression

Official Title
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A Phase I/II Open-Label, Single-Arm, Multicenter Clinical Study of CM355 in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma (B-NHL)

Conditions
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Hematoma

Intervention / Treatment
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* Drug: CM355


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged ≥ 18 years old. Eastern Cooperative Oncology Group (ECOG, see Appendix 3) PS score of 0-1. Histopathologically confirmed relapsed or refractory B-cell NHL has been confirmed or anticipated to express CD20 in lymphoma lesions. According to Lugano criteria, imaging evaluation shows at least one bidimensionally measurable lesion. The level of organ function of patients must In line with the testing standard of the clinical trial center prior to the first dose of the investigational drug Expected survival ≥ 3 months. All toxicities caused by prior anticancer therapy must have recovered to grade ≤ 1 (based on CTCAE v5.0) except alopecia and fatigue. Female patients with childbearing potential should have a negative blood pregnancy test result within 7 days prior to the first dose. Female patients with childbearing potential or male patients and their partners must agree to take effective contraceptive measures from the signing of the ICF to at least 6 months after the last dose of investigational drug. Female patients cannot breastfeed or plan to become pregnant during the study until at least 6 months after the last dose of investigational drug. The patient voluntarily joined the study and signed the ICF. Exclusion Criteria: Active or past central nervous system (CNS) lymphoma. Other active malignancies occurring within 5 years prior to the first dose of investigational drug, with the exception of radically treated local curable cancers. The patient has a disease or medical history that needs to be excluded as specified in the Clinical Trial Protocol. Any active infection requiring systemic therapy via intravenous infusion within 14 days prior to the first dose of investigational drug. According to the trial scheme, patients infected with hepatitis B virus, hepatitis C virus, HIV, EBV, CMV, syphilis, or patients with active pulmonary tuberculosis or history of pulmonary tuberculosis infection are not suitable to participate in the study. Any severe or uncontrolled systemic disease. History of severe allergic reactions (CTCAE v5.0 classification is greater than 3 grades) to humanized monoclonal antibodies, or known hypersensitivity to any component of CM355. Any mental or cognitive disorder that may limit the patient's understanding and execution of the ICF and compliance with the study. Medication history and surgical history: Having received allogeneic hematopoietic stem cell transplantation or received auto-HSCT within 100 days prior to the first dose. Active bleeding within 2 months prior to screening, or receiving anticoagulants, or other bleeding symptoms requiring medical intervention. Having undergone major surgery within 28 days prior to the first dose, or minor surgery within 2 weeks prior to the first dose; invasive examinations for the purpose of diagnosis are not considered as surgery; except for the insertion of vascular access device. Patients who experienced grade ≥ 3, severe or life-threatening immune-related adverse events or grade 1-2 immune-related adverse events that did not return to baseline levels after treatment discontinuation in a previous immunotherapy. Patients who have received any other investigational anti-cancer drug therapy within 28 days prior to the first dose. Inoculation of live attenuated vaccines within 28 days prior to the first dose, or anticipation that live attenuated vaccines will be required during the study. Patients who have received any drugs therapy that need to be excluded from the Clinical Trial Protocol within a certain period of time for the first administration. Prior participation in other clinical trials within 28 days prior to the first dose of the investigational drug, or planning to participate in this study and other clinical trials at the same time. Known alcoholism or drug abuse history. Other conditions determined by the investigator that render patients unsuitable for participation in this study.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CM355<br>Dose Escalation Phase CM355 Dose Expansion Phase CM355 | Drug: CM355<br>* Dose Escalation Phase CM355 will be taken by patients and will be treated follow the 3+3 dose escalation scheme Expansion Phase CM355 will be taken by patients and will assess the efficacy of CM355 in patients with specific histopathological Non-Hodgkin's Lymphoma, and the safety of drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities (DLT) | Incidence, nature, and severity of dose-limiting toxicities. | Up to 2 year | 
| Recommended phase II dose (RP2D) and/or (maximum tolerated dose) MTD | To determine the recommended phase II dose (RP2D) and/or the maximum tolerated dose (MTD) of CM355 in patients with R/R B-NHL. | Up to 2 year | 
| Objective response rate（ORR） | Objective response rate (ORR) as assessed by independent review committee (IRC) | through study completion，an average of 5 year | 
| The safety and tolerability of CM355 | Incidence, nature, and severity of adverse events (AEs) as judged according to NCI-CTCAE v5.0. | through study completion，an average of 5 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Dose Escalation peak plasma concentration (ng/mL) | Every cycle (21 days), until the end of treatment | 
| Area under the plasma concentration versus time curve (AUC) | Dose Escalation AUC（μg·h/mL） | Every cycle (21 days), until the end of treatment | 
| Peak time | Time of maximum observed plasma concentration (Tmax) | Every cycle (21 days), until the end of treatment | 
| T1/2 | Terminal half-life of CM355 | Every cycle (21 days), until the end of treatment | 
| Clearanc (CL) | Total body clearance of the drug from plasma (CL) of CM355 | Every cycle (21 days), until the end of treatment | 
| Anti-CM355 antibodies (ADAs) | Incidence of anti-CM355 antibodies (ADAs) and their correlation with clinical outcomes. | Every cycle (21 days), until the end of treatment | 
| Objective response rate (ORR) | Objective response rate (ORR) as assessed by investigators | through study completion，an average of 5 year | 
| Complete response rate (CRR) | Complete response rate (CRR) as assessed by investigators or independent review committee (IRC) | through study completion，an average of 5 year | 
| Duration of response (DOR) | Duration of response (DOR) as assessed by investigators or Independent review committee (IRC) | through study completion，an average of 5 year | 
| Progression-Free-Survival (PFS) | Progression-Free-Survival (PFS) as assessed by investigators or independent review committee (IRC) | through study completion，an average of 5 year | 
| overall survival (OS) | overall survival (OS) as assessed by investigators or independent review committee (IRC) | through study completion，an average of 5 year |