Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06038058
Other study ID # BRY812-ST-01
Secondary ID
Status Not yet recruiting
Phase Phase 1
First received
Last updated
Start date October 2023
Est. completion date December 2028

Study information

Verified date August 2023
Source BioRay Pharmaceutical Co., Ltd.
Contact He rui Yao, PhD
Phone (+86)13500018020
Email yaoherui@163.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a Phase I, multicenter, open-label, single-arm and first-in-human clinical study of BRY812 for injection. The study objectives are to evaluate the safety, tolerability, pharmacokinetic profile, anti-tumor activity and immunogenicity of BRY812 for injection in patients with advanced malignancies. Patients will receive treatment every 3 weeks until intolerable toxicity, disease progression, pregnancy, withdrawal of informed consent, death, study discontinuation, or withdrawal from the study.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 164
Est. completion date December 2028
Est. primary completion date August 2028
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - (1) Subjects who voluntarily sign the informed consent form, understand the nature, objectives, and procedure of the study and are able to complete the study according to the protocol; (2) Male or female patients, = 18 years of age (based on the date of signing the informed consent form); (3) In Phase Ia: patients must have advanced solid tumors confirmed by histopathology and/or cytology, who have failed to respond to standard-of-care (disease progression after treatment) or who could not tolerate standard-of-care, or who could not obtain effective standard-of-care or for whom there was no effective standard-of-care available; (Note: the patient population and inclusion criteria in phase Ib will be determined according to the data of phase Ia); (4) According to RECIST v1.1 (Response Evaluation Criteria in Solid Tumors), there is at least 1 measurable lesion; (5) Eastern Cooperative Oncology Group (ECOG) Status 0 to 1; (6) Adequate organ and bone marrow function (no treatment with cells, growth factors, or transfusions within 14 days prior to the first administration), as defined below: 1. Hematology: absolute neutrophil count (ANC) = 1.5 × 109/L, platelet count (PLT) = 100 × 109/L, hemoglobin (HGB) = 90 g/L; 2. Liver function: serum total bilirubin (TBIL) = 1.5 × upper limit of normal (ULN) (except for subjects with Gilbert syndrome, TBIL = 2 × ULN in patients with liver cancer or liver metastases), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN (in patients with liver cancer or liver metastases, ALT or AST = 5 × ULN); 3. Renal function: creatinine (Cr) = 1.5 × ULN or creatinine clearance (CrCL) (based on Cockcroft-Gault equation) = 60 mL/min; (7) Expected survival = 12 weeks; (8) Female subjects with fertility potential must test negative for serum human chorionic gonadotropin (HCG) before they are enrolled in the study. Female subjects with fertility potential or male subjects who have a female partner must agree to maintain no pregnancy plan and take effective contraceptive measures such as condoms from the signing of ICF to 6 months after the last dose of study drug (see Annex 1 for details); females are considered fertile from menarche to menopause (at least 12 months without menstruation) unless they are permanently infertile (through hysterectomy, bilateral salpingectomy, or bilateral oophorectomy). Exclusion Criteria: - (1) Subjects who have previous severe hypersensitivity to BRY812 or known hypersensitivity to any component or excipient of the study drug; (2) Subjects who have previously received drugs which target LIV-1; (3) Subjects who have any active infection requiring systemic therapy by intravenous infusion within 2 weeks prior to the first dose of study drug; (4) Subjects who have previous or current presence of two or more primary tumors (excluding cured cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin, and other tumors that have been stable for more than 5 years after treatment); (5) Subjects who have symptoms of active central nervous system metastases, except those with brain parenchymal metastases assessed as stable by the investigator based on the following conditions: 1. No seizures within > 12 consecutive weeks with or without the treatment of antiepileptic drugs; 2. Glucocorticoids are not required; 3. Two consecutive MRI scans (at least 4 weeks apart) show a stable state on imaging; 4. Asymptomatic inactive brain metastases are newly identified where two consecutive MRI scans (at least 4 weeks apart) show a stable state on imaging; 5. The conditions remain stable and asymptomatic for more than 1 month after treatment; (6) Subjects with serious cardiovascular and cerebrovascular diseases and lung diseases, including but not limited to: 1. Stroke, intracranial hemorrhage, unstable angina pectoris, congestive heart failure (NYHA class III-IV), myocardial infarction, severe arrhythmias (such as sustained ventricular tachycardia and ventricular fibrillation), congenital long QT syndrome, torsade de pointes, and symptomatic pulmonary embolism within 6 months before enrollment; 2. Uncontrolled hypertension (at least 2 consecutive measurements of systolic blood pressure = 160 mmHg or diastolic blood pressure = 100 mmHg); 3. Echocardiogram (ECHO) or multigated acquisition scan (MUGA) shows left ventricular ejection fraction (LVEF) < 50%; 4. During the screening period, the mean corrected (by Fridercia's formula) QT interval on three consecutive electrocardiograms is prolonged (> 450 ms in males and > 470 ms in females); 5. Subjects who have interstitial lung diseases, severe impaired lung function, severe pulmonary fibrosis, radiation pneumonitis, and other lung diseases assessed by the investigator as clinically significant; (7) Subjects who have active gastrointestinal bleeding or severe intestinal obstruction; (8) Subjects who have undergone major surgery within 4 weeks prior to the first dose of study drug or are expected to be performed during the study; (9) Subjects who have a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation; (10) Subjects who have bleeding tendency or are receiving thrombolytic or anticoagulant therapy; (11) Subjects who have used strong inhibitors or substrates of CYP3A4 and/or Pgp within 4 weeks before the first dosing or within 5 half-lives of the used drug (whichever is shorter), or who have received anti-tumor therapy or participated in other clinical studies and used other study drugs, including chemotherapy, targeted therapy, immunotherapy, biotherapy (tumor vaccines, cytokines, or growth factors for cancer control), etc.; or who have received prepared slices of Chinese crude drugs or Chinese patent medicines as anti-tumor treatment within 1 week before the first dose of study drug; (12) Subjects who have received radiation therapy, including abdominal palliative stereotactic radiotherapy, within 4 weeks prior to the first dose of study drug (non-abdominal palliative stereotactic radiotherapy within 2 weeks prior to the first dose); (13) Toxicity of previous antineoplastic therapy does not resolve to grade = 1 as defined by NCI-CTCAE v5.0 (except for asymptomatic abnormal laboratory findings considered by the investigator, such as elevated ALP, hyperuricemia, elevated blood glucose, etc.; except for toxicity with no safety risk determined by the investigator , such as alopecia, pigmentation, etc.); (14) Subjects who have been vaccinated with a live vaccine within 4 weeks before the first dose, or who intend to be vaccinated with a live vaccine during the study; (15) Subjects who have received more than 1 week of treatment with systemic corticosteroids (methylprednisolone > 10 mg/day or an equivalent dose of other similar drug) within 2 weeks prior to the first dose of study drug; (16) Subjects who have used immunosuppressants within 2 weeks prior to the first dose or once had active autoimmune diseases or had a prior history of autoimmune diseases; (17) Subjects who test positive for Hepatitis B surface antigen (HBsAg) with HBV DNA beyond the normal range; or subjects who test positive for hepatitis B core antibody with HBV DNA beyond the upper limit of normal, but do not agree to regular DNA testing during treatment and follow-up, or do not agree to receive antiviral therapy; subjects who test positive for hepatitis C virus (HCV) antibody and HCV RNA; subjects who are seropositive for human immunodeficiency virus (HIV); subjects who have syphilis and need to receive systemic treatment; (18) Subjects who have any mental or cognitive disorders that may limit their understanding and execution of the informed consent form; (19) Subjects who are pregnant or breastfeeding; (20) Subjects who plan to donate sperm after signing the informed consent form and throughout the study period, or within 6 months after the last dose of the study drug; (21)Subjects who are not eligible for enrollment or may not be able to complete the study due to other reasons by the investigator's assessment.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
BRY812 for injection
BRY812 for injection will be administered by intravenous drip, tentatively once per cycle spanning 3 weeks on D1 of each cycle until intolerable toxicity, 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.

Locations

Country Name City State
China Sun Yat-sen Memorial Hospital,Sun Yat-sen University Guangzhou Guangdong

Sponsors (1)

Lead Sponsor Collaborator
BioRay Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of adverse events An AE is any untoward medical occurrence in a patient or clinical investigational subjct administered a medicinal product and which does not necessarily have a causal relationship with this treatment. From Day 1 to 30 days after last dose; approximately 2 years
Primary Incidence of laboratory abnormalities To be summarized using descriptive statistics From Day 1 to 30 days after last dose; approximately 2 year
Primary Maximum Tolerated Dose (MTD) of BRY812 for injection Maximum Tolerated Dose (MTD) of BRY812 for injection From the first dose to the last dose;approximately 2 year
Primary Recommended phase II dose (RP2D) of BRY812 for injection Recommended phase II dose (RP2D) of BRY812 for injection From the first dose to the last dose;approximately 2 year
Primary Incidence of dose-limiting toxicity (DLT) Incidence of dose-limiting toxicity (DLT) Through 21 days after first dose
Secondary Objective response rate (ORR) ORR is defined as the proportion of patients with complete response (CR) or partial response (PR) per RECIST v1.1. Through 1 month following last dose; approximately 2 years
Secondary Progression-free survival (PFS) PFS is defined as the time from start of study treatment to first documentation of tumor progression (clinical progression or PD per RECIST v1.1). Up to approximately 3 years
Secondary Overall survival (OS) OS is defined as the time from start of study treatment to date of death due to any cause Up to approximately 3 years
Secondary Duration of response (DOR) DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (clinical progression or progressive disease (PD) per RECIST v1.1) Up to approximately 3 years
Secondary Pharmacokinetic assessment The concentrations of BRY812, total antibody and free monomethyl auristatin E (MMAE) in blood will be determined, and the following parameters will be calculated respectively. Through 18 weeks after dosing
Secondary Immunogenicity assessment The anti-drug antibody (ADA) of BRY812 in the blood is detected, and the antibody titer of ADA-positive patients is further detected according to the situation, and whether they have neutralizing antibody (NAb) is detected if necessary. Through 18 weeks after dosing
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05059522 - Continued Access Study for Participants Deriving Benefit in Pfizer-Sponsored Avelumab Parent Studies That Are Closing Phase 3
Completed NCT00948961 - A Study of CDX-1401 in Patients With Malignancies Known to Express NY-ESO-1 Phase 1/Phase 2
Completed NCT03297424 - A Study of PLX2853 in Advanced Malignancies. Phase 1
Terminated NCT02265510 - An Open-Label Study of a Novel JAK-inhibitor, INCB052793, Given to Patients With Advanced Malignancies Phase 1/Phase 2
Completed NCT03907969 - A Clinical Trial to Evaluate AZD7648 Alone and in Combination With Other Anti-cancer Agents in Patients With Advanced Cancers. Phase 1/Phase 2
Completed NCT03241173 - A Study Exploring the Safety and Efficacy of INCAGN01949 in Combination With Immune Therapies in Advanced or Metastatic Malignancies Phase 1/Phase 2
Completed NCT02923349 - A Phase 1/2, Open-Label, Dose-Escalation, Safety Study of INCAGN01949 in Subjects With Advanced or Metastatic Solid Tumors Phase 1/Phase 2
Completed NCT04025957 - A Study of SHR-1501 in Patients With Advanced Tumors Phase 1
Recruiting NCT05048134 - A Phase I Study of HRS2300 or Combined With SHR-1316 or SHR-1701 or Trametinib or Almonertinib in Patients With Advanced Malignancies Phase 1
Completed NCT00651664 - A Phase I Clinical and Pharmacodynamic Study of MLN8237, A Novel Aurora A Kinase Inhibitor, in Participants With Advanced Malignancies Phase 1
Completed NCT00611793 - PTK787/ZK222584 With Bevacizumab in Patients With Refractory and/or Advanced Malignancies Phase 1
Recruiting NCT05891171 - Study of AB598 Monotherapy and Combination Therapy in Participants With Advanced Cancers Phase 1
Not yet recruiting NCT05987605 - Clinical Study of 1A46 Drug Substance Phase 1
Terminated NCT02608268 - Phase I-Ib/II Study of MBG453 as Single Agent and in Combination With PDR001 in Patients With Advanced Malignancies Phase 1/Phase 2
Terminated NCT03277352 - INCAGN01876 in Combination With Immune Therapies in Subjects With Advanced or Metastatic Malignancies Phase 1/Phase 2
Recruiting NCT05577182 - Study of INCA32459 a LAG-3 and PD-1 Bispecific Antibody in Participants With Select Advanced Malignancies Phase 1
Completed NCT04831996 - To Evaluate the Safety, and Pharmacokinetics of Parscaclisib in Participants With Normal Renal Function and Renal Impairment. Phase 1
Recruiting NCT06468098 - A Study of IBI363 in Subjects With Advanced Malignancies Phase 1
Completed NCT02737501 - ALTA-1L Study: A Study of Brigatinib Versus Crizotinib in Anaplastic Lymphoma Kinase Positive (ALK+) Advanced Non-small Cell Lung Cancer (NSCLC) Participants Phase 3
Completed NCT03158272 - A Study of Cabiralzumab Given by Itself or With Nivolumab in Advanced Cancer or Cancer That Has Spread Phase 1