Non-hodgkin's Lymphoma
Conditions
Brief summary
To explore the safety and preliminary efficacy of GNC-038 in patients with relapsed or refractory NHL, and to determine the MTD and RP2D of GNC-038, or the MAD and DLT
Detailed description
phase Ib: To explore the safety and preliminary efficacy of GNC-038 in patients with relapsed or refractory NHL, and to determine the MTD and RP2Dof GNC-038, or the MAD and DLT of GNC-038 if MTD is not reached, by intravenous infusion (IV, QW) once a week (2 weeks as a cycle) phase II To explore the efficacy of GNC-038 in patients with relapsed or refractory non-Hodgkin's lymphoma
Interventions
DRUGGNC-038
Administration by intravenous infusion
Sponsors
Sichuan Baili Pharmaceutical Co., Ltd.
SystImmune Inc.
Baili-Bio (Chengdu) Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. The subject is capable of understanding the informed consent form, voluntarily participates, and signs the informed consent form; 2. No gender restrictions; 3. Age: ≥18 years and ≤75 years; 4. Expected survival time ≥3 months; 5. Patients with histologically confirmed non-Hodgkin's lymphoma; 6. Patients with relapsed or refractory non-Hodgkin's lymphoma (R/R NHL); 7. Presence of measurable lesions during the screening period (lymph node lesions with any long diameter ≥1.5 cm or extranodal lesions with any long diameter \>1.0 cm); 8. ECOG performance status score ≤2; 9. Adverse reactions from prior anti-tumor treatment have recovered to ≤Grade 1 as per CTCAE 5.0 criteria; 10. Organ function levels meet the requirements before the first dose; 11. Female subjects of childbearing potential or male subjects with partners of childbearing potential must use highly effective contraception from 7 days before the first dose until 12 weeks after treatment discontinuation. Female subjects of childbearing potential must have a negative serum/urine pregnancy test within 7 days before the first dose; 12. The subject has the ability and willingness to comply with the study protocol-specified visits, treatment plans, laboratory tests, and other study-related procedures.
Exclusion criteria
1. Pulmonary diseases classified as ≥Grade 3 according to NCI-CTCAE v5.0; patients currently diagnosed with interstitial lung disease (ILD); 2. Active infections requiring systemic treatment, such as severe pneumonia, bacteremia, sepsis, etc.; 3. Active tuberculosis; 4. Patients with active autoimmune diseases; 5. History of other malignancies within 5 years prior to the first dose; 6. HBsAg-positive and/or HBcAb-positive with HBV-DNA levels ≥ the lower limit of detection; HCV antibody-positive with HCV-RNA levels ≥ the lower limit of detection; HIV antibody-positive; 7. Poorly controlled hypertension (systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg); 8. History of severe cardiovascular or cerebrovascular diseases; 9. Patients with a history of hypersensitivity to recombinant humanized antibodies or any excipients of GNC-038; 10. Pregnant or lactating women; 11. Patients with central nervous system involvement; 12. Major surgery within 28 days before the first dose of this study or planned major surgery during the study period; 13. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation (Allo-HSCT); 14. Autologous hematopoietic stem cell transplantation (Auto-HSCT) within 12 weeks before initiating GNC-038 treatment; 15. Current use of immunosuppressive therapy; 16. Radiotherapy within 4 weeks before initiating GNC-038 treatment; 17. Chemotherapy or small-molecule targeted therapy within 2 weeks or 5 half-lives prior to treatment; 18. CAR-T therapy within 12 weeks before initiating GNC-038 treatment; 19. Use of any other investigational drug in a clinical trial within 4 weeks or 5 half-lives before the first dose of this study; 20. Any other condition deemed unsuitable for participation in this clinical trial by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limiting toxicity (DLT) | Up to 14 days after the first dose | The incidence and severity of adverse events (TEAE) during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0). |
| Maximum tolerated dose (MTD) or Maximum dose (MAD) | Up to 14 days after the first dose | In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD. |
| Adverse Events during Treatment (TEAE) | Up to approximately 24 months | TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of GNC-038. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-038. |
| Recommended dose for Phase II clinical studies (RP2D) | Up to 14 days after the first dose | The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of GNC-038. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| disease control rate (DCR) | Up to approximately 24 months | Number of patients showing Complete Response (CR) or Partial Response (PR) based on RECIST for the best response. Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response. |
| progression-free survival (PFS) | Up to approximately 24 months | The PFS is defined as the time from the participant's first dose of GNC-038 to the first date of either disease progression or death, whichever occurs first. |
| Adverse Events of Special Interest (AESI) | Up to approximately 24 months | AESI is an event of scientific and medical interest specific to the sponsor's product or research project. |
| Cmax | Up to approximately 24 months | Maximum serum concentration (Cmax) of GNC-038 will be investigated. |
| Tmax | Up to approximately 24 months | Time to maximum serum concentration (Tmax) of GNC-038 will be investigated. |
| AUC0-INF | Up to approximately 24 months | Blood concentration - Area under time line. |
| AUC0-T | Up to approximately 24 months | Blood concentration - Area under time line. |
| T1/2 | Up to approximately 24 months | Blood concentration - Area under time line. |
| anti-drug antibody (ADA) in Ⅰa | Up to approximately 24 months | Frequency and titer of anti-GNC-038 antibody (ADA). |
| DOR (Duration of Response) | Up to approximately 24 months | The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first. |
Countries
China
Contacts
CONTACTSa Xiao, PHD
PRINCIPAL_INVESTIGATORJun Zhu
Peking University Cancer Hospital & Institute
PRINCIPAL_INVESTIGATORYuqin Song
Peking University Cancer Hospital & Institute
Outcome results
None listed