Recombinant Humanized Anti-CD47/PD-1 Bifunctional Antibody HX009 in Patients With Relapsed/Refractory Lymphoma
- Conditions
- Relapsed/Refractory Lymphoma
- Interventions
- Drug: Recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection
- Registration Number
- NCT05189093
- Lead Sponsor
- Hangzhou Hanx Biopharmaceuticals, Ltd.
- Brief Summary
This study is a multi-center, open, single-arm phase I/II clinical study to evaluate the recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection in Chinese patients with relapsed/refractory lymphoma .
- Detailed Description
Phase Ib/II efficacy exploration and confirmation phase:
Four cohorts will be conducted in parallel to initially evaluate the recombinant humanized anti-CD47/PD-1 bifunctional anti HX009 injection.
The four cohorts in the efficacy exploration phase are:
Cohort 1: Relapsed/refractory diffuse large B-cell lymphoma; Cohort 2: relapsed/refractory peripheral T-cell lymphoma (except angioimmunoblastic T-cell lymphoma).
(except angioimmunoblastic T-cell lymphoma); Cohort 3: relapsed/refractory follicular lymphoma and relapsed/refractory marginal zone lymphoma; Cohort 4: relapsed/refractory EBV-positive non-Hodgkin's lymphoma. The study will refer to the "Guidelines for Data Monitoring Committees in Drug Clinical Trials (Trial)".
A data monitoring committee will be set up to provide continuous safety monitoring of the study and to provide advice on the dosage and dosing cycle, as well as on the follow-up of the study.
The committee will provide advice on the dosage and cycle of administration, as well as on the decision-making for subsequent extension studies.
Based on the safety data from this study at the 15 mg/kg dose level, during the efficacy exploration phase, the Each cohort will enroll 10-20 subjects, for a total of 4 cohorts, and each cohort will explore 1-2 dose levels, i.e., 10 mg/kg and 15 mg/kg, with an expected enrollment of 40-80 cases. The 10 mg/kg dose level will be enrolled first.
dose level first, and after discussion between the sponsor and the DMC, 15 mg/kg dose level will be enrolled if necessary.
The dose level of 15 mg/kg will be enrolled if necessary after discussion between the sponsor and the DMC. Based on the DMC analysis, the no-trend cohort will be enrolled in a maximum of 10 cases (with the possibility of stop enrollment midway).
The Phase II efficacy confirmation phase will select 1-2 cohorts from the 4 cohorts in the efficacy exploration phase of the study with better safety and efficacy.
1-2 indications with better efficacy to further confirm the efficacy and safety of HX009 injection. Based on the safety and efficacy data from Phase I of this study, the number of cases of subjects in the efficacy confirmation phase will be re-estimated based on statistical principles.
The number of cases of subjects in the validation phase will be re-estimated based on statistical
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 99
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description phase I dose escalation part,Phase II efficacy exploratory part and the efficacy confirmation part Recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection Phase Ib/II efficacy exploration and confirmation phase: Four cohorts will be conducted in parallel to initially evaluate the recombinant humanized anti-CD47/PD-1 bifunctional anti HX009 injection. The four cohorts in the efficacy exploration phase are: Cohort 1: Relapsed/refractory diffuse large B-cell lymphoma; Cohort 2: relapsed/refractory peripheral T-cell lymphoma (except angioimmunoblastic T-cell lymphoma). (except angioimmunoblastic T-cell lymphoma); Cohort 3: relapsed/refractory follicular lymphoma and relapsed/refractory marginal zone lymphoma; Cohort 4: relapsed/refractory EBV-positive non-Hodgkin's lymphoma.
- Primary Outcome Measures
Name Time Method Objective response rate(ORR) of patients with solid tumors treated with HX009 per Investigator Assessment Tumor assessment every 6 weeks (±7 days)，up to 1 year Objective response rate (ORR) assessed according to the evaluation criteria of each tumor type
- Secondary Outcome Measures
Name Time Method Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: Tmax Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: Tmin Approximately 1 year Key pharmacokinetic parameter
6 months and 12 months progression-free survival (PFS ) Approximately 1 year PFS is defined as the time from the start of the first dose and the first documented disease progression using RECIST 1.1 criteria or death of any cause.
Complete Remission Rate (CRR) Approximately 1 year Disappearance of all target lesions, no new lesions appearing
Duration of Remission (DOR) Tumor assessment every 6 weeks (±7 days),up to 1year The DOR is defined as the time from the first recorded response (CR or PR) to the first recorded tumor progression or death due to any cause.
Disease Control Rate (DCR) Tumor assessment every 6 weeks (±7 days),up to 1 year The DCR is defined as the percentage of participants in the analysis population who had a confirmed Complete Response, or Partial Response, or Stable Disease using RECIST 1.1 criteria.
Incidence and severity of AE and SAE, laboratory tests and vital signs（Including ：heart rate, blood pressure, respiration,temperature.）; All AEs up to 28 days after the last dose of study drug,Or other tumor treatment programs have been started (the earlier date shall prevail); irAE should be followed up to 90 days after the last dose, or other tumor treatment programs have been started Adverse events (AEs) determined by the investigator are recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE - Version 5.0).
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: Cmin Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: Cavg Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: AUCss Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: t1/2 Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: λz Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: CLss/F Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: DF Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: AUC0-t Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: Vz/F Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: AUC0-∞ Approximately 1 year Key pharmacokinetic parameter
Pharmacokinetic parameters of recombinant humanized anti-CD47/PD-1 bifunctional antibody HX009 injection: AUCext% Approximately 1 year Key pharmacokinetic parameter
Peak plasma concentration (Cmax) of HX009 in patients with relapsed/refractory lymphoma Approximately 1 year Key pharmacokinetic parameter
Antidrug antibodies (ADA) Approximately 1 year Key pharmacokinetic parameter
Neutralizing antibodies (Nab) after treatment (ADA-positive individuals only) Approximately 1 year Key pharmacokinetic parameter
Trial Locations
- Locations (1)
Cancer Hospital Chinese Academy of Medical Sciense
🇨🇳Beijing, Beijing, China