A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN1

Study Overview
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Brief Summary
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This study is the first-in-human clinical trial of CN1 to evaluate the safety, tolerability, pharmacokinetic (PK) profile and preliminary efficacy of CN1 in patients with advanced solid tumors or B-cell lymphoma. This study will provide a basis for further clinical development of CN1.

Detailed Description
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CN1 could promote T cell activation and cytokine secretion, thereby enhancing the function of CD4+ and CD8+ T cells, and could also regulate Treg cells, thus CN1 is considered to enhance the anti-tumor immune response and have potential antitumor activity. In this multicenter, open-label, dose-escalation Phase I study six dose levels are planned. Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). After completion of treatment cycles, the participant will be assessed by the Principal Investigator and/or Safety Monitoring Committee (SMC).

Official Title
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A Phase I, Open Label, Multi-Center, Dose Escalation Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN1 in Patients With Advanced Solid Tumors or B-cell Lymphoma

Conditions
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Advanced Solid Tumor, B Cell Lymphoma

Intervention / Treatment
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* Drug: CN1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years and ≤ 75 years old, male or female; Subjects with histologically or cytologically diagnosed advanced malignant solid tumors or B-cell lymphoma who have failed on, or are intolerant to, standard therapy, for whom there are no standard of care regimens, or who are otherwise not eligible for standard therapy at this stage; Subjects with Eastern Cooperative Oncology Group (ECOG) performance score of 0-1; Females must be non-pregnant and non-lactating, and must use an acceptable, highly effective double contraception from screening until the end of the follow-up period. Subjects must be able to understand and sign the paper informed consent before any study specific procedure. Exclusion Criteria: Received anti-tumor treatment such as radiotherapy, chemotherapy, biotherapy, endocrine therapy, immunotherapy, etc., within 4 weeks prior to the first dose of study drug. Received other investigational agents (not yet approved by any regulatory agency) within 4 weeks prior to the first dose of study drug; Major organ surgery (excluding puncture biopsy) or significant trauma within 4 weeks prior to the first dose of study drug; Systemic application of corticosteroids (prednisone > 10 mg/day or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of study drug; Exceptions: topical, ocular, intra-articular, intranasal, and inhaled corticosteroids, or short-term corticosteroids for prophylaxis (e.g., contrast allergy prophylaxis). Use of live attenuated vaccine within 4 weeks prior to the first dose of study drug; Clinically symptomatic metastases to the central nervous system or meninges, or other evidence of uncontrolled metastases to the central nervous system or meninges of the subject; Active infection and in current need of, or likely to need, intravenous anti-infective therapy; History of immunodeficiency, including history of any positive test result for human immunodeficiency virus (HIV) antibody; Active hepatitis B or hepatitis C virus infection. Subjects with active or previous autoimmune diseases (e.g. systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), except subjects with clinically stable autoimmune thyroid disease; Subjects with mental disorders or other conditions that pose high non-compliance risks in the opinion of the investigator;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single Arm<br>Five planned CN1 dose levels of 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg. Subjects will receive CN1 by intravenous infusion (IV) on Day 1 (D1) of each cycle (once every 3 weeks per cycle). | Drug: CN1<br>* Participants will receive CN1 by IV infusion on Day 1 of each cycle (every 3 weeks). The 5 planned dose levels are 0.03 mg/kg, 0.3 mg/kg, 1 mg/kg, 3 mg/kg and 10 mg/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and/or recommended Phase II dose (RP2D) of CN1 administered to patients with advanced solid tumor or B-cell lymphoma. | DLT is measured in the observation period of 21 days after the first dose i.e. starting dose level 0.03 mg/kg. if the enrolled subject does not experience a study drug related Grade 2 or higher adverse event (AE) per NCI-Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, the subject will start to receive the next designated dose level of 0.3 mg/kg in the second 21 days dosing cycle. | 21 Days after the first dose i.e. starting dose level 0.03 mg/kg | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Physical Exam | Measured by incidence of abnormal physical examination findings. | From baseline(Week 1) to 90 days after the last dose | 
| To assess the safety and tolerability of CN1 in patients with advanced solid tumor or B-cell lymphoma through Adverse Events/Serious Adverse Events | Measured by incidence of Adverse Events/Serious Adverse Events. All AEs will be summarized according to the Medical Dictionary for Regulatory Activities (MedDRA) v23.0 or higher and the severity will be categorized by CTCAE v5.0. The summary of all AEs will be focused on the treatment-emergent adverse events (TEAEs). A TEAE is defined as any AE that starts after the first dose of study drug till 90 +/- 7 days after the last dose of study drug. | From baseline(Week 1) to 90 days after the last dose | 
| To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Area under the plasma concentration-time curve | The following parameter is used for evaluation during PK assessments: Area under the plasma concentration-time curve (AUC0-t, AUC0- ∞, AUC0-τ) | Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. | 
| To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Tmax | The following parameter is used for evaluation during PK assessments: Time to maximum (Tmax) | Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. | 
| To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Apparent volume of distribution at steady state | The following parameter is used for evaluation during PK assessments: Apparent volume of distribution at steady state (Vss) | Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. | 
| To assess the pharmacokinetic (PK) profile of CN1 in patients with advanced solid tumor or B-cell lymphoma through Accumulation factor based on AUC 0-τ | The following parameter is used for evaluation during PK assessments: Accumulation factor based on AUC 0-τ (R AUC0-τ) | Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. | 
| To assess the immunogenicity to CN1 in patients with advanced solid tumor or B-cell lymphoma through ADA testing | A validated analysis method will be used for detection of anti-drug antibodies (ADA). | Measurement is through treatment completion starting from Week 1 up to End of Treatment, assessed up to an average of 10 weeks. | 
| To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through ORR analysis | Assessed by the number of participants with objective response (ORR) | Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first. | 
| To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DCR analysis. | Assessed by the number of participants with Disease Control (DCR) | Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first. | 
| To explore the anti-tumor efficacy of CN1 in patients with advanced solid tumor or B-cell lymphoma through DoR analysis. | Assessed by the number of participants with Duration of Response (DoR) | Measurement is from Week 1, until the 90 days after the last dose, date of first documented progression or unacceptable toxicity, withdrawal of consent, subject being lost to follow-up, or death, whichever occurs first. |