A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of CN201

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This study aims to provide a basis for further clinical development of CN201.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Curon Biopharmaceutical (Shanghai) Co.,Ltd

Criteria

Inclusion/Exclusion Criteria:

Inclusion Criteria (Patients who meet all of the following criteria may be enrolled in this clinical study)

1. Males or females aged ≥ 18 to ≤ 75 years.

2. Patients with relapsed or refractory B-NHL. These patients disease history must meet the following World Health Organization (WHO) diagnostic subtypes of B-NHL that are CD19-positive in pathologic Immunohistochemistry test: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) (Grade I to III), marginal zone lymphoma, lymphoplasmacytic lymphoma, mantle cell lymphoma, small lymphocytic lymphoma, and transformed large B-cell lymphoma (During the dose-escalation phase, patients other than those treated with CAR-T who cannot provide proof of pathologic immunohistochemistry CD19 positivity but have previous proof of CD20 positivity may be considered for enrollment after discussion with the sponsor.).

• "Relapse" is defined as the occurrence of PD (progression at primary site or new onsets at other sites) after complete response (CR) or partial response (PR) has been achieved after adequate treatment. Note: For DLBCL patients, relapse must occur after patients undergoing at least two lines of therapy; for other patients, they must undergo at least one line of therapy.

• "Refractory" is defined as a situation that there is no standard of care available or that it is not applicable to use standard of care at this stage, including:

1. Patients who are unresponsive to standard of care (e.g., monotherapy or combination therapy containing anti-CD20 monoclonal antibody) and whose best response to standard therapy is PD or stable disease (SD).

2. Patients who are not eligible for autologous hematopoietic stem cell transplantation (ASCT) and have relapsed PD after receiving ASCT.

3. Patients who have failed on chimeric antigen receptor T cell (CAR-T) immunotherapy, but the first dose of the IMP must be at least 3 months after discontinuation of CAR-T therapy, and CD19 positive expression is still present in tumor tissue.

3. Patients with at least one evaluable tumor lesion per the Lugano 2014 criteria, i.e., a lymph node lesion > 15 mm in long diameter or an extranodal lesion > 10 mm in long diameter according to computed tomography (CT) cross-sectional imaging or MRI.

4. Patients with an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2 and an estimated survival time of more than 3 months.

5. Patients with essentially normal bone marrow function (no blood transfusion within 14 days prior to first dose), including: PLT ≥ 75 × 10 ^ 9/L, absolute neutrophil count (ANC) ≥ 1.5 × 10 ^ 9/L, absolute peripheral blood lymphocyte count (ALC) ≥ 200/μL, and hemoglobin (Hgb) ≥ 9.0 g/dL.

6. Patients with essentially normal coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal (ULN); international normalized ratio (INR) ≤ 1.5 × ULN.

7. Patients with essentially normal function of liver, kidney, lung, and heart function:

1. Liver function: serum total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN unless there is evidence of Gilbert's syndrome); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5.0 × ULN if liver function is affected by any secondary changes caused by tumor);

2. Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 50 mL/min (calculated according to the criteria used by the actual measurement center);

3. Echocardiography: left ventricular ejection fraction (LVEF) ≥ 50%, no pericardial effusion;12-lead electrocardiogram (ECG) results: no clinically significant ECG abnormalities [atrial fibrillation of any grade, type II atrioventricular block of second degree, or third-degree atrioventricular block, or QTcF > 470 msec (female) or > 450 msec (male); other uncontrolled symptomatic arrhythmia];

4. No clinically significant pleural effusion and/or fluid in the abdomen;

5. Oxygen saturation > 92% (without oxygen inhalation).

8. Patients must provide informed consent prior to the initiation of the study and voluntarily sign a written ICF.

9. Female patients of childbearing potential must have a negative blood or urine pregnancy test within 7 days prior to the first dose of the IMP; patients of childbearing potential (males and females) must agree to use reliable methods of contraception (hormonal or barrier methods or sexual abstinence) with their partner after signing the ICF until 90 days after the last dose.

Exclusion Criteria (Patients who meet any of the following exclusion criteria will not be included in this study)

1. Patients with any other non-Hodgkin lymphoma (NHL) not listed in inclusion criteria (2).

2. Patients treated with anti-CD3/CD19 bispecific antibody (BsAb) prior to first dose of IMP (After discontinuing treatment with the IMP, subjects in the 2.5 μg/dose and 5 μg/dose groups of this study may have one opportunity to participate in the higher dose group after eluted for 5 half-lives of the drug, provided that the patient will benefit from the high dose group as assessed by the investigator, and that the participation is in accordance with the patient's wishes, and approved by the Sponsor).

3. Patients who have received chemotherapy, endocrine therapy , radiotherapy (palliative radiotherapy 2 weeks prior to the first administration of the investigational drug), or biologic therapy, and small molecule targeted agents within 2 weeks prior to the first administration of the investigational drug or within 5 half-lives of the drug, whichever is shorter. Patients who have received anti-CD20 antibody or anti-CD19 antibody within 4 weeks prior to first use of the investigational drug.

4. Patients who have received anti-tumor immunotherapy or other unlisted clinical IMP within 4 weeks prior to the first dose of IMP, or within 5 half-lives of the drug, whichever is shorter.

5. Patients who have undergone any major organ surgery (excluding aspiration biopsy) or significant trauma within 4 weeks prior to the first dose of the IMP, or those requiring elective surgeries during the study.

6. Patients who have received systemic corticosteroids (prednisone >10 mg/day or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of the IMP, excluding the following agents: topical, ocular, intra-articular, intranasal, and inhaled corticosteroids, and short-term, prophylactic use of corticosteroids (eg, to prevent radio contrast agent induced allergic reactions).

7. Patients who have used immunomodulatory agents, including but not limited to thymosin, interleukin-2 (IL-2), interferon (IFN) and anti-tumor Chinese patent drugs or Chinese herbal medicines, etc., within 14 days prior to the first dose of the IMP.

8. Patients who have used live attenuated vaccines within 4 weeks prior to the first dose of the IMP.

9. Patients with central nervous system (CNS) infiltration.

10. Patients with previous or concomitant CNS diseases, including: epilepsy, hemorrhagic/ischemic stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disorder, organic cerebellar syndrome, mental diseases, etc.

11. Patients with prior or concomitant malignancies (except cured basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, prostatic intraepithelial neoplasia, and other tumors that have been clinically cured for 5 years as assessed by the investigator).

12. Patients with uncontrolled active infections currently requiring systemic anti-infective therapy within 3 days prior to first dose.

13. Patients with active hepatitis B and/or hepatitis C. Patients who are positive for antibodies to hepatitis C virus (HCV). Patients with hepatitis B surface antigen (HBsAg) was not allowed to enroll in the dose-escalation period; however, those who were hepatitis B surface antigen (HBsAg)-positive but HBVDNA-negative and adherent to entecavir antiviral therapy and who agreed to regular monitoring of HBVDNA were allowed to enroll in the dose-expansion period.

14. Patients with a history of immunodeficiency, including those who are tested positive for human immunodeficiency virus (HIV) antibody.

15. Patients with a history of serious cardiovascular and cerebrovascular disease, including but not limited to:

1. Patients with severe cardiac rhythm or conduction abnormalities;

2. Patients with acute coronary syndrome, congestive heart failure, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to the first dose;

3. Patients with ≥ Class II cardiac function as per New York Heart Association (NYHA) functional class or LVEF < 50%;

4. Patients with clinically uncontrollable hypertension.

16. Patients with previous or current interstitial lung disease.

17. Patients with acute graft-versus-host disease (GVHD) or active chronic GVHD at present.

18. Patients with active or history of autoimmune diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, vasculitis, psoriasis, etc.) that may relapse, or patients who are at risks (e.g., organ transplant requiring immunosuppressive therapy). However, patients with the following diseases are allowed to be further screened for enrollment: hypothyroidism managed with hormone replacement therapy only, and skin diseases not requiring systemic treatment (such as vitiligo, psoriasis, or alopecia).

19. Patients who have received immunotherapy and experienced Grade 3 or higher immune-related adverse events (irAEs).

20. Patients whose non-hematologic adverse reactions from prior anti-tumor therapy have not recovered to Grade ≤ 1 as assessed by NCI-CTCAE Version 5.0 (excluding toxicities such as alopecia that are assessed by the investigator to have no safety risk).

21. Patients with known alcohol or drug dependence.

22. Patients with mental disorders or poor protocol compliance.

23. Pregnant or lactating women.

24. Patients that are considered ineligible for this study by the investigator for other reasons.