Advanced Malignancies
Conditions
Brief summary
This is a Phase I, multicenter, open-label, single-arm and first-in-human clinical study of BR111-101 for injection. The study objectives are to evaluate the safety, tolerability, pharmacokinetic profile, anti-tumor activity and immunogenicity of BR111-101 for injection in patients with advanced malignancies.
Interventions
DRUGBR111 for Injection
BR111-101 for injection will be administered by intravenous drip, disease progression, pregnancy, withdrawal of informed consent, death, study discontinuation or withdrawal from the study. The dose of each administration will be calculated based on the weight measured prior to such administration. The dosing regimen (dosing frequency and interval) for subsequent study may be adjusted based on prior data. The intravenous drip should last for ≥ 90 min for the first dose and may be adjusted to ≥ 30 min for subsequent doses if the first dose is tolerable.
Sponsors
BioRay Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Willingness to provide written informed consent for the study; 2. Age ≥ 18 years, male or female; Patients with solid tumors: Patients with histopathologically confirmed advanced solid tumors who are not amenable to surgical resection who have failed standard therapy (i.e., existing therapies with known clinical benefit) (disease progression during or after treatment) or who cannot tolerate standard therapy and are unable to obtain or refuse or have no standard therapy. Patients with lymphoma: Patients with histopathologically confirmed relapsed/refractory B-cell lymphoma who meet the 2016 WHO classification criteria and are indicated for treatment and currently have no other standard treatment as judged by the investigator. 3. All patients are required to provide tumor samples for biomarker analysis at screening. 4. ECOG score 0 to 1 . 5. Life expectancy ≥ 3 months. 6. Phase Ia dose Escalation: Patients with solid tumors or lymphoma have at least one evaluable lesion at baseline (ie, no measurable lesions) according to RECIST v1.1 or Lugano 2014 criteria; Phase Ia Safety Expansion and Phase Ib: Patients with at least 1 measurable lesion at baseline according to RECISTv1.1 and Lugano 2014 criteria. Lesions previously treated with radiotherapy or intervention should not be considered target lesions unless there is unequivocal progression. 7. Adequate organ and bone marrow function ； 8. Female patients of childbearing potential (defined as those who are not surgically sterile with hysterectomy and/or bilateral oophorectomy and are not postmenopausal, defined as having amenorrhea ≥ 12 months) must have a negative pregnancy test at entry into this study and must be non-lactating; female patients of childbearing potential or male patients with sexual partners of childbearing potential are willing to use appropriate effective contraceptive measures such as abstinence and double-barrier methods (e.g., condom plus diaphragm), oral contraceptives, and placement of an intrauterine device during the study and for 6 months after the last investigational product. 9. Able to understand trial requirements and willing and able to comply with trial and follow-up procedures.
Exclusion criteria
Patients will not be eligible to participate in the study if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of BR111 if any (for dose escalation part) | About 9 months | Participants will receive BR111 for injection once every three weeks. The MTD will be determined by the number of participants who experience a dose limiting toxicity (DLT). |
| Recommended Phase 2 Dose(RP2D) of BR111 (for dose escalation part) | About 9 months | The selection of RP2D will be based on consideration of overall safety information together with available pharmacokinetic, pharmacodynamic, and efficacy data. The RP2D may be the MTD or may be a lower dose within the tolerable dose range. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of anti-drug antibodies (ADA) | Until 30 days since the last dose of investigational product or until initiation of a new anti-cancer treatment, whichever occurs first | — |
| Incidence of Neutralizing antibodies (Nab) | Until 30 days since the last dose of investigational product or until initiation of a new anti-cancer treatment, whichever occurs first | — |
| Concentration of BR111 total antibody, prodrug and the free cytotoxin | Until 30 days since the last dose of investigational product or until initiation of a new anti-cancer treatment, whichever occurs first | — |
| objective response rate（ORR） | Until 30 days since the last dose of investigational product or until initiation of a new anti-cancer treatment, whichever occurs first | Objective Response Rate is defined as the percentage of patients with a complete response (CR) or partial response (PR) |
Countries
China
Contacts
Primary ContactZhimin Shao, Doctoral Degree
Backup ContactJian Zhang, Doctoral Degree
Outcome results
None listed